Neil Osterweil

BOSTON – Urine-based screening for tuberculosis added to standard sputum-based screening can reduce the risk of TB-associated deaths among hospitalized patients with advanced HIV compared with sputum-based screening alone, results of a randomized trial indicate.

Among 2,574 hospitalized HIV-positive patients, the rate of death at 56 days, the primary endpoint, was 21.1% for patients screened with standard-of-care sputum testing using the Xpert MTB/RIF assay, compared with 18.3% for patients screened with sputum testing and urine-sample testing by the Xpert MTB/RIF and the Determine TB-LAM urine dipstick test, reported Ankur Gupta-Wright, MBBS, MRCP, from the London School of Hygiene and Tropical Medicine.

“The findings our trial support the use of urine-based TB screening, and we hope to change how we screen for TB in HIV-positive admissions in the hospital in places with high burden of HIV and TB,” he said, speaking on behalf of colleagues in the STAMP Study.

HIV-related TB caused an estimated 400,000 deaths worldwide in 2016, and is responsible for between 32% and 67% of deaths in HIV-positive adults admit to hospitals in Africa. Yet half of all of those cases of TB are undiagnosed at the time of death, he said.

Urine based screens are easily obtained and have good diagnostic yield for disseminated TB, which is common in patients with advanced HIV, he said.

To see whether adding urine screening could increase TB diagnosis and treatment and reduce TB deaths among hospitalized HIV+ patients, the investigators enrolled 2,600 unselected HIV+ adults admitted to hospitals in South Africa and Malawi. Patients less than 18 years of age, those who had been treated for TB with the last 12 months or had received TB prophylaxis with isoniazid within the last 6 months were excluded, leaving a sample size of 2,574.

The patients were randomly assigned to standard-of-care Xpert MTB/RIF sputum screening either alone or with the addition of the two urine-based screens already described.

The overall absolute difference in risk of death at 56 days was -2.8% favoring urine screening (P = .074). As noted, this difference was only significant among patients with CD4 counts below 100/uL. Among these patients, mortality rates for nonurine screened versus screened were 35.7% vs. 28.8%, respectively (P = .036).

Baseline hemoglobin below 8 g/dl and TB suspected at admission were also predictive of better outcomes with the addition of urine-based screening.

An analysis of time to death stratified by baseline CD4 cell count also showed the advantage of urine screening for the sickest patients, with an adjusted hazard ratio for patients with CD4 counts below 100 of 0.77 (P = .047).

The urine-based screening also lead to significantly more microbiologically confirmed and clinically diagnosed TB, and more TB treatment (P less than .001 for each).

A separate cost analysis, presented in a scientific poster (CROI 2018 Abstract 1117LB), showed that the incremental cost-effectiveness ratios for the urine-based intervention were $490 per year of life save in Malawi, and $850 per year of life saved in South Africa.

The study was funded by UK AID, the UK Medical Research Council, and the Wellcome Trust. Dr. Gupta-Wright reported having no conflicts of interest to disclose.

SOURCE: Gupta-Wright, A et al. CROI 2018, Abstract 38LB.

BOSTON – Urine-based screening for tuberculosis added to standard sputum-based screening can reduce the risk of TB-associated deaths among hospitalized patients with advanced HIV compared with sputum-based screening alone, results of a randomized trial indicate.

Among 2,574 hospitalized HIV-positive patients, the rate of death at 56 days, the primary endpoint, was 21.1% for patients screened with standard-of-care sputum testing using the Xpert MTB/RIF assay, compared with 18.3% for patients screened with sputum testing and urine-sample testing by the Xpert MTB/RIF and the Determine TB-LAM urine dipstick test, reported Ankur Gupta-Wright, MBBS, MRCP, from the London School of Hygiene and Tropical Medicine.

“The findings our trial support the use of urine-based TB screening, and we hope to change how we screen for TB in HIV-positive admissions in the hospital in places with high burden of HIV and TB,” he said, speaking on behalf of colleagues in the STAMP Study.

HIV-related TB caused an estimated 400,000 deaths worldwide in 2016, and is responsible for between 32% and 67% of deaths in HIV-positive adults admit to hospitals in Africa. Yet half of all of those cases of TB are undiagnosed at the time of death, he said.

Urine based screens are easily obtained and have good diagnostic yield for disseminated TB, which is common in patients with advanced HIV, he said.

To see whether adding urine screening could increase TB diagnosis and treatment and reduce TB deaths among hospitalized HIV+ patients, the investigators enrolled 2,600 unselected HIV+ adults admitted to hospitals in South Africa and Malawi. Patients less than 18 years of age, those who had been treated for TB with the last 12 months or had received TB prophylaxis with isoniazid within the last 6 months were excluded, leaving a sample size of 2,574.

The patients were randomly assigned to standard-of-care Xpert MTB/RIF sputum screening either alone or with the addition of the two urine-based screens already described.

The overall absolute difference in risk of death at 56 days was -2.8% favoring urine screening (P = .074). As noted, this difference was only significant among patients with CD4 counts below 100/uL. Among these patients, mortality rates for nonurine screened versus screened were 35.7% vs. 28.8%, respectively (P = .036).

Baseline hemoglobin below 8 g/dl and TB suspected at admission were also predictive of better outcomes with the addition of urine-based screening.

An analysis of time to death stratified by baseline CD4 cell count also showed the advantage of urine screening for the sickest patients, with an adjusted hazard ratio for patients with CD4 counts below 100 of 0.77 (P = .047).

The urine-based screening also lead to significantly more microbiologically confirmed and clinically diagnosed TB, and more TB treatment (P less than .001 for each).

A separate cost analysis, presented in a scientific poster (CROI 2018 Abstract 1117LB), showed that the incremental cost-effectiveness ratios for the urine-based intervention were $490 per year of life save in Malawi, and $850 per year of life saved in South Africa.

The study was funded by UK AID, the UK Medical Research Council, and the Wellcome Trust. Dr. Gupta-Wright reported having no conflicts of interest to disclose.

SOURCE: Gupta-Wright, A et al. CROI 2018, Abstract 38LB.

BOSTON – Urine-based screening for tuberculosis added to standard sputum-based screening can reduce the risk of TB-associated deaths among hospitalized patients with advanced HIV compared with sputum-based screening alone, results of a randomized trial indicate.

Among 2,574 hospitalized HIV-positive patients, the rate of death at 56 days, the primary endpoint, was 21.1% for patients screened with standard-of-care sputum testing using the Xpert MTB/RIF assay, compared with 18.3% for patients screened with sputum testing and urine-sample testing by the Xpert MTB/RIF and the Determine TB-LAM urine dipstick test, reported Ankur Gupta-Wright, MBBS, MRCP, from the London School of Hygiene and Tropical Medicine.

“The findings our trial support the use of urine-based TB screening, and we hope to change how we screen for TB in HIV-positive admissions in the hospital in places with high burden of HIV and TB,” he said, speaking on behalf of colleagues in the STAMP Study.

HIV-related TB caused an estimated 400,000 deaths worldwide in 2016, and is responsible for between 32% and 67% of deaths in HIV-positive adults admit to hospitals in Africa. Yet half of all of those cases of TB are undiagnosed at the time of death, he said.

Urine based screens are easily obtained and have good diagnostic yield for disseminated TB, which is common in patients with advanced HIV, he said.

To see whether adding urine screening could increase TB diagnosis and treatment and reduce TB deaths among hospitalized HIV+ patients, the investigators enrolled 2,600 unselected HIV+ adults admitted to hospitals in South Africa and Malawi. Patients less than 18 years of age, those who had been treated for TB with the last 12 months or had received TB prophylaxis with isoniazid within the last 6 months were excluded, leaving a sample size of 2,574.

The patients were randomly assigned to standard-of-care Xpert MTB/RIF sputum screening either alone or with the addition of the two urine-based screens already described.

The overall absolute difference in risk of death at 56 days was -2.8% favoring urine screening (P = .074). As noted, this difference was only significant among patients with CD4 counts below 100/uL. Among these patients, mortality rates for nonurine screened versus screened were 35.7% vs. 28.8%, respectively (P = .036).

Baseline hemoglobin below 8 g/dl and TB suspected at admission were also predictive of better outcomes with the addition of urine-based screening.

An analysis of time to death stratified by baseline CD4 cell count also showed the advantage of urine screening for the sickest patients, with an adjusted hazard ratio for patients with CD4 counts below 100 of 0.77 (P = .047).

The urine-based screening also lead to significantly more microbiologically confirmed and clinically diagnosed TB, and more TB treatment (P less than .001 for each).

A separate cost analysis, presented in a scientific poster (CROI 2018 Abstract 1117LB), showed that the incremental cost-effectiveness ratios for the urine-based intervention were $490 per year of life save in Malawi, and $850 per year of life saved in South Africa.

The study was funded by UK AID, the UK Medical Research Council, and the Wellcome Trust. Dr. Gupta-Wright reported having no conflicts of interest to disclose.

SOURCE: Gupta-Wright, A et al. CROI 2018, Abstract 38LB.

LA JOLLA, CALIF. – When patients with peripheral T-cell lymphoma (PTCL) experience relapse, consider an allogeneic stem cell transplant or clinical trial, investigators advised.

Patients with relapsed PTCL have generally dismal outcomes, with a median progression-free survival (PFS) of 3.7 months and a median overall survival (OS) of just 6.5 months, according to one study (J Clin Oncol. 2013 Jun 1;31[16]:1970-6).

Courtesy Larry Young

She outlined her center’s approach for treating patients with relapsed or refractory PTCL, following a case presentation by Royal Marsden fellow Matthew Cross, MD.

Complex disease, multiple therapies

The patient was a 71-year-old woman who in 2007 had a diagnosis of asymptomatic stage 4A follicular lymphoma managed with observation; in 2010, she was diagnosed with a CD30-positive PTCL not otherwise specified with ongoing low-level bone marrow involvement with follicular lymphoma.

She initially was treated elsewhere with R-CHOP chemotherapy (cyclophosphamide, doxorubicin, vincristine, and prednisone plus rituximab) and had a response after four cycles; however, she had progression with new intra-abdominal nodal sites by the sixth cycle and then was started on two cycles of ESHAP (etoposide, methylprednisolone, high-dose cytarabine, and cisplatin), but she had further progression by May 2011 and opted to forgo additional treatment.

By July 2011, however, she became highly symptomatic with new pruritic rashes on her legs, abdominal pain, and distention. She was referred to the Royal Marsden Hospital, where she was eventually diagnosed with angioimmunoblastic T-cell lymphoma (AITL) with an Epstein-Barr virus–negative clonal large B-cell proliferation in her bone marrow.

She was treated with gemcitabine plus methylprednisolone and prophylactic intrathecal methotrexate and had an “excellent clinical and radiological response,” Dr. Cross said.

A subsequent bone marrow biopsy showed marked hypocellularity but no evidence of either T-cell of B-cell lymphomas.

An autologous stem cell transplant was planned, but two attempts at harvesting peripheral blood stem cells – including one with plerixafor (Mozobil) – failed, and a PET scan within 3 months showed signs of early progression.

In April 2012, the patient was started on romidepsin (Istodax) and had a 1-year remission. But in April 2013, a repeat biopsy again showed CD30-positive AITL. Based on the CD30 positivity, the patient was started on brentuximab vedotin (Adcetris) in May 2013. She was observed to have progression in inguinal nodes in January 2014; she was treated with local radiotherapy and continued on brentuximab but had further progression in June 2014. At that time, she had additional gemcitabine-based combination chemotherapy and had stable disease for 10 months.

In March 2015, she received lenalidomide for further progression but could not tolerate the drug. She died in September 2015, 5 years after diagnosis and 4.5 years after frontline therapy failed.

Therapeutic rationale

Dr. Dearden walked through the choices that she, along with Dr. Cross and their colleagues, made in treating the patient. They chose gemcitabine-based regimens for salvage therapy because of the drug’s efficacy across various forms on non-Hodgkin and Hodgkin lymphoma, she said.

However, a randomized, phase 3, noninferiority trial in the United Kingdom comparing GEM-P (gemcitabine, cisplatin, and methylprednisolone) with CHOP for first-line therapy of PTCL was halted at the interim analysis because GEM-P had not meet the primary endpoint, she said. Results of that trial have not been published to date.

“Clearly, if it’s the patients who do well, often it’s because they achieve a good enough remission to be able to proceed to some sort of consolidation therapy with autologous or allogeneic stem cell transplants, and I think auto-graft is probably accepted for the younger, fitter patients with relapsed chemo-sensitive disease,” she said.

Three-year survival rates for autologous hematopoietic stem cell transplantation range from 36% to 58% and are better than those seen with chemotherapy alone, she said.

“The problem of course is that not many patients receive the planned auto-graft, even if that’s the intention, either because of failure to respond to salvage regimen or early disease progression, which happens before the transplant is able to take place,” she said,

A reasonable alternative for patients with relapsed/refractory PTCL is allogeneic transplantation, as shown in a 2008 study.

Among 77 patients – 57 of whom had received myeloablative conditioning, 31 of whom were in complete remission, and 26 of whom had partial response at the time of transplants – the 5-year treatment-related mortality rate was 33%. However, the 5-year event-free and overall survival rates were 53% and 57%, respectively. Patients with AITL had especially good outcomes (J Clin Oncol. 2008 May 10;26[14]:2264-71).

“In an ideal world, if our patient had been a suitable candidate for an allo-transplant, it’s what we would have tried to undertake,” Dr. Dearden said.

Dr. Dearden recommended that all patients with relapsed or refractory PTCL be considered for clinical trials. For fit patients in first relapse, combination platinum-based chemotherapy followed by autologous or allogeneic transplant may be effective.

For patients not eligible for transplant or with chemotherapy-refractory disease, she recommended trying the following monotherapy approaches: pralatrexate for patients with PTCL not otherwise specified, histone deacetylase inhibitors or 5-azacytidine for AITL, brentuximab vedotin for anaplastic large cell lymphoma, and pembrolizumab for natural killer/T-cell lymphomas.

Although two lines of intensive chemotherapy had failed the case patient within 6 months of diagnosis, she still survived for 5 years with sequential monotherapies, Dr. Dearden noted.

“I use to say to her, ‘You just need to stay one drug ahead of your disease.’ And she was well, she had a very good quality of life for a period of time, and if you can deliver a treatment that is effective for a patient, it will extend their survival,” Dr. Dearden said.

The T-cell Lymphoma Forum is held by Jonathan Wood & Associates, which is owned by the same company as this news organization. Dr. Dearden has consulted for MedImmune, Infinity Pharmaceuticals, Janssen, Gilead Sciences, and Roche, and has received honoraria from Janssen and Gilead. Dr. Cross reported no having no financial disclosures.

LA JOLLA, CALIF. – When patients with peripheral T-cell lymphoma (PTCL) experience relapse, consider an allogeneic stem cell transplant or clinical trial, investigators advised.

Patients with relapsed PTCL have generally dismal outcomes, with a median progression-free survival (PFS) of 3.7 months and a median overall survival (OS) of just 6.5 months, according to one study (J Clin Oncol. 2013 Jun 1;31[16]:1970-6).

Courtesy Larry Young

She outlined her center’s approach for treating patients with relapsed or refractory PTCL, following a case presentation by Royal Marsden fellow Matthew Cross, MD.

Complex disease, multiple therapies

The patient was a 71-year-old woman who in 2007 had a diagnosis of asymptomatic stage 4A follicular lymphoma managed with observation; in 2010, she was diagnosed with a CD30-positive PTCL not otherwise specified with ongoing low-level bone marrow involvement with follicular lymphoma.

She initially was treated elsewhere with R-CHOP chemotherapy (cyclophosphamide, doxorubicin, vincristine, and prednisone plus rituximab) and had a response after four cycles; however, she had progression with new intra-abdominal nodal sites by the sixth cycle and then was started on two cycles of ESHAP (etoposide, methylprednisolone, high-dose cytarabine, and cisplatin), but she had further progression by May 2011 and opted to forgo additional treatment.

By July 2011, however, she became highly symptomatic with new pruritic rashes on her legs, abdominal pain, and distention. She was referred to the Royal Marsden Hospital, where she was eventually diagnosed with angioimmunoblastic T-cell lymphoma (AITL) with an Epstein-Barr virus–negative clonal large B-cell proliferation in her bone marrow.

She was treated with gemcitabine plus methylprednisolone and prophylactic intrathecal methotrexate and had an “excellent clinical and radiological response,” Dr. Cross said.

A subsequent bone marrow biopsy showed marked hypocellularity but no evidence of either T-cell of B-cell lymphomas.

An autologous stem cell transplant was planned, but two attempts at harvesting peripheral blood stem cells – including one with plerixafor (Mozobil) – failed, and a PET scan within 3 months showed signs of early progression.

In April 2012, the patient was started on romidepsin (Istodax) and had a 1-year remission. But in April 2013, a repeat biopsy again showed CD30-positive AITL. Based on the CD30 positivity, the patient was started on brentuximab vedotin (Adcetris) in May 2013. She was observed to have progression in inguinal nodes in January 2014; she was treated with local radiotherapy and continued on brentuximab but had further progression in June 2014. At that time, she had additional gemcitabine-based combination chemotherapy and had stable disease for 10 months.

In March 2015, she received lenalidomide for further progression but could not tolerate the drug. She died in September 2015, 5 years after diagnosis and 4.5 years after frontline therapy failed.

Therapeutic rationale

Dr. Dearden walked through the choices that she, along with Dr. Cross and their colleagues, made in treating the patient. They chose gemcitabine-based regimens for salvage therapy because of the drug’s efficacy across various forms on non-Hodgkin and Hodgkin lymphoma, she said.

However, a randomized, phase 3, noninferiority trial in the United Kingdom comparing GEM-P (gemcitabine, cisplatin, and methylprednisolone) with CHOP for first-line therapy of PTCL was halted at the interim analysis because GEM-P had not meet the primary endpoint, she said. Results of that trial have not been published to date.

“Clearly, if it’s the patients who do well, often it’s because they achieve a good enough remission to be able to proceed to some sort of consolidation therapy with autologous or allogeneic stem cell transplants, and I think auto-graft is probably accepted for the younger, fitter patients with relapsed chemo-sensitive disease,” she said.

Three-year survival rates for autologous hematopoietic stem cell transplantation range from 36% to 58% and are better than those seen with chemotherapy alone, she said.

“The problem of course is that not many patients receive the planned auto-graft, even if that’s the intention, either because of failure to respond to salvage regimen or early disease progression, which happens before the transplant is able to take place,” she said,

A reasonable alternative for patients with relapsed/refractory PTCL is allogeneic transplantation, as shown in a 2008 study.

Among 77 patients – 57 of whom had received myeloablative conditioning, 31 of whom were in complete remission, and 26 of whom had partial response at the time of transplants – the 5-year treatment-related mortality rate was 33%. However, the 5-year event-free and overall survival rates were 53% and 57%, respectively. Patients with AITL had especially good outcomes (J Clin Oncol. 2008 May 10;26[14]:2264-71).

“In an ideal world, if our patient had been a suitable candidate for an allo-transplant, it’s what we would have tried to undertake,” Dr. Dearden said.

Dr. Dearden recommended that all patients with relapsed or refractory PTCL be considered for clinical trials. For fit patients in first relapse, combination platinum-based chemotherapy followed by autologous or allogeneic transplant may be effective.

For patients not eligible for transplant or with chemotherapy-refractory disease, she recommended trying the following monotherapy approaches: pralatrexate for patients with PTCL not otherwise specified, histone deacetylase inhibitors or 5-azacytidine for AITL, brentuximab vedotin for anaplastic large cell lymphoma, and pembrolizumab for natural killer/T-cell lymphomas.

Although two lines of intensive chemotherapy had failed the case patient within 6 months of diagnosis, she still survived for 5 years with sequential monotherapies, Dr. Dearden noted.

“I use to say to her, ‘You just need to stay one drug ahead of your disease.’ And she was well, she had a very good quality of life for a period of time, and if you can deliver a treatment that is effective for a patient, it will extend their survival,” Dr. Dearden said.

The T-cell Lymphoma Forum is held by Jonathan Wood & Associates, which is owned by the same company as this news organization. Dr. Dearden has consulted for MedImmune, Infinity Pharmaceuticals, Janssen, Gilead Sciences, and Roche, and has received honoraria from Janssen and Gilead. Dr. Cross reported no having no financial disclosures.

LA JOLLA, CALIF. – When patients with peripheral T-cell lymphoma (PTCL) experience relapse, consider an allogeneic stem cell transplant or clinical trial, investigators advised.

Patients with relapsed PTCL have generally dismal outcomes, with a median progression-free survival (PFS) of 3.7 months and a median overall survival (OS) of just 6.5 months, according to one study (J Clin Oncol. 2013 Jun 1;31[16]:1970-6).

Courtesy Larry Young

She outlined her center’s approach for treating patients with relapsed or refractory PTCL, following a case presentation by Royal Marsden fellow Matthew Cross, MD.

Complex disease, multiple therapies

The patient was a 71-year-old woman who in 2007 had a diagnosis of asymptomatic stage 4A follicular lymphoma managed with observation; in 2010, she was diagnosed with a CD30-positive PTCL not otherwise specified with ongoing low-level bone marrow involvement with follicular lymphoma.

She initially was treated elsewhere with R-CHOP chemotherapy (cyclophosphamide, doxorubicin, vincristine, and prednisone plus rituximab) and had a response after four cycles; however, she had progression with new intra-abdominal nodal sites by the sixth cycle and then was started on two cycles of ESHAP (etoposide, methylprednisolone, high-dose cytarabine, and cisplatin), but she had further progression by May 2011 and opted to forgo additional treatment.

By July 2011, however, she became highly symptomatic with new pruritic rashes on her legs, abdominal pain, and distention. She was referred to the Royal Marsden Hospital, where she was eventually diagnosed with angioimmunoblastic T-cell lymphoma (AITL) with an Epstein-Barr virus–negative clonal large B-cell proliferation in her bone marrow.

She was treated with gemcitabine plus methylprednisolone and prophylactic intrathecal methotrexate and had an “excellent clinical and radiological response,” Dr. Cross said.

A subsequent bone marrow biopsy showed marked hypocellularity but no evidence of either T-cell of B-cell lymphomas.

An autologous stem cell transplant was planned, but two attempts at harvesting peripheral blood stem cells – including one with plerixafor (Mozobil) – failed, and a PET scan within 3 months showed signs of early progression.

In April 2012, the patient was started on romidepsin (Istodax) and had a 1-year remission. But in April 2013, a repeat biopsy again showed CD30-positive AITL. Based on the CD30 positivity, the patient was started on brentuximab vedotin (Adcetris) in May 2013. She was observed to have progression in inguinal nodes in January 2014; she was treated with local radiotherapy and continued on brentuximab but had further progression in June 2014. At that time, she had additional gemcitabine-based combination chemotherapy and had stable disease for 10 months.

In March 2015, she received lenalidomide for further progression but could not tolerate the drug. She died in September 2015, 5 years after diagnosis and 4.5 years after frontline therapy failed.

Therapeutic rationale

Dr. Dearden walked through the choices that she, along with Dr. Cross and their colleagues, made in treating the patient. They chose gemcitabine-based regimens for salvage therapy because of the drug’s efficacy across various forms on non-Hodgkin and Hodgkin lymphoma, she said.

However, a randomized, phase 3, noninferiority trial in the United Kingdom comparing GEM-P (gemcitabine, cisplatin, and methylprednisolone) with CHOP for first-line therapy of PTCL was halted at the interim analysis because GEM-P had not meet the primary endpoint, she said. Results of that trial have not been published to date.

“Clearly, if it’s the patients who do well, often it’s because they achieve a good enough remission to be able to proceed to some sort of consolidation therapy with autologous or allogeneic stem cell transplants, and I think auto-graft is probably accepted for the younger, fitter patients with relapsed chemo-sensitive disease,” she said.

Three-year survival rates for autologous hematopoietic stem cell transplantation range from 36% to 58% and are better than those seen with chemotherapy alone, she said.

“The problem of course is that not many patients receive the planned auto-graft, even if that’s the intention, either because of failure to respond to salvage regimen or early disease progression, which happens before the transplant is able to take place,” she said,

A reasonable alternative for patients with relapsed/refractory PTCL is allogeneic transplantation, as shown in a 2008 study.

Among 77 patients – 57 of whom had received myeloablative conditioning, 31 of whom were in complete remission, and 26 of whom had partial response at the time of transplants – the 5-year treatment-related mortality rate was 33%. However, the 5-year event-free and overall survival rates were 53% and 57%, respectively. Patients with AITL had especially good outcomes (J Clin Oncol. 2008 May 10;26[14]:2264-71).

“In an ideal world, if our patient had been a suitable candidate for an allo-transplant, it’s what we would have tried to undertake,” Dr. Dearden said.

Dr. Dearden recommended that all patients with relapsed or refractory PTCL be considered for clinical trials. For fit patients in first relapse, combination platinum-based chemotherapy followed by autologous or allogeneic transplant may be effective.

For patients not eligible for transplant or with chemotherapy-refractory disease, she recommended trying the following monotherapy approaches: pralatrexate for patients with PTCL not otherwise specified, histone deacetylase inhibitors or 5-azacytidine for AITL, brentuximab vedotin for anaplastic large cell lymphoma, and pembrolizumab for natural killer/T-cell lymphomas.

Although two lines of intensive chemotherapy had failed the case patient within 6 months of diagnosis, she still survived for 5 years with sequential monotherapies, Dr. Dearden noted.

“I use to say to her, ‘You just need to stay one drug ahead of your disease.’ And she was well, she had a very good quality of life for a period of time, and if you can deliver a treatment that is effective for a patient, it will extend their survival,” Dr. Dearden said.

The T-cell Lymphoma Forum is held by Jonathan Wood & Associates, which is owned by the same company as this news organization. Dr. Dearden has consulted for MedImmune, Infinity Pharmaceuticals, Janssen, Gilead Sciences, and Roche, and has received honoraria from Janssen and Gilead. Dr. Cross reported no having no financial disclosures.

BOSTON – Prisoners living with HIV who have drug- or alcohol-abuse disorders and are given extended-release naltrexone prior to release are significantly more likely to have improved viral suppression at 6 months, compared with fellow HIV+ prisoners who do not, investigators in two parallel clinical trials reported.

“A medication that can be used for reduction of alcohol and opiate use could also help stabilize patients coming out of prison and jail, and help maintain or achieve viral suppression,” said Sandra Springer, MD, from Yale University, New Haven, Conn.

Neil Osterweil/Frontline Medical News

Dr. Springer and her colleagues had shown in a previous study that, although 59% of HIV-positive prisoners treated with ART while incarcerated attained viral suppression, the percentage who retained suppression dropped to 18% just 3 months after they were released. The investigators also found that relapse to drug and alcohol use occurs quickly after release, and that relapses are associated with loss of viral suppression.

In the studies reported at CROI 2018, Dr. Springer and her colleagues evaluated the effects of treatment with XR-NTX on HIV viral suppression among HIV-positive prisoners and jail detainees with either opioid-use disorders (NEW HOPE study) or alcohol-use disorders (INSPIRE study) after they are released to the community.

Both studies were double-blind, placebo-controlled, randomized trials. Detainees were recruited, enrolled, and randomized while imprisoned to receive either placebo or XR-NTX in six monthly injections, with the first performed in prison, and the subsequent five injections performed in the community.

The participants were all HIV-seropositive prisoners aged 18 years or older returning to communities in Connecticut and western Massachusetts who met DSM-IV criteria for either alcohol- or opioid-use disorder.

The investigators found that among opioid users in NEW HOPE, viral suppression levels (fewer than 50 copies/mL) improved from 37.9% at baseline to 60.6% at 6 months among 66 individuals who received XR-NTX (P = .002). In contrast, viral suppression among 27 placebo users dropped from 55.6% at baseline to 40.7%, although this decline was not statistically significant.

In multivariate analysis controlling for treatment arm, cocaine-use disorder, homelessness, or number of injections received, the only significant predictor for viral suppression at 6 months was XR-NTX vs. placebo (odds ratio, 2.90; P = .043). There were no serious adverse events in this study.

Among those with alcohol-use disorders in the INSPIRE study, the changes in viral suppression were similar to those in the NEW HOPE study, improving from 31% at baseline to 56.7% at 6 months among 67 participants in the XR-NTX arm (P = .001), compared with a decline from 42% to 30.3% among 33 participants in the placebo arm, although again this difference was not significant.

In the INSPIRE study, significant predictors of viral suppression at 6 months included naltrexone XR (OR, 4.54; P = .009), three or more injections (OR, 6.34; P = .001), white vs. black or Hispanic (OR, 5.37; P = .040), and alcohol improvement score, a composite measure of drinking parameters (OR, 1.43; P =.033).

Dr. Springer said in the briefing that inclusion criteria in the studies were broad enough to allow overlap between alcohol-use and drug-use disorders,

She emphasized that persons living with HIV who have drug- or alcohol-use disorders and are being released from incarcerations should be strongly considered for antiopioid and/or antialcohol pharmacotherapy in addition to ART.

The study was supported by National Institutes of Health grants, and by Alkermes, which supplied XR-NTX and placebo to investigators. Dr. Springer disclosed research grants from the National Institute on Drug Abuse.

SOURCE: Springer S et al. CROI Abstract 96

BOSTON – Prisoners living with HIV who have drug- or alcohol-abuse disorders and are given extended-release naltrexone prior to release are significantly more likely to have improved viral suppression at 6 months, compared with fellow HIV+ prisoners who do not, investigators in two parallel clinical trials reported.

“A medication that can be used for reduction of alcohol and opiate use could also help stabilize patients coming out of prison and jail, and help maintain or achieve viral suppression,” said Sandra Springer, MD, from Yale University, New Haven, Conn.

Neil Osterweil/Frontline Medical News

Dr. Springer and her colleagues had shown in a previous study that, although 59% of HIV-positive prisoners treated with ART while incarcerated attained viral suppression, the percentage who retained suppression dropped to 18% just 3 months after they were released. The investigators also found that relapse to drug and alcohol use occurs quickly after release, and that relapses are associated with loss of viral suppression.

In the studies reported at CROI 2018, Dr. Springer and her colleagues evaluated the effects of treatment with XR-NTX on HIV viral suppression among HIV-positive prisoners and jail detainees with either opioid-use disorders (NEW HOPE study) or alcohol-use disorders (INSPIRE study) after they are released to the community.

Both studies were double-blind, placebo-controlled, randomized trials. Detainees were recruited, enrolled, and randomized while imprisoned to receive either placebo or XR-NTX in six monthly injections, with the first performed in prison, and the subsequent five injections performed in the community.

The participants were all HIV-seropositive prisoners aged 18 years or older returning to communities in Connecticut and western Massachusetts who met DSM-IV criteria for either alcohol- or opioid-use disorder.

The investigators found that among opioid users in NEW HOPE, viral suppression levels (fewer than 50 copies/mL) improved from 37.9% at baseline to 60.6% at 6 months among 66 individuals who received XR-NTX (P = .002). In contrast, viral suppression among 27 placebo users dropped from 55.6% at baseline to 40.7%, although this decline was not statistically significant.

In multivariate analysis controlling for treatment arm, cocaine-use disorder, homelessness, or number of injections received, the only significant predictor for viral suppression at 6 months was XR-NTX vs. placebo (odds ratio, 2.90; P = .043). There were no serious adverse events in this study.

Among those with alcohol-use disorders in the INSPIRE study, the changes in viral suppression were similar to those in the NEW HOPE study, improving from 31% at baseline to 56.7% at 6 months among 67 participants in the XR-NTX arm (P = .001), compared with a decline from 42% to 30.3% among 33 participants in the placebo arm, although again this difference was not significant.

In the INSPIRE study, significant predictors of viral suppression at 6 months included naltrexone XR (OR, 4.54; P = .009), three or more injections (OR, 6.34; P = .001), white vs. black or Hispanic (OR, 5.37; P = .040), and alcohol improvement score, a composite measure of drinking parameters (OR, 1.43; P =.033).

Dr. Springer said in the briefing that inclusion criteria in the studies were broad enough to allow overlap between alcohol-use and drug-use disorders,

She emphasized that persons living with HIV who have drug- or alcohol-use disorders and are being released from incarcerations should be strongly considered for antiopioid and/or antialcohol pharmacotherapy in addition to ART.

The study was supported by National Institutes of Health grants, and by Alkermes, which supplied XR-NTX and placebo to investigators. Dr. Springer disclosed research grants from the National Institute on Drug Abuse.

SOURCE: Springer S et al. CROI Abstract 96

BOSTON – Prisoners living with HIV who have drug- or alcohol-abuse disorders and are given extended-release naltrexone prior to release are significantly more likely to have improved viral suppression at 6 months, compared with fellow HIV+ prisoners who do not, investigators in two parallel clinical trials reported.

“A medication that can be used for reduction of alcohol and opiate use could also help stabilize patients coming out of prison and jail, and help maintain or achieve viral suppression,” said Sandra Springer, MD, from Yale University, New Haven, Conn.

Neil Osterweil/Frontline Medical News

Dr. Springer and her colleagues had shown in a previous study that, although 59% of HIV-positive prisoners treated with ART while incarcerated attained viral suppression, the percentage who retained suppression dropped to 18% just 3 months after they were released. The investigators also found that relapse to drug and alcohol use occurs quickly after release, and that relapses are associated with loss of viral suppression.

In the studies reported at CROI 2018, Dr. Springer and her colleagues evaluated the effects of treatment with XR-NTX on HIV viral suppression among HIV-positive prisoners and jail detainees with either opioid-use disorders (NEW HOPE study) or alcohol-use disorders (INSPIRE study) after they are released to the community.

Both studies were double-blind, placebo-controlled, randomized trials. Detainees were recruited, enrolled, and randomized while imprisoned to receive either placebo or XR-NTX in six monthly injections, with the first performed in prison, and the subsequent five injections performed in the community.

The participants were all HIV-seropositive prisoners aged 18 years or older returning to communities in Connecticut and western Massachusetts who met DSM-IV criteria for either alcohol- or opioid-use disorder.

The investigators found that among opioid users in NEW HOPE, viral suppression levels (fewer than 50 copies/mL) improved from 37.9% at baseline to 60.6% at 6 months among 66 individuals who received XR-NTX (P = .002). In contrast, viral suppression among 27 placebo users dropped from 55.6% at baseline to 40.7%, although this decline was not statistically significant.

In multivariate analysis controlling for treatment arm, cocaine-use disorder, homelessness, or number of injections received, the only significant predictor for viral suppression at 6 months was XR-NTX vs. placebo (odds ratio, 2.90; P = .043). There were no serious adverse events in this study.

Among those with alcohol-use disorders in the INSPIRE study, the changes in viral suppression were similar to those in the NEW HOPE study, improving from 31% at baseline to 56.7% at 6 months among 67 participants in the XR-NTX arm (P = .001), compared with a decline from 42% to 30.3% among 33 participants in the placebo arm, although again this difference was not significant.

In the INSPIRE study, significant predictors of viral suppression at 6 months included naltrexone XR (OR, 4.54; P = .009), three or more injections (OR, 6.34; P = .001), white vs. black or Hispanic (OR, 5.37; P = .040), and alcohol improvement score, a composite measure of drinking parameters (OR, 1.43; P =.033).

Dr. Springer said in the briefing that inclusion criteria in the studies were broad enough to allow overlap between alcohol-use and drug-use disorders,

She emphasized that persons living with HIV who have drug- or alcohol-use disorders and are being released from incarcerations should be strongly considered for antiopioid and/or antialcohol pharmacotherapy in addition to ART.

The study was supported by National Institutes of Health grants, and by Alkermes, which supplied XR-NTX and placebo to investigators. Dr. Springer disclosed research grants from the National Institute on Drug Abuse.

SOURCE: Springer S et al. CROI Abstract 96

Alterations in DNA damage response and repair genes may be useful biomarkers for response to immune checkpoint inhibitors in patients with urothelial carcinoma, investigators contend.

Among 60 patients with urothelial carcinoma in prospective trials of antibodies directed against the immune checkpoint inhibitor programmed cell death protein-1 and its ligand (PD-1/PD-L1), 28 (47%) had a damage response and repair (DDR) gene of any kind, and 15 (25%) had DDR mutations that are thought to be deleterious. Patients with any DDR mutations were more likely to have a clinical response to anti–PD-1/PD-L1 therapy, especially patients with likely deleterious mutations, reported Jonathan E. Rosenberg, MD and colleagues from Memorial Sloan Kettering Cancer Center, New York.

op@frontlinemedcom.com

SOURCE: Rosenberg JE et al. J Clin Oncol. 2018 Feb 28. doi: 10.1200/JCO.2017.75.7740.

Alterations in DNA damage response and repair genes may be useful biomarkers for response to immune checkpoint inhibitors in patients with urothelial carcinoma, investigators contend.

Among 60 patients with urothelial carcinoma in prospective trials of antibodies directed against the immune checkpoint inhibitor programmed cell death protein-1 and its ligand (PD-1/PD-L1), 28 (47%) had a damage response and repair (DDR) gene of any kind, and 15 (25%) had DDR mutations that are thought to be deleterious. Patients with any DDR mutations were more likely to have a clinical response to anti–PD-1/PD-L1 therapy, especially patients with likely deleterious mutations, reported Jonathan E. Rosenberg, MD and colleagues from Memorial Sloan Kettering Cancer Center, New York.

op@frontlinemedcom.com

SOURCE: Rosenberg JE et al. J Clin Oncol. 2018 Feb 28. doi: 10.1200/JCO.2017.75.7740.

Alterations in DNA damage response and repair genes may be useful biomarkers for response to immune checkpoint inhibitors in patients with urothelial carcinoma, investigators contend.

Among 60 patients with urothelial carcinoma in prospective trials of antibodies directed against the immune checkpoint inhibitor programmed cell death protein-1 and its ligand (PD-1/PD-L1), 28 (47%) had a damage response and repair (DDR) gene of any kind, and 15 (25%) had DDR mutations that are thought to be deleterious. Patients with any DDR mutations were more likely to have a clinical response to anti–PD-1/PD-L1 therapy, especially patients with likely deleterious mutations, reported Jonathan E. Rosenberg, MD and colleagues from Memorial Sloan Kettering Cancer Center, New York.

op@frontlinemedcom.com

SOURCE: Rosenberg JE et al. J Clin Oncol. 2018 Feb 28. doi: 10.1200/JCO.2017.75.7740.

High-deductible health insurance plans may be bad for women’s health, suggest results of a new study.

An analysis of data on women without evidence of breast cancer who were covered for at least 1 year in a low annual deductible plan and then switched by their employers to high annual deductible plans showed that when women were forced to shell out substantially more money before their insurance kicked in, they were significantly more likely to have delays in diagnostic breast imaging, breast biopsy, and initiation of chemotherapy.

“Such delays might lead to adverse long-term breast cancer outcomes. Policymakers, health insurers, and employers should consider designing or incentivizing health insurance benefits that facilitate transitions through key steps along the cancer care pathway,” wrote J. Frank Wharam, MB, and colleagues at Harvard Medical School and Harvard Pilgrim Health Care Institute in Boston. The report was published in Journal of Clinical Oncology.

op@frontlinemedcom.com

SOURCE: Wharam et al. J Clin Oncol. 2018 Feb 28. doi: 10.1200/JCO.2017.75.2501.

High-deductible health insurance plans may be bad for women’s health, suggest results of a new study.

An analysis of data on women without evidence of breast cancer who were covered for at least 1 year in a low annual deductible plan and then switched by their employers to high annual deductible plans showed that when women were forced to shell out substantially more money before their insurance kicked in, they were significantly more likely to have delays in diagnostic breast imaging, breast biopsy, and initiation of chemotherapy.

“Such delays might lead to adverse long-term breast cancer outcomes. Policymakers, health insurers, and employers should consider designing or incentivizing health insurance benefits that facilitate transitions through key steps along the cancer care pathway,” wrote J. Frank Wharam, MB, and colleagues at Harvard Medical School and Harvard Pilgrim Health Care Institute in Boston. The report was published in Journal of Clinical Oncology.

op@frontlinemedcom.com

SOURCE: Wharam et al. J Clin Oncol. 2018 Feb 28. doi: 10.1200/JCO.2017.75.2501.

High-deductible health insurance plans may be bad for women’s health, suggest results of a new study.

An analysis of data on women without evidence of breast cancer who were covered for at least 1 year in a low annual deductible plan and then switched by their employers to high annual deductible plans showed that when women were forced to shell out substantially more money before their insurance kicked in, they were significantly more likely to have delays in diagnostic breast imaging, breast biopsy, and initiation of chemotherapy.

“Such delays might lead to adverse long-term breast cancer outcomes. Policymakers, health insurers, and employers should consider designing or incentivizing health insurance benefits that facilitate transitions through key steps along the cancer care pathway,” wrote J. Frank Wharam, MB, and colleagues at Harvard Medical School and Harvard Pilgrim Health Care Institute in Boston. The report was published in Journal of Clinical Oncology.

op@frontlinemedcom.com

SOURCE: Wharam et al. J Clin Oncol. 2018 Feb 28. doi: 10.1200/JCO.2017.75.2501.

The tyrosine kinase inhibitor ibrutinib (Imbruvica) may be associated with early-onset invasive fungal infections (IFI) in patients with hematologic malignancies, investigators caution.

French investigators identified 33 cases of invasive fungal infections occurring among patients who had been treated with ibrutinib as monotherapy or in combination with other agents. Of the 33 cases, 27 were invasive aspergillosis, and 40% of these were localized in the central nervous system. The findings were published in the journal Blood.

“IFI tend to occur within the first months of treatment and are infrequent thereafter. Whilst it seems difficult at this point to advocate for systematic antifungal prophylaxis in all patients, an increased awareness about the potential risk of IFI after initiating ibrutinib is warranted, especially when other predisposing factors are associated,” wrote David Ghez, MD, PhD, and colleagues at the Gustave Roussy Institute in Villejuif and other centers in France.

Although ibrutinib, an inhibitor of Bruton’s tyrosine kinase, is generally considered to be less immunosuppressive than other therapies, it was associated with five cases of Pneumocystis jirovecii pneumonia in patients with chronic lymphocytic leukemia (CLL) treated with ibrutinib monotherapy in a 2016 report (Blood. 2016;128:1940-3). Of these five patients, four were treatment naive, suggesting that ibrutinib itself could increase risk for invasive opportunistic infections, Dr. Ghez and his colleagues noted.

hematologynews@frontlinemedcom.com

SOURCE: Ghez D et al., Blood. 2018 Feb 1. doi: 10.1182/blood-2017-11-818286.

The tyrosine kinase inhibitor ibrutinib (Imbruvica) may be associated with early-onset invasive fungal infections (IFI) in patients with hematologic malignancies, investigators caution.

French investigators identified 33 cases of invasive fungal infections occurring among patients who had been treated with ibrutinib as monotherapy or in combination with other agents. Of the 33 cases, 27 were invasive aspergillosis, and 40% of these were localized in the central nervous system. The findings were published in the journal Blood.

“IFI tend to occur within the first months of treatment and are infrequent thereafter. Whilst it seems difficult at this point to advocate for systematic antifungal prophylaxis in all patients, an increased awareness about the potential risk of IFI after initiating ibrutinib is warranted, especially when other predisposing factors are associated,” wrote David Ghez, MD, PhD, and colleagues at the Gustave Roussy Institute in Villejuif and other centers in France.

Although ibrutinib, an inhibitor of Bruton’s tyrosine kinase, is generally considered to be less immunosuppressive than other therapies, it was associated with five cases of Pneumocystis jirovecii pneumonia in patients with chronic lymphocytic leukemia (CLL) treated with ibrutinib monotherapy in a 2016 report (Blood. 2016;128:1940-3). Of these five patients, four were treatment naive, suggesting that ibrutinib itself could increase risk for invasive opportunistic infections, Dr. Ghez and his colleagues noted.

hematologynews@frontlinemedcom.com

SOURCE: Ghez D et al., Blood. 2018 Feb 1. doi: 10.1182/blood-2017-11-818286.

The tyrosine kinase inhibitor ibrutinib (Imbruvica) may be associated with early-onset invasive fungal infections (IFI) in patients with hematologic malignancies, investigators caution.

French investigators identified 33 cases of invasive fungal infections occurring among patients who had been treated with ibrutinib as monotherapy or in combination with other agents. Of the 33 cases, 27 were invasive aspergillosis, and 40% of these were localized in the central nervous system. The findings were published in the journal Blood.

“IFI tend to occur within the first months of treatment and are infrequent thereafter. Whilst it seems difficult at this point to advocate for systematic antifungal prophylaxis in all patients, an increased awareness about the potential risk of IFI after initiating ibrutinib is warranted, especially when other predisposing factors are associated,” wrote David Ghez, MD, PhD, and colleagues at the Gustave Roussy Institute in Villejuif and other centers in France.

Although ibrutinib, an inhibitor of Bruton’s tyrosine kinase, is generally considered to be less immunosuppressive than other therapies, it was associated with five cases of Pneumocystis jirovecii pneumonia in patients with chronic lymphocytic leukemia (CLL) treated with ibrutinib monotherapy in a 2016 report (Blood. 2016;128:1940-3). Of these five patients, four were treatment naive, suggesting that ibrutinib itself could increase risk for invasive opportunistic infections, Dr. Ghez and his colleagues noted.

hematologynews@frontlinemedcom.com

SOURCE: Ghez D et al., Blood. 2018 Feb 1. doi: 10.1182/blood-2017-11-818286.

BOSTON – Diagnosing HIV infections in the home and starting persons who tested positive on antiretroviral therapy on the same day significantly increased the likelihood that the HIV-positive individuals would show up at a clinic for care within 3 months of diagnosis. It also improved their odds for having viral suppression at 12 months, compared with those who tested positive but were referred to a clinic for starting ART therapy, the standard of care.

Among 278 residents of the southern African nation of Lesotho, 68.8% of those randomized to an intervention in which they were offered same-day, home-based ART initiation and were given a 30-day supply of medication had linked to care by 3 months of follow-up, compared with 43.1% of those who were diagnosed and then referred to a health care facility to be started on ART, reported Niklaus D. Labhardt, MD, from the Swiss Tropical and Public Health Institute in Basel, and his colleagues.

Neil Osterweil, Frontline Medical News

Results from the study were simultaneously published online in JAMA.

Although home-based testing for HIV by trained workers has become common in remote areas such as northern Lesotho, those who test positive may be lost to care and become reservoirs of infection in their communities.

In fact, only 33% of those who test positive at home take the necessary steps to receive care and start on lifelong viral suppression therapy, and “two out of three who tested positive actually remain without ART,” Dr, Labhardt said.

Compressing the testing-to-ART cascade into a single day as a means of getting more patients to start on ART has been accomplished successfully in the clinic, but never before in the home-based setting, he noted.

To see whether same-day ART initiation could be accomplished in the field, Dr. Labhardt and his colleagues designed a multicenter, randomized trial in 278 individuals aged 18 years and older from 268 households. The participants who tested HIV positive and were ART naive were chosen from among 6,655 households in rural villages and 17 urban areas in Lesotho who took part in a home-based testing program.

After giving consent, the participants were randomly assigned to either the same-day or standard of care groups.

In the same-day group, participants were offered home-based ART initiation, given a 1-month supply of drugs, and instructed to visit a specified health facility in 2-4 weeks for their first check-up and refill. The patients were scheduled for additional follow-up visits at 1.5, 3, 6, 9, and 12 months.

In the standard-of-care group, patients received posttest counseling at home and were given an appointment to their nearest health facility within the next 4 weeks; once they were linked to care, they were required to make at least two additional visits for testing prior to starting on ART. Once they started ART, they were given monthly follow-up and drug-refill appointments.

The absolute difference in 3-month linkage rates between the same-day and standard-of-care groups was 25.6% (P = .001), and the difference in 12-month viral suppression rates was 16% (P less than .007).

Retention of care, looking only at those patients who continued visits at their assigned clinics, also was significantly better among patients in the same-day group throughout the study (P = .009).

The investigators acknowledged that the study was limited by being restricted to a rural setting with a very high prevalence of HIV and that they did not have information about the possible development of drug-resistant virus among patients who started on same-day therapy but did not complete the health care link. In addition, there was only limited information available about those patients who neither linked to care or dropped out.

Dr. Labhardt said at the briefing that the same-day intervention could likely be successfully implemented in similar settings in other parts rural Africa with high HIV prevalence.

SOURCE: Labhardt ND et al. JAMA. 2018 Mar 1. doi: 10.1001/jama.2018.1818.

BOSTON – Diagnosing HIV infections in the home and starting persons who tested positive on antiretroviral therapy on the same day significantly increased the likelihood that the HIV-positive individuals would show up at a clinic for care within 3 months of diagnosis. It also improved their odds for having viral suppression at 12 months, compared with those who tested positive but were referred to a clinic for starting ART therapy, the standard of care.

Among 278 residents of the southern African nation of Lesotho, 68.8% of those randomized to an intervention in which they were offered same-day, home-based ART initiation and were given a 30-day supply of medication had linked to care by 3 months of follow-up, compared with 43.1% of those who were diagnosed and then referred to a health care facility to be started on ART, reported Niklaus D. Labhardt, MD, from the Swiss Tropical and Public Health Institute in Basel, and his colleagues.

Neil Osterweil, Frontline Medical News

Results from the study were simultaneously published online in JAMA.

Although home-based testing for HIV by trained workers has become common in remote areas such as northern Lesotho, those who test positive may be lost to care and become reservoirs of infection in their communities.

In fact, only 33% of those who test positive at home take the necessary steps to receive care and start on lifelong viral suppression therapy, and “two out of three who tested positive actually remain without ART,” Dr, Labhardt said.

Compressing the testing-to-ART cascade into a single day as a means of getting more patients to start on ART has been accomplished successfully in the clinic, but never before in the home-based setting, he noted.

To see whether same-day ART initiation could be accomplished in the field, Dr. Labhardt and his colleagues designed a multicenter, randomized trial in 278 individuals aged 18 years and older from 268 households. The participants who tested HIV positive and were ART naive were chosen from among 6,655 households in rural villages and 17 urban areas in Lesotho who took part in a home-based testing program.

After giving consent, the participants were randomly assigned to either the same-day or standard of care groups.

In the same-day group, participants were offered home-based ART initiation, given a 1-month supply of drugs, and instructed to visit a specified health facility in 2-4 weeks for their first check-up and refill. The patients were scheduled for additional follow-up visits at 1.5, 3, 6, 9, and 12 months.

In the standard-of-care group, patients received posttest counseling at home and were given an appointment to their nearest health facility within the next 4 weeks; once they were linked to care, they were required to make at least two additional visits for testing prior to starting on ART. Once they started ART, they were given monthly follow-up and drug-refill appointments.

The absolute difference in 3-month linkage rates between the same-day and standard-of-care groups was 25.6% (P = .001), and the difference in 12-month viral suppression rates was 16% (P less than .007).

Retention of care, looking only at those patients who continued visits at their assigned clinics, also was significantly better among patients in the same-day group throughout the study (P = .009).

The investigators acknowledged that the study was limited by being restricted to a rural setting with a very high prevalence of HIV and that they did not have information about the possible development of drug-resistant virus among patients who started on same-day therapy but did not complete the health care link. In addition, there was only limited information available about those patients who neither linked to care or dropped out.

Dr. Labhardt said at the briefing that the same-day intervention could likely be successfully implemented in similar settings in other parts rural Africa with high HIV prevalence.

SOURCE: Labhardt ND et al. JAMA. 2018 Mar 1. doi: 10.1001/jama.2018.1818.

BOSTON – Diagnosing HIV infections in the home and starting persons who tested positive on antiretroviral therapy on the same day significantly increased the likelihood that the HIV-positive individuals would show up at a clinic for care within 3 months of diagnosis. It also improved their odds for having viral suppression at 12 months, compared with those who tested positive but were referred to a clinic for starting ART therapy, the standard of care.

Among 278 residents of the southern African nation of Lesotho, 68.8% of those randomized to an intervention in which they were offered same-day, home-based ART initiation and were given a 30-day supply of medication had linked to care by 3 months of follow-up, compared with 43.1% of those who were diagnosed and then referred to a health care facility to be started on ART, reported Niklaus D. Labhardt, MD, from the Swiss Tropical and Public Health Institute in Basel, and his colleagues.

Neil Osterweil, Frontline Medical News

Results from the study were simultaneously published online in JAMA.

Although home-based testing for HIV by trained workers has become common in remote areas such as northern Lesotho, those who test positive may be lost to care and become reservoirs of infection in their communities.

In fact, only 33% of those who test positive at home take the necessary steps to receive care and start on lifelong viral suppression therapy, and “two out of three who tested positive actually remain without ART,” Dr, Labhardt said.

Compressing the testing-to-ART cascade into a single day as a means of getting more patients to start on ART has been accomplished successfully in the clinic, but never before in the home-based setting, he noted.

To see whether same-day ART initiation could be accomplished in the field, Dr. Labhardt and his colleagues designed a multicenter, randomized trial in 278 individuals aged 18 years and older from 268 households. The participants who tested HIV positive and were ART naive were chosen from among 6,655 households in rural villages and 17 urban areas in Lesotho who took part in a home-based testing program.

After giving consent, the participants were randomly assigned to either the same-day or standard of care groups.

In the same-day group, participants were offered home-based ART initiation, given a 1-month supply of drugs, and instructed to visit a specified health facility in 2-4 weeks for their first check-up and refill. The patients were scheduled for additional follow-up visits at 1.5, 3, 6, 9, and 12 months.

In the standard-of-care group, patients received posttest counseling at home and were given an appointment to their nearest health facility within the next 4 weeks; once they were linked to care, they were required to make at least two additional visits for testing prior to starting on ART. Once they started ART, they were given monthly follow-up and drug-refill appointments.

The absolute difference in 3-month linkage rates between the same-day and standard-of-care groups was 25.6% (P = .001), and the difference in 12-month viral suppression rates was 16% (P less than .007).

Retention of care, looking only at those patients who continued visits at their assigned clinics, also was significantly better among patients in the same-day group throughout the study (P = .009).

The investigators acknowledged that the study was limited by being restricted to a rural setting with a very high prevalence of HIV and that they did not have information about the possible development of drug-resistant virus among patients who started on same-day therapy but did not complete the health care link. In addition, there was only limited information available about those patients who neither linked to care or dropped out.

Dr. Labhardt said at the briefing that the same-day intervention could likely be successfully implemented in similar settings in other parts rural Africa with high HIV prevalence.

SOURCE: Labhardt ND et al. JAMA. 2018 Mar 1. doi: 10.1001/jama.2018.1818.

BOSTON – A combination regimen of rifapentine­ plus isoniazid (1HP) can do in 1 month what it takes isoniazid monotherapy 9 months to accomplish: effectively prevent tuberculosis in persons with HIV infection, investigators in the randomized phase 3 BRIEF TB trial reported.

“Rates of tuberculosis or death in individuals on 1HP were essentially identical to the rates of tuberculosis or death in people who got the 9-months regimen,” said Richard Chaisson, MD, of Johns Hopkins University, Baltimore.

“People who got the 1-month regimen were more likely to complete it, had slightly less toxicity, and overall had very similar clinical outcomes,” he said at the annual Conference on Retroviruses & Opportunistic Infections.

Worldwide, more than 1,000 persons with HIV infection die from tuberculosis every day, he noted.

Although isoniazid preventive therapy (IPT) is highly effective, the rate of its use has been “appallingly poor,” Dr. Chaisson said.

“There’s a sense of futility amongst clinicians around the world, that they’re not going to even bother with giving TB-preventive therapy,” he commented.

Neil Osterweil/Frontline Medical News

Dr. Chaisson and coinvestigators conducted a randomized trial to test the hypothesis that 4 weeks of daily rifapentine and isoniazid would be noninferior to 9 months of isoniazid for TB prevention in person with HIV infection.

In a multicenter open-label trial, they enrolled 3,000 HIV-infected people aged 13 years and older from 45 sites in 10 countries. The patients had no evidence of active TB, but had either tuberculin skin test (TST) reactivity of 5 mm or greater and/or a positive interferon gamma release assay (IGRA), or lived in a high–TB burden area (prevalence of 60 or more cases per 100,000 population).

Patients were stratified by CD4+ cell count and antiretroviral therapy use at base line (yes or no). The median CD4 count was 470 cells/mm³, and 50% of patients were on ART. Only efavirenz-based or nevirapine-based ART was allowed during IPT therapy.

In the experimental arm, patients were randomized to 4 weeks of rifapentine 450 mg for those less than 45 kg, or 600 mg for those 45 kg or higher, plus 300 mg isoniazid daily, plus 25 mg vitamin B6, followed by 32 weeks of observation.

Patients in the control arm received isoniazid and vitamin B₆ daily for 36 weeks.

 A total of 1,498 patients assigned to standard-of-care isoniazid and 1,488 assigned to 1HP were available for the efficacy analysis.

Three years after the last patient had been enrolled, the primary endpoint – the incidence rate of first diagnosis of active TB, TB death, or death from an unknown cause – had occurred in 32 patients on the 1HP regimen, and 33 on 9-month isoniazid.

Events included confirmed active TB in 18 patients on 1HP and 14 on isoniazid, probable active TB in 11 and 10 patients, respectively, death related to TB in 2 patients on 9-month isoniazid (none in the 1HP group) and death from unknown causes in 3 and 7 patients, respectively.

The incidence of events per 100 person-years of follow-up was 0.65 for the 1HP regimen and 0.67 for 9 months of isoniazid, a difference that was not statistically significant.

There were two cases of isoniazid resistance and one of rifampin resistance in the 1HP arm vs. one each in the 9-month isoniazid arm. There were no cases of multidrug resistance in either arm.

The safety analysis showed that 83 patients on 1HP had at least one serious adverse event, compared with 108 patients on the 9-month regimen.

“This 1 HP regimen really could dramatically alter the landscape for preventing TB in people with HIV. It’s a simple regimen; it can be given to people with HIV, and the likelihood of them completing it is extremely high; and the likelihood of it working is extremely good,” Dr. Chaisson said at media briefing following his presentation of the data in session.

The study was funded by National Institute of Health grants. Sanofi supplied study medications. Dr. Chaisson disclosed serving as a consultant to Otsuka, and that his spouse is a Merck shareholder.

BOSTON – A combination regimen of rifapentine­ plus isoniazid (1HP) can do in 1 month what it takes isoniazid monotherapy 9 months to accomplish: effectively prevent tuberculosis in persons with HIV infection, investigators in the randomized phase 3 BRIEF TB trial reported.

“Rates of tuberculosis or death in individuals on 1HP were essentially identical to the rates of tuberculosis or death in people who got the 9-months regimen,” said Richard Chaisson, MD, of Johns Hopkins University, Baltimore.

“People who got the 1-month regimen were more likely to complete it, had slightly less toxicity, and overall had very similar clinical outcomes,” he said at the annual Conference on Retroviruses & Opportunistic Infections.

Worldwide, more than 1,000 persons with HIV infection die from tuberculosis every day, he noted.

Although isoniazid preventive therapy (IPT) is highly effective, the rate of its use has been “appallingly poor,” Dr. Chaisson said.

“There’s a sense of futility amongst clinicians around the world, that they’re not going to even bother with giving TB-preventive therapy,” he commented.

Neil Osterweil/Frontline Medical News

Dr. Chaisson and coinvestigators conducted a randomized trial to test the hypothesis that 4 weeks of daily rifapentine and isoniazid would be noninferior to 9 months of isoniazid for TB prevention in person with HIV infection.

In a multicenter open-label trial, they enrolled 3,000 HIV-infected people aged 13 years and older from 45 sites in 10 countries. The patients had no evidence of active TB, but had either tuberculin skin test (TST) reactivity of 5 mm or greater and/or a positive interferon gamma release assay (IGRA), or lived in a high–TB burden area (prevalence of 60 or more cases per 100,000 population).

Patients were stratified by CD4+ cell count and antiretroviral therapy use at base line (yes or no). The median CD4 count was 470 cells/mm³, and 50% of patients were on ART. Only efavirenz-based or nevirapine-based ART was allowed during IPT therapy.

In the experimental arm, patients were randomized to 4 weeks of rifapentine 450 mg for those less than 45 kg, or 600 mg for those 45 kg or higher, plus 300 mg isoniazid daily, plus 25 mg vitamin B6, followed by 32 weeks of observation.

Patients in the control arm received isoniazid and vitamin B₆ daily for 36 weeks.

 A total of 1,498 patients assigned to standard-of-care isoniazid and 1,488 assigned to 1HP were available for the efficacy analysis.

Three years after the last patient had been enrolled, the primary endpoint – the incidence rate of first diagnosis of active TB, TB death, or death from an unknown cause – had occurred in 32 patients on the 1HP regimen, and 33 on 9-month isoniazid.

Events included confirmed active TB in 18 patients on 1HP and 14 on isoniazid, probable active TB in 11 and 10 patients, respectively, death related to TB in 2 patients on 9-month isoniazid (none in the 1HP group) and death from unknown causes in 3 and 7 patients, respectively.

The incidence of events per 100 person-years of follow-up was 0.65 for the 1HP regimen and 0.67 for 9 months of isoniazid, a difference that was not statistically significant.

There were two cases of isoniazid resistance and one of rifampin resistance in the 1HP arm vs. one each in the 9-month isoniazid arm. There were no cases of multidrug resistance in either arm.

The safety analysis showed that 83 patients on 1HP had at least one serious adverse event, compared with 108 patients on the 9-month regimen.

“This 1 HP regimen really could dramatically alter the landscape for preventing TB in people with HIV. It’s a simple regimen; it can be given to people with HIV, and the likelihood of them completing it is extremely high; and the likelihood of it working is extremely good,” Dr. Chaisson said at media briefing following his presentation of the data in session.

The study was funded by National Institute of Health grants. Sanofi supplied study medications. Dr. Chaisson disclosed serving as a consultant to Otsuka, and that his spouse is a Merck shareholder.

BOSTON – A combination regimen of rifapentine­ plus isoniazid (1HP) can do in 1 month what it takes isoniazid monotherapy 9 months to accomplish: effectively prevent tuberculosis in persons with HIV infection, investigators in the randomized phase 3 BRIEF TB trial reported.

“Rates of tuberculosis or death in individuals on 1HP were essentially identical to the rates of tuberculosis or death in people who got the 9-months regimen,” said Richard Chaisson, MD, of Johns Hopkins University, Baltimore.

“People who got the 1-month regimen were more likely to complete it, had slightly less toxicity, and overall had very similar clinical outcomes,” he said at the annual Conference on Retroviruses & Opportunistic Infections.

Worldwide, more than 1,000 persons with HIV infection die from tuberculosis every day, he noted.

Although isoniazid preventive therapy (IPT) is highly effective, the rate of its use has been “appallingly poor,” Dr. Chaisson said.

“There’s a sense of futility amongst clinicians around the world, that they’re not going to even bother with giving TB-preventive therapy,” he commented.

Neil Osterweil/Frontline Medical News

Dr. Chaisson and coinvestigators conducted a randomized trial to test the hypothesis that 4 weeks of daily rifapentine and isoniazid would be noninferior to 9 months of isoniazid for TB prevention in person with HIV infection.

In a multicenter open-label trial, they enrolled 3,000 HIV-infected people aged 13 years and older from 45 sites in 10 countries. The patients had no evidence of active TB, but had either tuberculin skin test (TST) reactivity of 5 mm or greater and/or a positive interferon gamma release assay (IGRA), or lived in a high–TB burden area (prevalence of 60 or more cases per 100,000 population).

Patients were stratified by CD4+ cell count and antiretroviral therapy use at base line (yes or no). The median CD4 count was 470 cells/mm³, and 50% of patients were on ART. Only efavirenz-based or nevirapine-based ART was allowed during IPT therapy.

In the experimental arm, patients were randomized to 4 weeks of rifapentine 450 mg for those less than 45 kg, or 600 mg for those 45 kg or higher, plus 300 mg isoniazid daily, plus 25 mg vitamin B6, followed by 32 weeks of observation.

Patients in the control arm received isoniazid and vitamin B₆ daily for 36 weeks.

 A total of 1,498 patients assigned to standard-of-care isoniazid and 1,488 assigned to 1HP were available for the efficacy analysis.

Three years after the last patient had been enrolled, the primary endpoint – the incidence rate of first diagnosis of active TB, TB death, or death from an unknown cause – had occurred in 32 patients on the 1HP regimen, and 33 on 9-month isoniazid.

Events included confirmed active TB in 18 patients on 1HP and 14 on isoniazid, probable active TB in 11 and 10 patients, respectively, death related to TB in 2 patients on 9-month isoniazid (none in the 1HP group) and death from unknown causes in 3 and 7 patients, respectively.

The incidence of events per 100 person-years of follow-up was 0.65 for the 1HP regimen and 0.67 for 9 months of isoniazid, a difference that was not statistically significant.

There were two cases of isoniazid resistance and one of rifampin resistance in the 1HP arm vs. one each in the 9-month isoniazid arm. There were no cases of multidrug resistance in either arm.

The safety analysis showed that 83 patients on 1HP had at least one serious adverse event, compared with 108 patients on the 9-month regimen.

“This 1 HP regimen really could dramatically alter the landscape for preventing TB in people with HIV. It’s a simple regimen; it can be given to people with HIV, and the likelihood of them completing it is extremely high; and the likelihood of it working is extremely good,” Dr. Chaisson said at media briefing following his presentation of the data in session.

The study was funded by National Institute of Health grants. Sanofi supplied study medications. Dr. Chaisson disclosed serving as a consultant to Otsuka, and that his spouse is a Merck shareholder.

The immune checkpoint inhibitor avelumab (Bavencio), targeted against programmed cell death protein 1 and its ligand (PD1/PD-L1), appears to be well tolerated with a manageable safety profile, pooled data from two clinical trials suggest.

Of the 1,738 patients enrolled in the phase 1 JAVELIN solid tumor trial and the phase 2 JAVELIN Merkel 200 trial, 1,164 (67%) had a treatment-related adverse event (TRAE), and 177 (10.2%) had grade 3 or greater TRAEs. Grade 3 or greater immune-related adverse events (irAEs) occurred in just 2.2% of patients, reported Karen Kelly, MD, from the University of California, Davis, and her colleagues.

“Although conclusions drawn from cross-study comparisons should be made with caution, and to the best of our knowledge the number of pan-tumor clinical studies of [immune checkpoint inhibitor] monotherapy is limited, this analysis of a large population of patients across a broad scope of tumor types suggests that avelumab was associated with an incidence of irAEs that is consistent with that of other ICIs,” they wrote in Cancer.

Adverse events common with other immune checkpoint inhibitors include low-grade fatigue, pruritus, and rash, as well as serious irAEs, including high-grade pneumonitis and autoimmune-like side effects, the authors noted.

To characterize the adverse event profile of avelumab, they reviewed safety data on 1,650 patients enrolled in the solid tumor trial and 88 enrolled in the Merkel cell carcinoma trial, which included all patients in the trial who had received at least one dose of avelumab monotherapy by the cutoff date.

At the time of the analysis, 287 patients (16.5%) were continuing treatment, and 1,451 had discontinued therapy, largely because of disease progression.

Nearly all patients – 1,697 (97.6%) – had at least one adverse event of any grade or cause.

Four patients died from what investigators determined were TRAEs, including autoimmune hepatitis with peritoneal metastases and ascites in a patient with gastric cancer, liver metastases and acute liver failure in a patient with metastatic breast cancer, respiratory distress in a patient with breast cancer and multiple comorbidities, and treatment-related pneumonitis with ongoing Clostridium difficile colitis and diverticulitis not related to study treatment in a patient with urothelial carcinoma.

An additional 59 patients (3.4%) died from adverse events not deemed to be treatment-related, and 104 patient (6%) died from unknown or undocumented causes.

Any grade of irAE occurred in 247 patients (14.2%) and were grade 3 or greater in 39 (2.2%). Management of irAEs included systemic corticosteroids and nonsteroidal immunosuppressants.

In all, 439 patients (25.3%) had infusion-related reactions, which were treated generally with systemic corticosteroid. The protocol of the solid tumor trial was amended later to include diphenhydramine and acetaminophen before the first avelumab infusion as prophylaxis.

The study was sponsored by Merck and part of an alliance between Merck and Pfizer. Dr. Kelly reported no conflicts of interest. Multiple coauthors reported research funding, consulting fees, honoraria, or other consideration from various companies, and several coauthors are Merck employees.

The immune checkpoint inhibitor avelumab (Bavencio), targeted against programmed cell death protein 1 and its ligand (PD1/PD-L1), appears to be well tolerated with a manageable safety profile, pooled data from two clinical trials suggest.

Of the 1,738 patients enrolled in the phase 1 JAVELIN solid tumor trial and the phase 2 JAVELIN Merkel 200 trial, 1,164 (67%) had a treatment-related adverse event (TRAE), and 177 (10.2%) had grade 3 or greater TRAEs. Grade 3 or greater immune-related adverse events (irAEs) occurred in just 2.2% of patients, reported Karen Kelly, MD, from the University of California, Davis, and her colleagues.

“Although conclusions drawn from cross-study comparisons should be made with caution, and to the best of our knowledge the number of pan-tumor clinical studies of [immune checkpoint inhibitor] monotherapy is limited, this analysis of a large population of patients across a broad scope of tumor types suggests that avelumab was associated with an incidence of irAEs that is consistent with that of other ICIs,” they wrote in Cancer.

Adverse events common with other immune checkpoint inhibitors include low-grade fatigue, pruritus, and rash, as well as serious irAEs, including high-grade pneumonitis and autoimmune-like side effects, the authors noted.

To characterize the adverse event profile of avelumab, they reviewed safety data on 1,650 patients enrolled in the solid tumor trial and 88 enrolled in the Merkel cell carcinoma trial, which included all patients in the trial who had received at least one dose of avelumab monotherapy by the cutoff date.

At the time of the analysis, 287 patients (16.5%) were continuing treatment, and 1,451 had discontinued therapy, largely because of disease progression.

Nearly all patients – 1,697 (97.6%) – had at least one adverse event of any grade or cause.

Four patients died from what investigators determined were TRAEs, including autoimmune hepatitis with peritoneal metastases and ascites in a patient with gastric cancer, liver metastases and acute liver failure in a patient with metastatic breast cancer, respiratory distress in a patient with breast cancer and multiple comorbidities, and treatment-related pneumonitis with ongoing Clostridium difficile colitis and diverticulitis not related to study treatment in a patient with urothelial carcinoma.

An additional 59 patients (3.4%) died from adverse events not deemed to be treatment-related, and 104 patient (6%) died from unknown or undocumented causes.

Any grade of irAE occurred in 247 patients (14.2%) and were grade 3 or greater in 39 (2.2%). Management of irAEs included systemic corticosteroids and nonsteroidal immunosuppressants.

In all, 439 patients (25.3%) had infusion-related reactions, which were treated generally with systemic corticosteroid. The protocol of the solid tumor trial was amended later to include diphenhydramine and acetaminophen before the first avelumab infusion as prophylaxis.

The study was sponsored by Merck and part of an alliance between Merck and Pfizer. Dr. Kelly reported no conflicts of interest. Multiple coauthors reported research funding, consulting fees, honoraria, or other consideration from various companies, and several coauthors are Merck employees.

The immune checkpoint inhibitor avelumab (Bavencio), targeted against programmed cell death protein 1 and its ligand (PD1/PD-L1), appears to be well tolerated with a manageable safety profile, pooled data from two clinical trials suggest.

Of the 1,738 patients enrolled in the phase 1 JAVELIN solid tumor trial and the phase 2 JAVELIN Merkel 200 trial, 1,164 (67%) had a treatment-related adverse event (TRAE), and 177 (10.2%) had grade 3 or greater TRAEs. Grade 3 or greater immune-related adverse events (irAEs) occurred in just 2.2% of patients, reported Karen Kelly, MD, from the University of California, Davis, and her colleagues.

“Although conclusions drawn from cross-study comparisons should be made with caution, and to the best of our knowledge the number of pan-tumor clinical studies of [immune checkpoint inhibitor] monotherapy is limited, this analysis of a large population of patients across a broad scope of tumor types suggests that avelumab was associated with an incidence of irAEs that is consistent with that of other ICIs,” they wrote in Cancer.

Adverse events common with other immune checkpoint inhibitors include low-grade fatigue, pruritus, and rash, as well as serious irAEs, including high-grade pneumonitis and autoimmune-like side effects, the authors noted.

To characterize the adverse event profile of avelumab, they reviewed safety data on 1,650 patients enrolled in the solid tumor trial and 88 enrolled in the Merkel cell carcinoma trial, which included all patients in the trial who had received at least one dose of avelumab monotherapy by the cutoff date.

At the time of the analysis, 287 patients (16.5%) were continuing treatment, and 1,451 had discontinued therapy, largely because of disease progression.

Nearly all patients – 1,697 (97.6%) – had at least one adverse event of any grade or cause.

Four patients died from what investigators determined were TRAEs, including autoimmune hepatitis with peritoneal metastases and ascites in a patient with gastric cancer, liver metastases and acute liver failure in a patient with metastatic breast cancer, respiratory distress in a patient with breast cancer and multiple comorbidities, and treatment-related pneumonitis with ongoing Clostridium difficile colitis and diverticulitis not related to study treatment in a patient with urothelial carcinoma.

An additional 59 patients (3.4%) died from adverse events not deemed to be treatment-related, and 104 patient (6%) died from unknown or undocumented causes.

Any grade of irAE occurred in 247 patients (14.2%) and were grade 3 or greater in 39 (2.2%). Management of irAEs included systemic corticosteroids and nonsteroidal immunosuppressants.

In all, 439 patients (25.3%) had infusion-related reactions, which were treated generally with systemic corticosteroid. The protocol of the solid tumor trial was amended later to include diphenhydramine and acetaminophen before the first avelumab infusion as prophylaxis.

The study was sponsored by Merck and part of an alliance between Merck and Pfizer. Dr. Kelly reported no conflicts of interest. Multiple coauthors reported research funding, consulting fees, honoraria, or other consideration from various companies, and several coauthors are Merck employees.

More fuel for the radiation vs. surgery in prostate cancer debate comes from a study suggesting that patients with high-risk localized prostate cancer treated with external beam radiotherapy (EBRT) plus brachytherapy – with or without androgen deprivation (AD) – have survival rates equivalent to those of patients treated with radical prostatectomy (RP).

However, patients treated with EBRT and androgen deprivation without brachytherapy had significantly worse survival compared with patients treated with surgery, according to Ronald D. Ennis, MD, of Rutgers Cancer Institute of New Jersey, New Brunswick, and his colleagues.

“The data reported herein suggest that RT plus brachytherapy with or without AD and RP are associated with similar survival. This finding reinforces the need for patients to seek opinions from both a urologic oncologic surgeon with expertise in RP and a radiation oncologist with expertise in brachytherapy. The natural human tendency for physicians to prefer their modality necessitates this dual consultation approach, preferably in a single joint consultation visit,” the researchers wrote. The report was published in the Journal of Clinical Oncology.

The investigators attempted to control for variables that could influence the results by drawing on data on a large number of patients – 42,765 – who were treated at a large number of facilities across the United States. In addition, they incorporated data on clinical stage and Gleason score for all patients, prostate-specific antigen measurements, comorbidities, and socioeconomic factors that are either known or thought to influence treatment decisions.

They used inverse probability of treatment weight to adjust for imbalances of covariables among the treatment groups, and then created weighted time-dependent Cox proportional hazard models to estimate the effects of each type of treatment on survival.

Their sample included 24,688 patients who underwent RP, 15,435 who received EBRT with AD, and 2,642 who underwent EBRT and brachytherapy with or without AD.

­They found no statistical difference in survival between RP and EBRT plus brachytherapy with/without AD in inverse probability of treatment weighted analysis. The hazard ratio for EBRT/brachytherapy was 1.17, but this was not statistically significant (95% confidence interval, 0.88-1.55).

In contrast. EBRT plus AD was associated with significantly worse survival, with a hazard ration of 1.53 (95% CI, 1.22-1.92).

The authors noted that “this finding reinforces the importance of complications, particularly in the urinary, sexual, and bowel domains, in combination with patient priorities and preferences, in determining an individual patient’s optimal choice. Significant data have been published in recent years regarding patient-reported outcomes that should be shared with all new patients to help guide them to their personal optimal treatment.”

They added that for some patients, quality of life may be a more important factor than survival when choosing a treatment modality.

SOURCE: Ennis et al. J Clin Oncol. 2018 Feb 28. doi: 10.1200/JCO.2017.75.9134

More fuel for the radiation vs. surgery in prostate cancer debate comes from a study suggesting that patients with high-risk localized prostate cancer treated with external beam radiotherapy (EBRT) plus brachytherapy – with or without androgen deprivation (AD) – have survival rates equivalent to those of patients treated with radical prostatectomy (RP).

However, patients treated with EBRT and androgen deprivation without brachytherapy had significantly worse survival compared with patients treated with surgery, according to Ronald D. Ennis, MD, of Rutgers Cancer Institute of New Jersey, New Brunswick, and his colleagues.

“The data reported herein suggest that RT plus brachytherapy with or without AD and RP are associated with similar survival. This finding reinforces the need for patients to seek opinions from both a urologic oncologic surgeon with expertise in RP and a radiation oncologist with expertise in brachytherapy. The natural human tendency for physicians to prefer their modality necessitates this dual consultation approach, preferably in a single joint consultation visit,” the researchers wrote. The report was published in the Journal of Clinical Oncology.

The investigators attempted to control for variables that could influence the results by drawing on data on a large number of patients – 42,765 – who were treated at a large number of facilities across the United States. In addition, they incorporated data on clinical stage and Gleason score for all patients, prostate-specific antigen measurements, comorbidities, and socioeconomic factors that are either known or thought to influence treatment decisions.

They used inverse probability of treatment weight to adjust for imbalances of covariables among the treatment groups, and then created weighted time-dependent Cox proportional hazard models to estimate the effects of each type of treatment on survival.

Their sample included 24,688 patients who underwent RP, 15,435 who received EBRT with AD, and 2,642 who underwent EBRT and brachytherapy with or without AD.

­They found no statistical difference in survival between RP and EBRT plus brachytherapy with/without AD in inverse probability of treatment weighted analysis. The hazard ratio for EBRT/brachytherapy was 1.17, but this was not statistically significant (95% confidence interval, 0.88-1.55).

In contrast. EBRT plus AD was associated with significantly worse survival, with a hazard ration of 1.53 (95% CI, 1.22-1.92).

The authors noted that “this finding reinforces the importance of complications, particularly in the urinary, sexual, and bowel domains, in combination with patient priorities and preferences, in determining an individual patient’s optimal choice. Significant data have been published in recent years regarding patient-reported outcomes that should be shared with all new patients to help guide them to their personal optimal treatment.”

They added that for some patients, quality of life may be a more important factor than survival when choosing a treatment modality.

SOURCE: Ennis et al. J Clin Oncol. 2018 Feb 28. doi: 10.1200/JCO.2017.75.9134

More fuel for the radiation vs. surgery in prostate cancer debate comes from a study suggesting that patients with high-risk localized prostate cancer treated with external beam radiotherapy (EBRT) plus brachytherapy – with or without androgen deprivation (AD) – have survival rates equivalent to those of patients treated with radical prostatectomy (RP).

However, patients treated with EBRT and androgen deprivation without brachytherapy had significantly worse survival compared with patients treated with surgery, according to Ronald D. Ennis, MD, of Rutgers Cancer Institute of New Jersey, New Brunswick, and his colleagues.

“The data reported herein suggest that RT plus brachytherapy with or without AD and RP are associated with similar survival. This finding reinforces the need for patients to seek opinions from both a urologic oncologic surgeon with expertise in RP and a radiation oncologist with expertise in brachytherapy. The natural human tendency for physicians to prefer their modality necessitates this dual consultation approach, preferably in a single joint consultation visit,” the researchers wrote. The report was published in the Journal of Clinical Oncology.

The investigators attempted to control for variables that could influence the results by drawing on data on a large number of patients – 42,765 – who were treated at a large number of facilities across the United States. In addition, they incorporated data on clinical stage and Gleason score for all patients, prostate-specific antigen measurements, comorbidities, and socioeconomic factors that are either known or thought to influence treatment decisions.

They used inverse probability of treatment weight to adjust for imbalances of covariables among the treatment groups, and then created weighted time-dependent Cox proportional hazard models to estimate the effects of each type of treatment on survival.

Their sample included 24,688 patients who underwent RP, 15,435 who received EBRT with AD, and 2,642 who underwent EBRT and brachytherapy with or without AD.

­They found no statistical difference in survival between RP and EBRT plus brachytherapy with/without AD in inverse probability of treatment weighted analysis. The hazard ratio for EBRT/brachytherapy was 1.17, but this was not statistically significant (95% confidence interval, 0.88-1.55).

In contrast. EBRT plus AD was associated with significantly worse survival, with a hazard ration of 1.53 (95% CI, 1.22-1.92).

The authors noted that “this finding reinforces the importance of complications, particularly in the urinary, sexual, and bowel domains, in combination with patient priorities and preferences, in determining an individual patient’s optimal choice. Significant data have been published in recent years regarding patient-reported outcomes that should be shared with all new patients to help guide them to their personal optimal treatment.”

They added that for some patients, quality of life may be a more important factor than survival when choosing a treatment modality.

SOURCE: Ennis et al. J Clin Oncol. 2018 Feb 28. doi: 10.1200/JCO.2017.75.9134