Neil Osterweil

ATLANTA – In the ZUMA-1 trial, more than one-third of patients with refractory large B-cell lymphomas treated with the chimeric antigen receptor (CAR) T-cell product axicabtagene ciloleucel (Yescarta; axi-cel) had durable responses, with some patients having complete responses lasting more than 1 year after a single infusion.

Updated combined phase 1 and 2 results in 108 patients with diffuse large B-cell lymphoma, primary mediastinal B-cell lymphoma, or transformed follicular lymphoma showed an objective response rate of 82% of patients – including 58% showing complete responses – after a median follow-up of 15.4 months.

In a video interview at the annual meeting of the American Society of Hematology, Sattva S. Neelapu, MD, from the University of Texas MD Anderson Cancer Center in Houston discusses the use of CAR T cells directed against the CD19 antigen in patients with relapsed/refractory B-cell lymphomas and describes efforts to improve responses while managing adverse events common to CAR T-cell therapies, notably cytokine release syndrome.

ZUMA-1 is supported by Kite Pharma, which developed axicabtagene ciloleucel, and the Leukemia & Lymphoma Society’s Therapy Acceleration Program. Dr. Neelapu reported receiving advisory board fees from the company.

ATLANTA – In the ZUMA-1 trial, more than one-third of patients with refractory large B-cell lymphomas treated with the chimeric antigen receptor (CAR) T-cell product axicabtagene ciloleucel (Yescarta; axi-cel) had durable responses, with some patients having complete responses lasting more than 1 year after a single infusion.

Updated combined phase 1 and 2 results in 108 patients with diffuse large B-cell lymphoma, primary mediastinal B-cell lymphoma, or transformed follicular lymphoma showed an objective response rate of 82% of patients – including 58% showing complete responses – after a median follow-up of 15.4 months.

In a video interview at the annual meeting of the American Society of Hematology, Sattva S. Neelapu, MD, from the University of Texas MD Anderson Cancer Center in Houston discusses the use of CAR T cells directed against the CD19 antigen in patients with relapsed/refractory B-cell lymphomas and describes efforts to improve responses while managing adverse events common to CAR T-cell therapies, notably cytokine release syndrome.

ZUMA-1 is supported by Kite Pharma, which developed axicabtagene ciloleucel, and the Leukemia & Lymphoma Society’s Therapy Acceleration Program. Dr. Neelapu reported receiving advisory board fees from the company.

ATLANTA – In the ZUMA-1 trial, more than one-third of patients with refractory large B-cell lymphomas treated with the chimeric antigen receptor (CAR) T-cell product axicabtagene ciloleucel (Yescarta; axi-cel) had durable responses, with some patients having complete responses lasting more than 1 year after a single infusion.

Updated combined phase 1 and 2 results in 108 patients with diffuse large B-cell lymphoma, primary mediastinal B-cell lymphoma, or transformed follicular lymphoma showed an objective response rate of 82% of patients – including 58% showing complete responses – after a median follow-up of 15.4 months.

In a video interview at the annual meeting of the American Society of Hematology, Sattva S. Neelapu, MD, from the University of Texas MD Anderson Cancer Center in Houston discusses the use of CAR T cells directed against the CD19 antigen in patients with relapsed/refractory B-cell lymphomas and describes efforts to improve responses while managing adverse events common to CAR T-cell therapies, notably cytokine release syndrome.

ZUMA-1 is supported by Kite Pharma, which developed axicabtagene ciloleucel, and the Leukemia & Lymphoma Society’s Therapy Acceleration Program. Dr. Neelapu reported receiving advisory board fees from the company.

SAN ANTONIO – Although the initial ardor over the use of circulating tumor cells (CTCs) in cancer diagnosis has cooled, new research suggests that they may play a role in identifying late breast cancer recurrences in otherwise asymptomatic patients, according to members of the ECOG-ACRIN cancer research group.

In this video interview from the the San Antonio Breast Cancer Symposium, Joseph A. Sparano, MD, of Montefiore Medical Center and Albert Einstein College of Medicine in New York, describes ECOG-ACRIN’s experiments showing that patients with hormone receptor–positive disease and HER2-negative breast cancer have a significantly elevated risk for recurrence, supporting CTCs as prognostic biomarkers for late recurrences.

If the findings can be replicated in prospective clinical trials, CTC assay results could help clinicians choose treatments for patients who are at risk for late recurrence.

ECOG-ACRIN received funding for this study from the Breast Cancer Research Foundation, Susan G. Komen, and the National Cancer Institute. Dr. Sparano declared no conflicts of interest.

SAN ANTONIO – Although the initial ardor over the use of circulating tumor cells (CTCs) in cancer diagnosis has cooled, new research suggests that they may play a role in identifying late breast cancer recurrences in otherwise asymptomatic patients, according to members of the ECOG-ACRIN cancer research group.

In this video interview from the the San Antonio Breast Cancer Symposium, Joseph A. Sparano, MD, of Montefiore Medical Center and Albert Einstein College of Medicine in New York, describes ECOG-ACRIN’s experiments showing that patients with hormone receptor–positive disease and HER2-negative breast cancer have a significantly elevated risk for recurrence, supporting CTCs as prognostic biomarkers for late recurrences.

If the findings can be replicated in prospective clinical trials, CTC assay results could help clinicians choose treatments for patients who are at risk for late recurrence.

ECOG-ACRIN received funding for this study from the Breast Cancer Research Foundation, Susan G. Komen, and the National Cancer Institute. Dr. Sparano declared no conflicts of interest.

SAN ANTONIO – Although the initial ardor over the use of circulating tumor cells (CTCs) in cancer diagnosis has cooled, new research suggests that they may play a role in identifying late breast cancer recurrences in otherwise asymptomatic patients, according to members of the ECOG-ACRIN cancer research group.

In this video interview from the the San Antonio Breast Cancer Symposium, Joseph A. Sparano, MD, of Montefiore Medical Center and Albert Einstein College of Medicine in New York, describes ECOG-ACRIN’s experiments showing that patients with hormone receptor–positive disease and HER2-negative breast cancer have a significantly elevated risk for recurrence, supporting CTCs as prognostic biomarkers for late recurrences.

If the findings can be replicated in prospective clinical trials, CTC assay results could help clinicians choose treatments for patients who are at risk for late recurrence.

ECOG-ACRIN received funding for this study from the Breast Cancer Research Foundation, Susan G. Komen, and the National Cancer Institute. Dr. Sparano declared no conflicts of interest.

ATLANTA – More than one-third of patients with refractory large B-cell lymphomas treated with the chimeric antigen receptor (CAR) T-cell product axicabtagene ciloleucel (Yescarta), often called axi-cel, had durable responses, with some patients having complete responses lasting more than 1 year after a single infusion, according to investigators in the ZUMA-1 trial.

Neil Osterweil/Frontline Medical News

Updated combined phase 1 and phase 2 results in 108 patients with diffuse large B-cell lymphoma (DLBCL), primary mediastinal B-cell lymphoma (PMBCL), or transformed follicular lymphoma (TFL) showed an objective response rate (ORR) of 82%, including 58% complete responses, after a median follow-up of 15.4 months, reported Sattva S. Neelapu, MD, from the University of Texas MD Anderson Cancer Center in Houston.

“Axi-cel is highly effective in patients with large B-cell lymphoma who otherwise have no curative treatment options,” he said in a briefing at the annual meeting of the American Society of Hematology, prior to his presentation of the data in an oral session.

The trial results were also published simultaneously in the New England Journal of Medicine.As previously reported, in the multicenter phase 2 ZUMA-1 trial, 111 patients with treatment refractory DLBCL, PMBCL, or TFL were enrolled and treated with axi-cel at a target dose of 2 x 10⁶ cells/kg, following a conditioning regimen with low-dose cyclophosphamide and fludarabine.

The median patient age was 58 years. Patients had stage III or IV disease, 48% had International Prognostic Index scores of 3-4, 76% had disease that was refractory to third-line therapies or beyond, and 21% had disease that relapsed within 12 months of an autologous bone marrow transplant

Axi-cel was successfully manufactured with sufficient cells for transfusion in all but one of the 111 patients, and 101 patients eventually received infusions in phase 2 (modified intention-to-treat population). The average turnaround time from apheresis to the clinical site was 17 days.

Dr. Neelapu also presented data on seven patients enrolled in phase 1; the data were combined with the phase 2 results for an updated analysis of those patients who had at least 1 year of follow-up.

The phase 2 trial met its primary endpoint at the time of the primary analysis, with an 82% ORR, consisting of 54% complete responses and 28% partial responses at a median follow-up of 8.7 months.

In the updated analysis, the ORR and respective remission rates were 82%, 58%, and 34%, at a median of 15.4 months follow-up.

The median duration of response in the updated analysis was 11.1 months. The median duration of complete responses had not been reached at the time of data cutoff in August 2017. The median duration of partial responses was 1.9 months.

At the 15.4-month mark, 42% of patients remained free of disease progression, and 56% were alive, with the median overall survival not yet reached.

The treatment had generally acceptable toxicities, with only 13% of patients in phase 2 experiencing grade 3 or greater cytokine release syndrome (CRS), although one patient with CRS died from hemophagocytic lymphohistiocytosis, and one with CRS died from cardiac arrest. Grade 3 or greater neurologic events occurred in 28% of patients, and included encephalopathy, confusional state, aphasia, and somnolence.

The events were generally reversible, and the rates of each declined over time. The use of tocilizumab or steroids to control adverse events did not have a negative effect on responses.

Since the primary analysis with at least 6 months of follow-up, there have been no new axi-cel–related cases of CRS, neurologic events, or deaths.

Dr. Neelapu also presented safety data on serious adverse events occurring more than 6 months after therapy in 10 patients who developed symptoms after the data cutoff.

Grade 3 events in these patients included lung infection, recurrent upper respiratory viral infection, and rotavirus infection, pneumonias, atrial fibrillation with rapid ventricular response, lung infection, febrile neutropenia, and influenza B infection. One patient had grade 4 sepsis.

In an editorial accompanying the study in the New England Journal of Medicine, Eric Tran, PhD, and Walter J. Urba, MD, PhD, from the Earle A. Chiles Research Institute and the Providence Portland (Ore.) Medical Center, and Dan L. Longo, MD, deputy editor of the journal, praised ZUMA-1 as “a landmark study because it involved 22 institutions and showed that a personalized gene-engineered T-cell product could be rapidly generated at a centralized cell-manufacturing facility and safely administered to patients at transplantation-capable medical centers.”

They noted, however, that about half of all patients with relapsed or refractory large B-cell lymphomas will not have durable responses to CAR T-cell therapy directed against CD19, and that new strategies will be needed to improve responses (N Engl J Med. 2017 Dec 10; doi: 10.1056/NEJMe1714680).

In the question and answer session at the end of the briefing, Dr. Neelapu said the preliminary observations of mechanisms of relapse or disease progression in some patients may be related to the loss of the CD19 antigen, which occurs in about one-third of patients who experience relapse, and to high expression of the programmed death ligand-1, which can potentially inhibit CAR-T cell function. A clinical trial is currently underway to evaluate potential strategies for improving response rates to CAR-T therapies, he said.

ZUMA-1 is supported by Kite Pharma and the Leukemia and Lymphoma Society Therapy Acceleration Program. Dr. Neelapu reported receiving advisory board fees from the company. Myriad coauthors also reported financial relationship with multiple companies.

SOURCE: Neelapu S et al. ASH 2017 Abstract 578.

ATLANTA – More than one-third of patients with refractory large B-cell lymphomas treated with the chimeric antigen receptor (CAR) T-cell product axicabtagene ciloleucel (Yescarta), often called axi-cel, had durable responses, with some patients having complete responses lasting more than 1 year after a single infusion, according to investigators in the ZUMA-1 trial.

Neil Osterweil/Frontline Medical News

Updated combined phase 1 and phase 2 results in 108 patients with diffuse large B-cell lymphoma (DLBCL), primary mediastinal B-cell lymphoma (PMBCL), or transformed follicular lymphoma (TFL) showed an objective response rate (ORR) of 82%, including 58% complete responses, after a median follow-up of 15.4 months, reported Sattva S. Neelapu, MD, from the University of Texas MD Anderson Cancer Center in Houston.

“Axi-cel is highly effective in patients with large B-cell lymphoma who otherwise have no curative treatment options,” he said in a briefing at the annual meeting of the American Society of Hematology, prior to his presentation of the data in an oral session.

The trial results were also published simultaneously in the New England Journal of Medicine.As previously reported, in the multicenter phase 2 ZUMA-1 trial, 111 patients with treatment refractory DLBCL, PMBCL, or TFL were enrolled and treated with axi-cel at a target dose of 2 x 10⁶ cells/kg, following a conditioning regimen with low-dose cyclophosphamide and fludarabine.

The median patient age was 58 years. Patients had stage III or IV disease, 48% had International Prognostic Index scores of 3-4, 76% had disease that was refractory to third-line therapies or beyond, and 21% had disease that relapsed within 12 months of an autologous bone marrow transplant

Axi-cel was successfully manufactured with sufficient cells for transfusion in all but one of the 111 patients, and 101 patients eventually received infusions in phase 2 (modified intention-to-treat population). The average turnaround time from apheresis to the clinical site was 17 days.

Dr. Neelapu also presented data on seven patients enrolled in phase 1; the data were combined with the phase 2 results for an updated analysis of those patients who had at least 1 year of follow-up.

The phase 2 trial met its primary endpoint at the time of the primary analysis, with an 82% ORR, consisting of 54% complete responses and 28% partial responses at a median follow-up of 8.7 months.

In the updated analysis, the ORR and respective remission rates were 82%, 58%, and 34%, at a median of 15.4 months follow-up.

The median duration of response in the updated analysis was 11.1 months. The median duration of complete responses had not been reached at the time of data cutoff in August 2017. The median duration of partial responses was 1.9 months.

At the 15.4-month mark, 42% of patients remained free of disease progression, and 56% were alive, with the median overall survival not yet reached.

The treatment had generally acceptable toxicities, with only 13% of patients in phase 2 experiencing grade 3 or greater cytokine release syndrome (CRS), although one patient with CRS died from hemophagocytic lymphohistiocytosis, and one with CRS died from cardiac arrest. Grade 3 or greater neurologic events occurred in 28% of patients, and included encephalopathy, confusional state, aphasia, and somnolence.

The events were generally reversible, and the rates of each declined over time. The use of tocilizumab or steroids to control adverse events did not have a negative effect on responses.

Since the primary analysis with at least 6 months of follow-up, there have been no new axi-cel–related cases of CRS, neurologic events, or deaths.

Dr. Neelapu also presented safety data on serious adverse events occurring more than 6 months after therapy in 10 patients who developed symptoms after the data cutoff.

Grade 3 events in these patients included lung infection, recurrent upper respiratory viral infection, and rotavirus infection, pneumonias, atrial fibrillation with rapid ventricular response, lung infection, febrile neutropenia, and influenza B infection. One patient had grade 4 sepsis.

In an editorial accompanying the study in the New England Journal of Medicine, Eric Tran, PhD, and Walter J. Urba, MD, PhD, from the Earle A. Chiles Research Institute and the Providence Portland (Ore.) Medical Center, and Dan L. Longo, MD, deputy editor of the journal, praised ZUMA-1 as “a landmark study because it involved 22 institutions and showed that a personalized gene-engineered T-cell product could be rapidly generated at a centralized cell-manufacturing facility and safely administered to patients at transplantation-capable medical centers.”

They noted, however, that about half of all patients with relapsed or refractory large B-cell lymphomas will not have durable responses to CAR T-cell therapy directed against CD19, and that new strategies will be needed to improve responses (N Engl J Med. 2017 Dec 10; doi: 10.1056/NEJMe1714680).

In the question and answer session at the end of the briefing, Dr. Neelapu said the preliminary observations of mechanisms of relapse or disease progression in some patients may be related to the loss of the CD19 antigen, which occurs in about one-third of patients who experience relapse, and to high expression of the programmed death ligand-1, which can potentially inhibit CAR-T cell function. A clinical trial is currently underway to evaluate potential strategies for improving response rates to CAR-T therapies, he said.

ZUMA-1 is supported by Kite Pharma and the Leukemia and Lymphoma Society Therapy Acceleration Program. Dr. Neelapu reported receiving advisory board fees from the company. Myriad coauthors also reported financial relationship with multiple companies.

SOURCE: Neelapu S et al. ASH 2017 Abstract 578.

ATLANTA – More than one-third of patients with refractory large B-cell lymphomas treated with the chimeric antigen receptor (CAR) T-cell product axicabtagene ciloleucel (Yescarta), often called axi-cel, had durable responses, with some patients having complete responses lasting more than 1 year after a single infusion, according to investigators in the ZUMA-1 trial.

Neil Osterweil/Frontline Medical News

Updated combined phase 1 and phase 2 results in 108 patients with diffuse large B-cell lymphoma (DLBCL), primary mediastinal B-cell lymphoma (PMBCL), or transformed follicular lymphoma (TFL) showed an objective response rate (ORR) of 82%, including 58% complete responses, after a median follow-up of 15.4 months, reported Sattva S. Neelapu, MD, from the University of Texas MD Anderson Cancer Center in Houston.

“Axi-cel is highly effective in patients with large B-cell lymphoma who otherwise have no curative treatment options,” he said in a briefing at the annual meeting of the American Society of Hematology, prior to his presentation of the data in an oral session.

The trial results were also published simultaneously in the New England Journal of Medicine.As previously reported, in the multicenter phase 2 ZUMA-1 trial, 111 patients with treatment refractory DLBCL, PMBCL, or TFL were enrolled and treated with axi-cel at a target dose of 2 x 10⁶ cells/kg, following a conditioning regimen with low-dose cyclophosphamide and fludarabine.

The median patient age was 58 years. Patients had stage III or IV disease, 48% had International Prognostic Index scores of 3-4, 76% had disease that was refractory to third-line therapies or beyond, and 21% had disease that relapsed within 12 months of an autologous bone marrow transplant

Axi-cel was successfully manufactured with sufficient cells for transfusion in all but one of the 111 patients, and 101 patients eventually received infusions in phase 2 (modified intention-to-treat population). The average turnaround time from apheresis to the clinical site was 17 days.

Dr. Neelapu also presented data on seven patients enrolled in phase 1; the data were combined with the phase 2 results for an updated analysis of those patients who had at least 1 year of follow-up.

The phase 2 trial met its primary endpoint at the time of the primary analysis, with an 82% ORR, consisting of 54% complete responses and 28% partial responses at a median follow-up of 8.7 months.

In the updated analysis, the ORR and respective remission rates were 82%, 58%, and 34%, at a median of 15.4 months follow-up.

The median duration of response in the updated analysis was 11.1 months. The median duration of complete responses had not been reached at the time of data cutoff in August 2017. The median duration of partial responses was 1.9 months.

At the 15.4-month mark, 42% of patients remained free of disease progression, and 56% were alive, with the median overall survival not yet reached.

The treatment had generally acceptable toxicities, with only 13% of patients in phase 2 experiencing grade 3 or greater cytokine release syndrome (CRS), although one patient with CRS died from hemophagocytic lymphohistiocytosis, and one with CRS died from cardiac arrest. Grade 3 or greater neurologic events occurred in 28% of patients, and included encephalopathy, confusional state, aphasia, and somnolence.

The events were generally reversible, and the rates of each declined over time. The use of tocilizumab or steroids to control adverse events did not have a negative effect on responses.

Since the primary analysis with at least 6 months of follow-up, there have been no new axi-cel–related cases of CRS, neurologic events, or deaths.

Dr. Neelapu also presented safety data on serious adverse events occurring more than 6 months after therapy in 10 patients who developed symptoms after the data cutoff.

Grade 3 events in these patients included lung infection, recurrent upper respiratory viral infection, and rotavirus infection, pneumonias, atrial fibrillation with rapid ventricular response, lung infection, febrile neutropenia, and influenza B infection. One patient had grade 4 sepsis.

In an editorial accompanying the study in the New England Journal of Medicine, Eric Tran, PhD, and Walter J. Urba, MD, PhD, from the Earle A. Chiles Research Institute and the Providence Portland (Ore.) Medical Center, and Dan L. Longo, MD, deputy editor of the journal, praised ZUMA-1 as “a landmark study because it involved 22 institutions and showed that a personalized gene-engineered T-cell product could be rapidly generated at a centralized cell-manufacturing facility and safely administered to patients at transplantation-capable medical centers.”

They noted, however, that about half of all patients with relapsed or refractory large B-cell lymphomas will not have durable responses to CAR T-cell therapy directed against CD19, and that new strategies will be needed to improve responses (N Engl J Med. 2017 Dec 10; doi: 10.1056/NEJMe1714680).

In the question and answer session at the end of the briefing, Dr. Neelapu said the preliminary observations of mechanisms of relapse or disease progression in some patients may be related to the loss of the CD19 antigen, which occurs in about one-third of patients who experience relapse, and to high expression of the programmed death ligand-1, which can potentially inhibit CAR-T cell function. A clinical trial is currently underway to evaluate potential strategies for improving response rates to CAR-T therapies, he said.

ZUMA-1 is supported by Kite Pharma and the Leukemia and Lymphoma Society Therapy Acceleration Program. Dr. Neelapu reported receiving advisory board fees from the company. Myriad coauthors also reported financial relationship with multiple companies.

SOURCE: Neelapu S et al. ASH 2017 Abstract 578.

ATLANTA – Matching red cell products to sickle-cell disease (SCD) patients with rare Rh antibodies can be accomplished with a little fancy stem cell footwork and some genetic legerdemain, investigators report.

With the help of CRISPR/Cas9 gene-editing, Stella T. Chou, MD, from Children’s Hospital of Philadelphia and her colleagues have created a panel of red cell reagents customized from induced pluripotent stem cells (iPSCs) to produce a renewable source of red cell reagents and potentially universal infusion products for patients with SCD.

“It has been more than 10 years since iPSCs have been available, but we have yet to see applications for blood diseases that improve how we care for our patients,” Dr. Chou said in a statement. “Using this panel, we would be able to more quickly identify what antibodies the patient has made, informing us what kind of blood we have to give them. It means we’ll be able to improve their ability to be transfused safely and reduce delays in their care.”

Up to half of all patients with SCD who require chronic transfusions may develop antibodies to allogeneic blood products, but identifying inactivating antibodies in a given patient can be both challenging and time consuming, due to a paucity of the appropriate reagent red cells, Dr. Chou and her colleagues reported.

The investigators previously reported that despite receiving transfusions from Rh-matched minority donors, patients with SCD have a high prevalence of red blood cell alloimmunization, and that Rh antibodies are the most common type of antibody in SCD patients, with about 33% of Rh antibodies associated with delayed transfusion reactions (Blood. 2013 Aug 8;122:1062-71; doi: 10.1182/blood-2013-03-490623).

It is both costly and time consuming to genotype donated blood for Rh antigens in order to match a low-antigen product to a specific patient. Instead, the investigators identified a workaround involving reprogramming or genetically engineering iPSCs from donors with rare antigen profiles, with the goal of creating a standard panel of red cell reagents that could reliably and quickly identify SCD patients with complex antibodies.

They used CRISPR/Cas9 gene-editing techniques to modify existing iPSCs to include Rh null cells, other cells lacking all or part of certain high-prevalence Rh antigens, and low prevalence novel antigens.

The investigators then showed that they could induce hematopoietic differentiation of their customized iPSCs through a three-step process and demonstrated that, as they had expected, the engineered antibodies were able to more accurately type Rh in gel card assays than did off-the-shelf commercial assays.

“We have designed a panel of customized iPSCs reprogrammed from rare donors or genetically engineered to express rare blood group antigen phenotypes or combinations that are difficult or impossible to find as donor red cells. Any number of combinations not found in natural populations can be produced and generated in quantities sufficient for reagents,” Dr. Chou said.

They also asserted that iPSC-derived red blood cells (iRBCs) produced from their customized iPSCs could be used with standard blood bank assays as a potential means of streamlining and standardizing the antibody identification process in alloimmunized patients with complex antibody specificities.

“In the future, when technology for scale-up is available, Rh null iRBCs could be used as ‘universal’ donor cells for future therapeutic applications,” the reseachers wrote.

The study was supported by the National Institutes of Health/National Heart Lung and Blood Institute. The authors reported having no conflicts of interest.

SOURCE: Chou S et al. ASH 2017 Abstract 3

ATLANTA – Matching red cell products to sickle-cell disease (SCD) patients with rare Rh antibodies can be accomplished with a little fancy stem cell footwork and some genetic legerdemain, investigators report.

With the help of CRISPR/Cas9 gene-editing, Stella T. Chou, MD, from Children’s Hospital of Philadelphia and her colleagues have created a panel of red cell reagents customized from induced pluripotent stem cells (iPSCs) to produce a renewable source of red cell reagents and potentially universal infusion products for patients with SCD.

“It has been more than 10 years since iPSCs have been available, but we have yet to see applications for blood diseases that improve how we care for our patients,” Dr. Chou said in a statement. “Using this panel, we would be able to more quickly identify what antibodies the patient has made, informing us what kind of blood we have to give them. It means we’ll be able to improve their ability to be transfused safely and reduce delays in their care.”

Up to half of all patients with SCD who require chronic transfusions may develop antibodies to allogeneic blood products, but identifying inactivating antibodies in a given patient can be both challenging and time consuming, due to a paucity of the appropriate reagent red cells, Dr. Chou and her colleagues reported.

The investigators previously reported that despite receiving transfusions from Rh-matched minority donors, patients with SCD have a high prevalence of red blood cell alloimmunization, and that Rh antibodies are the most common type of antibody in SCD patients, with about 33% of Rh antibodies associated with delayed transfusion reactions (Blood. 2013 Aug 8;122:1062-71; doi: 10.1182/blood-2013-03-490623).

It is both costly and time consuming to genotype donated blood for Rh antigens in order to match a low-antigen product to a specific patient. Instead, the investigators identified a workaround involving reprogramming or genetically engineering iPSCs from donors with rare antigen profiles, with the goal of creating a standard panel of red cell reagents that could reliably and quickly identify SCD patients with complex antibodies.

They used CRISPR/Cas9 gene-editing techniques to modify existing iPSCs to include Rh null cells, other cells lacking all or part of certain high-prevalence Rh antigens, and low prevalence novel antigens.

The investigators then showed that they could induce hematopoietic differentiation of their customized iPSCs through a three-step process and demonstrated that, as they had expected, the engineered antibodies were able to more accurately type Rh in gel card assays than did off-the-shelf commercial assays.

“We have designed a panel of customized iPSCs reprogrammed from rare donors or genetically engineered to express rare blood group antigen phenotypes or combinations that are difficult or impossible to find as donor red cells. Any number of combinations not found in natural populations can be produced and generated in quantities sufficient for reagents,” Dr. Chou said.

They also asserted that iPSC-derived red blood cells (iRBCs) produced from their customized iPSCs could be used with standard blood bank assays as a potential means of streamlining and standardizing the antibody identification process in alloimmunized patients with complex antibody specificities.

“In the future, when technology for scale-up is available, Rh null iRBCs could be used as ‘universal’ donor cells for future therapeutic applications,” the reseachers wrote.

The study was supported by the National Institutes of Health/National Heart Lung and Blood Institute. The authors reported having no conflicts of interest.

SOURCE: Chou S et al. ASH 2017 Abstract 3

ATLANTA – Matching red cell products to sickle-cell disease (SCD) patients with rare Rh antibodies can be accomplished with a little fancy stem cell footwork and some genetic legerdemain, investigators report.

With the help of CRISPR/Cas9 gene-editing, Stella T. Chou, MD, from Children’s Hospital of Philadelphia and her colleagues have created a panel of red cell reagents customized from induced pluripotent stem cells (iPSCs) to produce a renewable source of red cell reagents and potentially universal infusion products for patients with SCD.

“It has been more than 10 years since iPSCs have been available, but we have yet to see applications for blood diseases that improve how we care for our patients,” Dr. Chou said in a statement. “Using this panel, we would be able to more quickly identify what antibodies the patient has made, informing us what kind of blood we have to give them. It means we’ll be able to improve their ability to be transfused safely and reduce delays in their care.”

Up to half of all patients with SCD who require chronic transfusions may develop antibodies to allogeneic blood products, but identifying inactivating antibodies in a given patient can be both challenging and time consuming, due to a paucity of the appropriate reagent red cells, Dr. Chou and her colleagues reported.

The investigators previously reported that despite receiving transfusions from Rh-matched minority donors, patients with SCD have a high prevalence of red blood cell alloimmunization, and that Rh antibodies are the most common type of antibody in SCD patients, with about 33% of Rh antibodies associated with delayed transfusion reactions (Blood. 2013 Aug 8;122:1062-71; doi: 10.1182/blood-2013-03-490623).

It is both costly and time consuming to genotype donated blood for Rh antigens in order to match a low-antigen product to a specific patient. Instead, the investigators identified a workaround involving reprogramming or genetically engineering iPSCs from donors with rare antigen profiles, with the goal of creating a standard panel of red cell reagents that could reliably and quickly identify SCD patients with complex antibodies.

They used CRISPR/Cas9 gene-editing techniques to modify existing iPSCs to include Rh null cells, other cells lacking all or part of certain high-prevalence Rh antigens, and low prevalence novel antigens.

The investigators then showed that they could induce hematopoietic differentiation of their customized iPSCs through a three-step process and demonstrated that, as they had expected, the engineered antibodies were able to more accurately type Rh in gel card assays than did off-the-shelf commercial assays.

“We have designed a panel of customized iPSCs reprogrammed from rare donors or genetically engineered to express rare blood group antigen phenotypes or combinations that are difficult or impossible to find as donor red cells. Any number of combinations not found in natural populations can be produced and generated in quantities sufficient for reagents,” Dr. Chou said.

They also asserted that iPSC-derived red blood cells (iRBCs) produced from their customized iPSCs could be used with standard blood bank assays as a potential means of streamlining and standardizing the antibody identification process in alloimmunized patients with complex antibody specificities.

“In the future, when technology for scale-up is available, Rh null iRBCs could be used as ‘universal’ donor cells for future therapeutic applications,” the reseachers wrote.

The study was supported by the National Institutes of Health/National Heart Lung and Blood Institute. The authors reported having no conflicts of interest.

SOURCE: Chou S et al. ASH 2017 Abstract 3

SAN ANTONIO – In women with advanced HER2-negative breast cancer with germline BRCA mutations, talazoparib, an investigational oral PARP inhibitor, was associated with a near doubling in progression-free survival, compared with single-agent chemotherapy in the phase 3 EMBRACA trial.

After a median follow-up of 11.2 months, median progression-free survival by blinded central review was 8.6 months for patients assigned to receive talazoparib, compared with 5.6 months for patients randomized to receive the physician’s choice of either capecitabine, eribulin, gemcitabine, or vinorelbine.

In this video interview from the San Antonio Breast Cancer Symposium, Jennifer K. Litton, MD, from the University of Texas MD Anderson Cancer Center in Houston discusses the comparative efficacy of the drug relative to standard chemotherapy agents in this population, and the association of the PARP inhibitor with improved patient-reported quality of life outcomes.

The EMBRACA study was funded by Pfizer. Dr. Litton has disclosed research funding with EMD Serono, AstraZeneca, Pfizer, Genentech, and GlaxoSmithKline, and serves on advisory boards for Pfizer and AstraZeneca, all uncompensated.

SAN ANTONIO – In women with advanced HER2-negative breast cancer with germline BRCA mutations, talazoparib, an investigational oral PARP inhibitor, was associated with a near doubling in progression-free survival, compared with single-agent chemotherapy in the phase 3 EMBRACA trial.

After a median follow-up of 11.2 months, median progression-free survival by blinded central review was 8.6 months for patients assigned to receive talazoparib, compared with 5.6 months for patients randomized to receive the physician’s choice of either capecitabine, eribulin, gemcitabine, or vinorelbine.

In this video interview from the San Antonio Breast Cancer Symposium, Jennifer K. Litton, MD, from the University of Texas MD Anderson Cancer Center in Houston discusses the comparative efficacy of the drug relative to standard chemotherapy agents in this population, and the association of the PARP inhibitor with improved patient-reported quality of life outcomes.

The EMBRACA study was funded by Pfizer. Dr. Litton has disclosed research funding with EMD Serono, AstraZeneca, Pfizer, Genentech, and GlaxoSmithKline, and serves on advisory boards for Pfizer and AstraZeneca, all uncompensated.

SAN ANTONIO – In women with advanced HER2-negative breast cancer with germline BRCA mutations, talazoparib, an investigational oral PARP inhibitor, was associated with a near doubling in progression-free survival, compared with single-agent chemotherapy in the phase 3 EMBRACA trial.

After a median follow-up of 11.2 months, median progression-free survival by blinded central review was 8.6 months for patients assigned to receive talazoparib, compared with 5.6 months for patients randomized to receive the physician’s choice of either capecitabine, eribulin, gemcitabine, or vinorelbine.

In this video interview from the San Antonio Breast Cancer Symposium, Jennifer K. Litton, MD, from the University of Texas MD Anderson Cancer Center in Houston discusses the comparative efficacy of the drug relative to standard chemotherapy agents in this population, and the association of the PARP inhibitor with improved patient-reported quality of life outcomes.

The EMBRACA study was funded by Pfizer. Dr. Litton has disclosed research funding with EMD Serono, AstraZeneca, Pfizer, Genentech, and GlaxoSmithKline, and serves on advisory boards for Pfizer and AstraZeneca, all uncompensated.

SAN ANTONIO – Five years of additional therapy with anastrozole (Arimidex) was no more effective than 2 additional years following the standard 5 years of initial endocrine therapy in postmenopausal women with hormone receptor–positive (HR+) breast cancer, Austrian investigators reported.

In fact, the only thing that the additional years of the aromatase inhibitor (AI) anastrozole seemed to add was increased risk for fracture, said Michael Gnant, MD, from the Medical University of Vienna, on behalf of colleagues in the ABCSG-16 trial.

SOURCE: Gnant et al. SABCS 2017 Abstract GS3-01

SAN ANTONIO – Five years of additional therapy with anastrozole (Arimidex) was no more effective than 2 additional years following the standard 5 years of initial endocrine therapy in postmenopausal women with hormone receptor–positive (HR+) breast cancer, Austrian investigators reported.

In fact, the only thing that the additional years of the aromatase inhibitor (AI) anastrozole seemed to add was increased risk for fracture, said Michael Gnant, MD, from the Medical University of Vienna, on behalf of colleagues in the ABCSG-16 trial.

SOURCE: Gnant et al. SABCS 2017 Abstract GS3-01

SAN ANTONIO – Five years of additional therapy with anastrozole (Arimidex) was no more effective than 2 additional years following the standard 5 years of initial endocrine therapy in postmenopausal women with hormone receptor–positive (HR+) breast cancer, Austrian investigators reported.

In fact, the only thing that the additional years of the aromatase inhibitor (AI) anastrozole seemed to add was increased risk for fracture, said Michael Gnant, MD, from the Medical University of Vienna, on behalf of colleagues in the ABCSG-16 trial.

SOURCE: Gnant et al. SABCS 2017 Abstract GS3-01

SAN ANTONIO – For premenopausal women with advanced hormone receptor–positive, HER2-negative breast cancer, the addition of the cyclin-dependent kinase (CDK) 4/6 inhibitor ribociclib (Kisqali) to endocrine therapy and goserelin was associated with a near doubling in progression-free survival (PFS), improvement in pain scores and a longer time to deterioration of quality of life scores.

Previous clinical trials have shown the advantage of adding a CDK4/6 inhibitor to standard aromatase inhibitor therapy in postmenopausal women, but the randomized phase 3 MONALEESA-7 trial is the first phase 3 study of an agent in this class in premenopausal women with breast cancer, and is the first randomized trial in this population in nearly 2 decades, notes Debu Tripathy, MD, from the University of Texas MD Anderson Cancer Center in Houston.

The median PFS for women treated with ribociclib plus endocrine therapy with either an aromatase inhibitor or tamoxifen plus the lutenizing hormone-releasing hormone agonist goserelin was 23.8 months, compared with 13 months for women treated with the same combination except for a ribociclib placebo.

In this video interview at the San Antonio Breast Cancer Symposium, Dr. Tripathy discusses the therapeutic benefits and quality of life improvements associated with adding ribociclib to endocrine therapy and ovarian suppression in this population.

The MONALEESA 7 trial was supported by Novartis. Dr. Tripathy disclosed steering committee consulting fees and institutional funding from the company.

op@frontlinemedcom.com

SAN ANTONIO – For premenopausal women with advanced hormone receptor–positive, HER2-negative breast cancer, the addition of the cyclin-dependent kinase (CDK) 4/6 inhibitor ribociclib (Kisqali) to endocrine therapy and goserelin was associated with a near doubling in progression-free survival (PFS), improvement in pain scores and a longer time to deterioration of quality of life scores.

Previous clinical trials have shown the advantage of adding a CDK4/6 inhibitor to standard aromatase inhibitor therapy in postmenopausal women, but the randomized phase 3 MONALEESA-7 trial is the first phase 3 study of an agent in this class in premenopausal women with breast cancer, and is the first randomized trial in this population in nearly 2 decades, notes Debu Tripathy, MD, from the University of Texas MD Anderson Cancer Center in Houston.

The median PFS for women treated with ribociclib plus endocrine therapy with either an aromatase inhibitor or tamoxifen plus the lutenizing hormone-releasing hormone agonist goserelin was 23.8 months, compared with 13 months for women treated with the same combination except for a ribociclib placebo.

In this video interview at the San Antonio Breast Cancer Symposium, Dr. Tripathy discusses the therapeutic benefits and quality of life improvements associated with adding ribociclib to endocrine therapy and ovarian suppression in this population.

The MONALEESA 7 trial was supported by Novartis. Dr. Tripathy disclosed steering committee consulting fees and institutional funding from the company.

op@frontlinemedcom.com

SAN ANTONIO – For premenopausal women with advanced hormone receptor–positive, HER2-negative breast cancer, the addition of the cyclin-dependent kinase (CDK) 4/6 inhibitor ribociclib (Kisqali) to endocrine therapy and goserelin was associated with a near doubling in progression-free survival (PFS), improvement in pain scores and a longer time to deterioration of quality of life scores.

Previous clinical trials have shown the advantage of adding a CDK4/6 inhibitor to standard aromatase inhibitor therapy in postmenopausal women, but the randomized phase 3 MONALEESA-7 trial is the first phase 3 study of an agent in this class in premenopausal women with breast cancer, and is the first randomized trial in this population in nearly 2 decades, notes Debu Tripathy, MD, from the University of Texas MD Anderson Cancer Center in Houston.

The median PFS for women treated with ribociclib plus endocrine therapy with either an aromatase inhibitor or tamoxifen plus the lutenizing hormone-releasing hormone agonist goserelin was 23.8 months, compared with 13 months for women treated with the same combination except for a ribociclib placebo.

In this video interview at the San Antonio Breast Cancer Symposium, Dr. Tripathy discusses the therapeutic benefits and quality of life improvements associated with adding ribociclib to endocrine therapy and ovarian suppression in this population.

The MONALEESA 7 trial was supported by Novartis. Dr. Tripathy disclosed steering committee consulting fees and institutional funding from the company.

op@frontlinemedcom.com

SAN ANTONIO – Clinical trials have shown a clear benefit for preventing breast cancer recurrence with aromatase inhibitor (AI) therapy following 5 years of tamoxifen. Yet the optimal duration for additional AI therapy following 5 years of endocrine therapy with tamoxifen, an AI, or sequential therapies is not known, according to Michael Gnant, MD, from the Medical University of Vienna.

In the ABCSG-16 trial, Dr. Gnant and his colleagues reported that 5 years of additional therapy with anastrozole (Arimidex) was no more effective than 2 additional years following the standard 5 years of initial endocrine therapy in postmenopausal women with hormone receptor–positive (HR+) breast cancer.

In this video interview at the San Antonio Breast Cancer Symposium, Dr. Gnant notes that, although some patients may still benefit from 5 years of additional therapy, the trial results suggest that most patients can be spared from such adverse events as risk for fractures associated with three additional and evidently unnecessary years of therapy.

The ABCSG-16 study was supported by AstraZeneca. Dr. Gnant disclosed research funding, honoraria, and travel funding from the company and others.

op@frontlinemedcom.com

SAN ANTONIO – Clinical trials have shown a clear benefit for preventing breast cancer recurrence with aromatase inhibitor (AI) therapy following 5 years of tamoxifen. Yet the optimal duration for additional AI therapy following 5 years of endocrine therapy with tamoxifen, an AI, or sequential therapies is not known, according to Michael Gnant, MD, from the Medical University of Vienna.

In the ABCSG-16 trial, Dr. Gnant and his colleagues reported that 5 years of additional therapy with anastrozole (Arimidex) was no more effective than 2 additional years following the standard 5 years of initial endocrine therapy in postmenopausal women with hormone receptor–positive (HR+) breast cancer.

In this video interview at the San Antonio Breast Cancer Symposium, Dr. Gnant notes that, although some patients may still benefit from 5 years of additional therapy, the trial results suggest that most patients can be spared from such adverse events as risk for fractures associated with three additional and evidently unnecessary years of therapy.

The ABCSG-16 study was supported by AstraZeneca. Dr. Gnant disclosed research funding, honoraria, and travel funding from the company and others.

op@frontlinemedcom.com

SAN ANTONIO – Clinical trials have shown a clear benefit for preventing breast cancer recurrence with aromatase inhibitor (AI) therapy following 5 years of tamoxifen. Yet the optimal duration for additional AI therapy following 5 years of endocrine therapy with tamoxifen, an AI, or sequential therapies is not known, according to Michael Gnant, MD, from the Medical University of Vienna.

In the ABCSG-16 trial, Dr. Gnant and his colleagues reported that 5 years of additional therapy with anastrozole (Arimidex) was no more effective than 2 additional years following the standard 5 years of initial endocrine therapy in postmenopausal women with hormone receptor–positive (HR+) breast cancer.

In this video interview at the San Antonio Breast Cancer Symposium, Dr. Gnant notes that, although some patients may still benefit from 5 years of additional therapy, the trial results suggest that most patients can be spared from such adverse events as risk for fractures associated with three additional and evidently unnecessary years of therapy.

The ABCSG-16 study was supported by AstraZeneca. Dr. Gnant disclosed research funding, honoraria, and travel funding from the company and others.

op@frontlinemedcom.com

SAN ANTONIO – Skip the perioperative aromatase inhibitor (AI) therapy in women with early stage hormone receptor-positive breast cancer, because it doesn’t make a difference in either time to recurrence or overall survival, British investigators advise.

Among nearly 4,500 women enrolled in the POETIC trial, time to recurrence (TTR) and overall survival (OS) were similar whether patients received AI therapy within 2 weeks of surgery or did not, reported John Robertson, MD, from the University of Nottingham, England, and his colleagues.

“There is no evidence of improved clinical outcome with perioperative aromatase inhibitor therapy,” he said at the San Antonio Breast Cancer Symposium.

The trial wasn’t all for naught, however, because it also provided further evidence that measuring Ki67 levels at baseline and at 2 weeks of therapy offer significant and independent prognostic information.

“If your baseline Ki67 is low, the prognosis is good, suggesting no need for 2 weeks of AI treatment and a second Ki67 measurement,” Dr. Robertson said.

However, if the Ki67 level is 10% or higher at baseline, a Ki67 measure after 2 weeks of AI therapy can be used to guide additional therapy.

“If the 2-week Ki67 is low, patients will do relatively well, with 8.4% recurrences, and may need no additional treatment beyond standard of care. If, however, your Ki67 at 2 weeks remains high, you have a poor prognosis with an almost 20% 5-year recurrence risk, and those patients should be considered for additional chemotherapy, and/or for trials looking at new agents,” he said.

POETIC was a randomized phase 3 trial in postmenopausal women with newly diagnosed estrogen– and progesterone receptor–positive invasive breast cancer. Patients were randomized on a 2:1 basis, respectively, to either perioperative therapy with an AI (letrozole or anastrozole) for 2 weeks, surgery, and an additional 2 weeks of AI treatment, or to surgery with no perioperative therapy within a 2-week window. Patients could receive further treatment in accordance with local practice.

Of 4,486 patients randomized, 4,480 were available for analysis, including 2,528 with both baseline and 2-week Ki67 in the perioperative therapy arm, and 678 with paired Ki67 readings in the no-therapy arm.

For the primary endpoint of TTR, the curves were superimposable, with 5-year TTR of 90.9% in the perioperative AI groups, and 90.3% in the no perioperative AI group, translating into an absolute difference of only 0.52%.

Similarly, there were no differences in OS at 5 years, at 89.0% vs. 89.5%, respectively (absolute difference, 0.51%), with survival curves virtually indistinguishable from one another.

The events contributing to TTR, including local or distant recurrence and breast cancer deaths were equally distributed between the trial arms.

For patients with high baseline Ki67 values (10% or greater) at both baseline and after 2 weeks of perioperative AI therapy, the 5-year absolute risk for recurrence was 19.6%, compared with 8.9% for those with high baseline but low 2-week Ki67 levels, and 4.5% for those with low levels at both time points. The hazard ratio for patients with high Ki67 at both time points was 2.22 (P less than .001).

The POETIC trial was supported by Cancer Research UK. Dr. Robertson did not report disclosure information.

SOURCE: Robertson J et al., Abstract GS1-03

SAN ANTONIO – Skip the perioperative aromatase inhibitor (AI) therapy in women with early stage hormone receptor-positive breast cancer, because it doesn’t make a difference in either time to recurrence or overall survival, British investigators advise.

Among nearly 4,500 women enrolled in the POETIC trial, time to recurrence (TTR) and overall survival (OS) were similar whether patients received AI therapy within 2 weeks of surgery or did not, reported John Robertson, MD, from the University of Nottingham, England, and his colleagues.

“There is no evidence of improved clinical outcome with perioperative aromatase inhibitor therapy,” he said at the San Antonio Breast Cancer Symposium.

The trial wasn’t all for naught, however, because it also provided further evidence that measuring Ki67 levels at baseline and at 2 weeks of therapy offer significant and independent prognostic information.

“If your baseline Ki67 is low, the prognosis is good, suggesting no need for 2 weeks of AI treatment and a second Ki67 measurement,” Dr. Robertson said.

However, if the Ki67 level is 10% or higher at baseline, a Ki67 measure after 2 weeks of AI therapy can be used to guide additional therapy.

“If the 2-week Ki67 is low, patients will do relatively well, with 8.4% recurrences, and may need no additional treatment beyond standard of care. If, however, your Ki67 at 2 weeks remains high, you have a poor prognosis with an almost 20% 5-year recurrence risk, and those patients should be considered for additional chemotherapy, and/or for trials looking at new agents,” he said.

POETIC was a randomized phase 3 trial in postmenopausal women with newly diagnosed estrogen– and progesterone receptor–positive invasive breast cancer. Patients were randomized on a 2:1 basis, respectively, to either perioperative therapy with an AI (letrozole or anastrozole) for 2 weeks, surgery, and an additional 2 weeks of AI treatment, or to surgery with no perioperative therapy within a 2-week window. Patients could receive further treatment in accordance with local practice.

Of 4,486 patients randomized, 4,480 were available for analysis, including 2,528 with both baseline and 2-week Ki67 in the perioperative therapy arm, and 678 with paired Ki67 readings in the no-therapy arm.

For the primary endpoint of TTR, the curves were superimposable, with 5-year TTR of 90.9% in the perioperative AI groups, and 90.3% in the no perioperative AI group, translating into an absolute difference of only 0.52%.

Similarly, there were no differences in OS at 5 years, at 89.0% vs. 89.5%, respectively (absolute difference, 0.51%), with survival curves virtually indistinguishable from one another.

The events contributing to TTR, including local or distant recurrence and breast cancer deaths were equally distributed between the trial arms.

For patients with high baseline Ki67 values (10% or greater) at both baseline and after 2 weeks of perioperative AI therapy, the 5-year absolute risk for recurrence was 19.6%, compared with 8.9% for those with high baseline but low 2-week Ki67 levels, and 4.5% for those with low levels at both time points. The hazard ratio for patients with high Ki67 at both time points was 2.22 (P less than .001).

The POETIC trial was supported by Cancer Research UK. Dr. Robertson did not report disclosure information.

SOURCE: Robertson J et al., Abstract GS1-03

SAN ANTONIO – Skip the perioperative aromatase inhibitor (AI) therapy in women with early stage hormone receptor-positive breast cancer, because it doesn’t make a difference in either time to recurrence or overall survival, British investigators advise.

Among nearly 4,500 women enrolled in the POETIC trial, time to recurrence (TTR) and overall survival (OS) were similar whether patients received AI therapy within 2 weeks of surgery or did not, reported John Robertson, MD, from the University of Nottingham, England, and his colleagues.

“There is no evidence of improved clinical outcome with perioperative aromatase inhibitor therapy,” he said at the San Antonio Breast Cancer Symposium.

The trial wasn’t all for naught, however, because it also provided further evidence that measuring Ki67 levels at baseline and at 2 weeks of therapy offer significant and independent prognostic information.

“If your baseline Ki67 is low, the prognosis is good, suggesting no need for 2 weeks of AI treatment and a second Ki67 measurement,” Dr. Robertson said.

However, if the Ki67 level is 10% or higher at baseline, a Ki67 measure after 2 weeks of AI therapy can be used to guide additional therapy.

“If the 2-week Ki67 is low, patients will do relatively well, with 8.4% recurrences, and may need no additional treatment beyond standard of care. If, however, your Ki67 at 2 weeks remains high, you have a poor prognosis with an almost 20% 5-year recurrence risk, and those patients should be considered for additional chemotherapy, and/or for trials looking at new agents,” he said.

POETIC was a randomized phase 3 trial in postmenopausal women with newly diagnosed estrogen– and progesterone receptor–positive invasive breast cancer. Patients were randomized on a 2:1 basis, respectively, to either perioperative therapy with an AI (letrozole or anastrozole) for 2 weeks, surgery, and an additional 2 weeks of AI treatment, or to surgery with no perioperative therapy within a 2-week window. Patients could receive further treatment in accordance with local practice.

Of 4,486 patients randomized, 4,480 were available for analysis, including 2,528 with both baseline and 2-week Ki67 in the perioperative therapy arm, and 678 with paired Ki67 readings in the no-therapy arm.

For the primary endpoint of TTR, the curves were superimposable, with 5-year TTR of 90.9% in the perioperative AI groups, and 90.3% in the no perioperative AI group, translating into an absolute difference of only 0.52%.

Similarly, there were no differences in OS at 5 years, at 89.0% vs. 89.5%, respectively (absolute difference, 0.51%), with survival curves virtually indistinguishable from one another.

The events contributing to TTR, including local or distant recurrence and breast cancer deaths were equally distributed between the trial arms.

For patients with high baseline Ki67 values (10% or greater) at both baseline and after 2 weeks of perioperative AI therapy, the 5-year absolute risk for recurrence was 19.6%, compared with 8.9% for those with high baseline but low 2-week Ki67 levels, and 4.5% for those with low levels at both time points. The hazard ratio for patients with high Ki67 at both time points was 2.22 (P less than .001).

The POETIC trial was supported by Cancer Research UK. Dr. Robertson did not report disclosure information.

SOURCE: Robertson J et al., Abstract GS1-03

SAN ANTONIO – For premenopausal women with advanced hormone receptor–positive, HER2-negative breast cancer, the addition of the CDK4/6 inhibitor ribociclib (Kisqali) to endocrine therapy and goserelin was associated with a near doubling in progression-free survival (PFS), improvement in pain scores and a longer time to deterioration of quality of life (Qol) scores, investigators reported.

SAN ANTONIO – For premenopausal women with advanced hormone receptor–positive, HER2-negative breast cancer, the addition of the CDK4/6 inhibitor ribociclib (Kisqali) to endocrine therapy and goserelin was associated with a near doubling in progression-free survival (PFS), improvement in pain scores and a longer time to deterioration of quality of life (Qol) scores, investigators reported.

SAN ANTONIO – For premenopausal women with advanced hormone receptor–positive, HER2-negative breast cancer, the addition of the CDK4/6 inhibitor ribociclib (Kisqali) to endocrine therapy and goserelin was associated with a near doubling in progression-free survival (PFS), improvement in pain scores and a longer time to deterioration of quality of life (Qol) scores, investigators reported.