Key clinical point: Colorectal cancer (CRC) screening before 50 years of age was associated with a reduced risk for CRC among US women, including CRC diagnosis before 55 years of age.

Major finding: Compared with no endoscopy, initiating endoscopy at the age of <45 (adjusted hazard ratio [aHR] 0.37; 95% CI 0.26-0.53), 45-49 (aHR 0.43; 95% CI 0.29-0.62), 50-54 (aHR 0.47; 95% CI 0.35-0.62), and ≥55 (aHR 0.46; 95% CI 0.30-0.69) years was associated with a significantly lower CRC risk, with initiating endoscopy before 50 years of age being associated with a decreased risk for CRC diagnosis before 55 years of age (<45 years: aHR 0.45, 95% CI 0.29-0.70; 45-49 years: aHR 0.43, 95% CI, 0.24-0.76).

Study details: This prospective cohort study enrolled 111,801 female health professionals aged 26-46 years with no history of cancer from the Nurses’ Health Study II.

Disclosures: The study was supported by the US National Institutes of Health (NIH). Some authors reported serving as consultants for or receiving research grants or personal fees from various organizations, including NIH.

Source: Ma W et al. Age at initiation of lower gastrointestinal endoscopy and colorectal cancer risk among US women. JAMA Oncol. 2022 (May 5). Doi: 10.1001/jamaoncol.2022.0883

Key clinical point: Colorectal cancer (CRC) screening before 50 years of age was associated with a reduced risk for CRC among US women, including CRC diagnosis before 55 years of age.

Major finding: Compared with no endoscopy, initiating endoscopy at the age of <45 (adjusted hazard ratio [aHR] 0.37; 95% CI 0.26-0.53), 45-49 (aHR 0.43; 95% CI 0.29-0.62), 50-54 (aHR 0.47; 95% CI 0.35-0.62), and ≥55 (aHR 0.46; 95% CI 0.30-0.69) years was associated with a significantly lower CRC risk, with initiating endoscopy before 50 years of age being associated with a decreased risk for CRC diagnosis before 55 years of age (<45 years: aHR 0.45, 95% CI 0.29-0.70; 45-49 years: aHR 0.43, 95% CI, 0.24-0.76).

Study details: This prospective cohort study enrolled 111,801 female health professionals aged 26-46 years with no history of cancer from the Nurses’ Health Study II.

Disclosures: The study was supported by the US National Institutes of Health (NIH). Some authors reported serving as consultants for or receiving research grants or personal fees from various organizations, including NIH.

Source: Ma W et al. Age at initiation of lower gastrointestinal endoscopy and colorectal cancer risk among US women. JAMA Oncol. 2022 (May 5). Doi: 10.1001/jamaoncol.2022.0883

Key clinical point: Colorectal cancer (CRC) screening before 50 years of age was associated with a reduced risk for CRC among US women, including CRC diagnosis before 55 years of age.

Major finding: Compared with no endoscopy, initiating endoscopy at the age of <45 (adjusted hazard ratio [aHR] 0.37; 95% CI 0.26-0.53), 45-49 (aHR 0.43; 95% CI 0.29-0.62), 50-54 (aHR 0.47; 95% CI 0.35-0.62), and ≥55 (aHR 0.46; 95% CI 0.30-0.69) years was associated with a significantly lower CRC risk, with initiating endoscopy before 50 years of age being associated with a decreased risk for CRC diagnosis before 55 years of age (<45 years: aHR 0.45, 95% CI 0.29-0.70; 45-49 years: aHR 0.43, 95% CI, 0.24-0.76).

Study details: This prospective cohort study enrolled 111,801 female health professionals aged 26-46 years with no history of cancer from the Nurses’ Health Study II.

Disclosures: The study was supported by the US National Institutes of Health (NIH). Some authors reported serving as consultants for or receiving research grants or personal fees from various organizations, including NIH.

Source: Ma W et al. Age at initiation of lower gastrointestinal endoscopy and colorectal cancer risk among US women. JAMA Oncol. 2022 (May 5). Doi: 10.1001/jamaoncol.2022.0883

Key clinical point: The proximal serrated polyp (PSP) detection rate (DR) of an endoscopist is inversely associated with the incidence of interval post-colonoscopy colorectal cancer (CRC) and should be universally adopted as a separate quality indicator alongside adenoma DR (ADR) to accelerate CRC prevention.

Major finding: With each percentage point increase in PSP DR, the adjusted interval post-colonoscopy CRC rate reduced by 7% (adjusted hazard ratio 0.93; P < .0001).

Study details: This was a population-based study including patients aged 55-76 years with a positive fecal immunochemical test who underwent a colonoscopy; the data of 277,555 colonoscopies were included in the PSP DR calculations.

Disclosures: The study did not receive any funding. A few authors declared serving as speakers or advisory board members or receiving consulting fees or research grants from various sources.

Source: van Toledo DEFWM et al. Serrated polyp detection and risk of interval post-colonoscopy colorectal cancer: a population-based study. Lancet Gastroenterol Hepatol. 2022 (May 9). Doi: 10.1016/S2468-1253(22)00090-5

Key clinical point: The proximal serrated polyp (PSP) detection rate (DR) of an endoscopist is inversely associated with the incidence of interval post-colonoscopy colorectal cancer (CRC) and should be universally adopted as a separate quality indicator alongside adenoma DR (ADR) to accelerate CRC prevention.

Major finding: With each percentage point increase in PSP DR, the adjusted interval post-colonoscopy CRC rate reduced by 7% (adjusted hazard ratio 0.93; P < .0001).

Study details: This was a population-based study including patients aged 55-76 years with a positive fecal immunochemical test who underwent a colonoscopy; the data of 277,555 colonoscopies were included in the PSP DR calculations.

Disclosures: The study did not receive any funding. A few authors declared serving as speakers or advisory board members or receiving consulting fees or research grants from various sources.

Source: van Toledo DEFWM et al. Serrated polyp detection and risk of interval post-colonoscopy colorectal cancer: a population-based study. Lancet Gastroenterol Hepatol. 2022 (May 9). Doi: 10.1016/S2468-1253(22)00090-5

Key clinical point: The proximal serrated polyp (PSP) detection rate (DR) of an endoscopist is inversely associated with the incidence of interval post-colonoscopy colorectal cancer (CRC) and should be universally adopted as a separate quality indicator alongside adenoma DR (ADR) to accelerate CRC prevention.

Major finding: With each percentage point increase in PSP DR, the adjusted interval post-colonoscopy CRC rate reduced by 7% (adjusted hazard ratio 0.93; P < .0001).

Study details: This was a population-based study including patients aged 55-76 years with a positive fecal immunochemical test who underwent a colonoscopy; the data of 277,555 colonoscopies were included in the PSP DR calculations.

Disclosures: The study did not receive any funding. A few authors declared serving as speakers or advisory board members or receiving consulting fees or research grants from various sources.

Source: van Toledo DEFWM et al. Serrated polyp detection and risk of interval post-colonoscopy colorectal cancer: a population-based study. Lancet Gastroenterol Hepatol. 2022 (May 9). Doi: 10.1016/S2468-1253(22)00090-5

Key clinical point: The proximal serrated polyp (PSP) detection rate (DR) of an endoscopist is inversely associated with the incidence of interval post-colonoscopy colorectal cancer (CRC) and should be universally adopted as a separate quality indicator alongside adenoma DR (ADR) to accelerate CRC prevention.

Major finding: With each percentage point increase in PSP DR, the adjusted interval post-colonoscopy CRC rate reduced by 7% (adjusted hazard ratio 0.93; P < .0001).

Study details: This was a population-based study including patients aged 55-76 years with a positive fecal immunochemical test who underwent a colonoscopy; the data of 277,555 colonoscopies were included in the PSP DR calculations.

Disclosures: The study did not receive any funding. A few authors declared serving as speakers or advisory board members or receiving consulting fees or research grants from various sources.

Source: van Toledo DEFWM et al. Serrated polyp detection and risk of interval post-colonoscopy colorectal cancer: a population-based study. Lancet Gastroenterol Hepatol. 2022 (May 9). Doi: 10.1016/S2468-1253(22)00090-5

Key clinical point: The proximal serrated polyp (PSP) detection rate (DR) of an endoscopist is inversely associated with the incidence of interval post-colonoscopy colorectal cancer (CRC) and should be universally adopted as a separate quality indicator alongside adenoma DR (ADR) to accelerate CRC prevention.

Major finding: With each percentage point increase in PSP DR, the adjusted interval post-colonoscopy CRC rate reduced by 7% (adjusted hazard ratio 0.93; P < .0001).

Study details: This was a population-based study including patients aged 55-76 years with a positive fecal immunochemical test who underwent a colonoscopy; the data of 277,555 colonoscopies were included in the PSP DR calculations.

Disclosures: The study did not receive any funding. A few authors declared serving as speakers or advisory board members or receiving consulting fees or research grants from various sources.

Source: van Toledo DEFWM et al. Serrated polyp detection and risk of interval post-colonoscopy colorectal cancer: a population-based study. Lancet Gastroenterol Hepatol. 2022 (May 9). Doi: 10.1016/S2468-1253(22)00090-5

Key clinical point: The proximal serrated polyp (PSP) detection rate (DR) of an endoscopist is inversely associated with the incidence of interval post-colonoscopy colorectal cancer (CRC) and should be universally adopted as a separate quality indicator alongside adenoma DR (ADR) to accelerate CRC prevention.

Major finding: With each percentage point increase in PSP DR, the adjusted interval post-colonoscopy CRC rate reduced by 7% (adjusted hazard ratio 0.93; P < .0001).

Study details: This was a population-based study including patients aged 55-76 years with a positive fecal immunochemical test who underwent a colonoscopy; the data of 277,555 colonoscopies were included in the PSP DR calculations.

Disclosures: The study did not receive any funding. A few authors declared serving as speakers or advisory board members or receiving consulting fees or research grants from various sources.

Source: van Toledo DEFWM et al. Serrated polyp detection and risk of interval post-colonoscopy colorectal cancer: a population-based study. Lancet Gastroenterol Hepatol. 2022 (May 9). Doi: 10.1016/S2468-1253(22)00090-5

Key clinical point: Patients with synchronous (s) vs metachronous (m) onset of colorectal peritoneal metastasis (PM) had poor overall survival (OS) after cytoreductive surgery (CRS) combined with intraoperative hyperthermic intraperitoneal chemotherapy (HIPEC); however, s-PM was not an independent predictor of OS.

Major finding: Patients with s-PM vs m-PM had a significantly shorter median OS (28 vs 33 months; P = .045). However, rather than the onset of PM (P = .193), factors such as poor differentiation of the primary tumor (adjusted hazard ratio [aHR] 1.95; P = .001), N stage (aHR 1.76; P = .020), and peritoneal cancer index (aHR 1.07; P < .001) independently predicted OS.

Study details: Findings are from a retrospective study including 390 patients who underwent complete CRS-HIPEC for colorectal s-PM (diagnosed during presentation/staging/primary surgery; n = 179) or m-PM (diagnosed during follow-up; n = 211).

Disclosures: No source of funding was reported. the authors declared no conflicts of interest.

source: dietz mv et al. survival outcomes after cytoreductive surgery with hyperthermic intraperitoneal chemotherapy in patients with synchronous versus metachronous onset of peritoneal metastases of colorectal carcinoma. Ann Surg Oncol. 2022 (May 5). Doi: 10.1245/s10434-022-11805-9

Key clinical point: Patients with synchronous (s) vs metachronous (m) onset of colorectal peritoneal metastasis (PM) had poor overall survival (OS) after cytoreductive surgery (CRS) combined with intraoperative hyperthermic intraperitoneal chemotherapy (HIPEC); however, s-PM was not an independent predictor of OS.

Major finding: Patients with s-PM vs m-PM had a significantly shorter median OS (28 vs 33 months; P = .045). However, rather than the onset of PM (P = .193), factors such as poor differentiation of the primary tumor (adjusted hazard ratio [aHR] 1.95; P = .001), N stage (aHR 1.76; P = .020), and peritoneal cancer index (aHR 1.07; P < .001) independently predicted OS.

Study details: Findings are from a retrospective study including 390 patients who underwent complete CRS-HIPEC for colorectal s-PM (diagnosed during presentation/staging/primary surgery; n = 179) or m-PM (diagnosed during follow-up; n = 211).

Disclosures: No source of funding was reported. the authors declared no conflicts of interest.

source: dietz mv et al. survival outcomes after cytoreductive surgery with hyperthermic intraperitoneal chemotherapy in patients with synchronous versus metachronous onset of peritoneal metastases of colorectal carcinoma. Ann Surg Oncol. 2022 (May 5). Doi: 10.1245/s10434-022-11805-9

Key clinical point: Patients with synchronous (s) vs metachronous (m) onset of colorectal peritoneal metastasis (PM) had poor overall survival (OS) after cytoreductive surgery (CRS) combined with intraoperative hyperthermic intraperitoneal chemotherapy (HIPEC); however, s-PM was not an independent predictor of OS.

Major finding: Patients with s-PM vs m-PM had a significantly shorter median OS (28 vs 33 months; P = .045). However, rather than the onset of PM (P = .193), factors such as poor differentiation of the primary tumor (adjusted hazard ratio [aHR] 1.95; P = .001), N stage (aHR 1.76; P = .020), and peritoneal cancer index (aHR 1.07; P < .001) independently predicted OS.

Study details: Findings are from a retrospective study including 390 patients who underwent complete CRS-HIPEC for colorectal s-PM (diagnosed during presentation/staging/primary surgery; n = 179) or m-PM (diagnosed during follow-up; n = 211).

Disclosures: No source of funding was reported. the authors declared no conflicts of interest.

source: dietz mv et al. survival outcomes after cytoreductive surgery with hyperthermic intraperitoneal chemotherapy in patients with synchronous versus metachronous onset of peritoneal metastases of colorectal carcinoma. Ann Surg Oncol. 2022 (May 5). Doi: 10.1245/s10434-022-11805-9

Key clinical point: Coadministration of proton pump inhibitors (PPI) may decrease the effectiveness of capecitabine monotherapy and worsen survival outcomes in patients with stage II-III colorectal cancer (CRC); however, this negative impact may be counteracted with capecitabine plus oxaliplatin (CapeOX).

Major finding: The concomitant use vs nonuse of PPI with capecitabine monotherapy led to shorter relapse-free survival (RFS; adjusted hazard ratio [aHR] 2.48; P = .013) and overall survival (OS; aHR 2.58; P = .052). However, use vs nonuse of PPI with CapeOX had no significant effect on RFS (aHR 0.82; P = .658) or OS (aHR 0.73; P = .621).

Study details: This was a retrospective study including 606 patients aged ≥20 years with stage II-III CRC, of which 54 patients received PPI with ≥1 dose of capecitabine monotherapy (n = 29) or CapeOX (n = 25).

Disclosures: The study was supported by the Keio Gijuku Fukuzawa Memorial Fund for the Advancement of Education and Research in Japan. R Uozumi declared receiving personal fees from a few sources. The other authors declared no conflicts of interest.

Source: Kitazume Y et al. Proton pump inhibitors affect capecitabine efficacy in patients with stage II–III colorectal cancer: A multicenter retrospective study. Sci Rep. 2022;12:6561 (Apr 21). Doi: 10.1038/s41598-022-10008-2

Key clinical point: Coadministration of proton pump inhibitors (PPI) may decrease the effectiveness of capecitabine monotherapy and worsen survival outcomes in patients with stage II-III colorectal cancer (CRC); however, this negative impact may be counteracted with capecitabine plus oxaliplatin (CapeOX).

Major finding: The concomitant use vs nonuse of PPI with capecitabine monotherapy led to shorter relapse-free survival (RFS; adjusted hazard ratio [aHR] 2.48; P = .013) and overall survival (OS; aHR 2.58; P = .052). However, use vs nonuse of PPI with CapeOX had no significant effect on RFS (aHR 0.82; P = .658) or OS (aHR 0.73; P = .621).

Study details: This was a retrospective study including 606 patients aged ≥20 years with stage II-III CRC, of which 54 patients received PPI with ≥1 dose of capecitabine monotherapy (n = 29) or CapeOX (n = 25).

Disclosures: The study was supported by the Keio Gijuku Fukuzawa Memorial Fund for the Advancement of Education and Research in Japan. R Uozumi declared receiving personal fees from a few sources. The other authors declared no conflicts of interest.

Source: Kitazume Y et al. Proton pump inhibitors affect capecitabine efficacy in patients with stage II–III colorectal cancer: A multicenter retrospective study. Sci Rep. 2022;12:6561 (Apr 21). Doi: 10.1038/s41598-022-10008-2

Key clinical point: Coadministration of proton pump inhibitors (PPI) may decrease the effectiveness of capecitabine monotherapy and worsen survival outcomes in patients with stage II-III colorectal cancer (CRC); however, this negative impact may be counteracted with capecitabine plus oxaliplatin (CapeOX).

Major finding: The concomitant use vs nonuse of PPI with capecitabine monotherapy led to shorter relapse-free survival (RFS; adjusted hazard ratio [aHR] 2.48; P = .013) and overall survival (OS; aHR 2.58; P = .052). However, use vs nonuse of PPI with CapeOX had no significant effect on RFS (aHR 0.82; P = .658) or OS (aHR 0.73; P = .621).

Study details: This was a retrospective study including 606 patients aged ≥20 years with stage II-III CRC, of which 54 patients received PPI with ≥1 dose of capecitabine monotherapy (n = 29) or CapeOX (n = 25).

Disclosures: The study was supported by the Keio Gijuku Fukuzawa Memorial Fund for the Advancement of Education and Research in Japan. R Uozumi declared receiving personal fees from a few sources. The other authors declared no conflicts of interest.

Source: Kitazume Y et al. Proton pump inhibitors affect capecitabine efficacy in patients with stage II–III colorectal cancer: A multicenter retrospective study. Sci Rep. 2022;12:6561 (Apr 21). Doi: 10.1038/s41598-022-10008-2

Key clinical point: Coadministration of proton pump inhibitors (PPI) may decrease the effectiveness of capecitabine monotherapy and worsen survival outcomes in patients with stage II-III colorectal cancer (CRC); however, this negative impact may be counteracted with capecitabine plus oxaliplatin (CapeOX).

Major finding: The concomitant use vs nonuse of PPI with capecitabine monotherapy led to shorter relapse-free survival (RFS; adjusted hazard ratio [aHR] 2.48; P = .013) and overall survival (OS; aHR 2.58; P = .052). However, use vs nonuse of PPI with CapeOX had no significant effect on RFS (aHR 0.82; P = .658) or OS (aHR 0.73; P = .621).

Study details: This was a retrospective study including 606 patients aged ≥20 years with stage II-III CRC, of which 54 patients received PPI with ≥1 dose of capecitabine monotherapy (n = 29) or CapeOX (n = 25).

Disclosures: The study was supported by the Keio Gijuku Fukuzawa Memorial Fund for the Advancement of Education and Research in Japan. R Uozumi declared receiving personal fees from a few sources. The other authors declared no conflicts of interest.

Source: Kitazume Y et al. Proton pump inhibitors affect capecitabine efficacy in patients with stage II–III colorectal cancer: A multicenter retrospective study. Sci Rep. 2022;12:6561 (Apr 21). Doi: 10.1038/s41598-022-10008-2

Key clinical point: Coadministration of proton pump inhibitors (PPI) may decrease the effectiveness of capecitabine monotherapy and worsen survival outcomes in patients with stage II-III colorectal cancer (CRC); however, this negative impact may be counteracted with capecitabine plus oxaliplatin (CapeOX).

Major finding: The concomitant use vs nonuse of PPI with capecitabine monotherapy led to shorter relapse-free survival (RFS; adjusted hazard ratio [aHR] 2.48; P = .013) and overall survival (OS; aHR 2.58; P = .052). However, use vs nonuse of PPI with CapeOX had no significant effect on RFS (aHR 0.82; P = .658) or OS (aHR 0.73; P = .621).

Study details: This was a retrospective study including 606 patients aged ≥20 years with stage II-III CRC, of which 54 patients received PPI with ≥1 dose of capecitabine monotherapy (n = 29) or CapeOX (n = 25).

Disclosures: The study was supported by the Keio Gijuku Fukuzawa Memorial Fund for the Advancement of Education and Research in Japan. R Uozumi declared receiving personal fees from a few sources. The other authors declared no conflicts of interest.

Source: Kitazume Y et al. Proton pump inhibitors affect capecitabine efficacy in patients with stage II–III colorectal cancer: A multicenter retrospective study. Sci Rep. 2022;12:6561 (Apr 21). Doi: 10.1038/s41598-022-10008-2

Key clinical point: Coadministration of proton pump inhibitors (PPI) may decrease the effectiveness of capecitabine monotherapy and worsen survival outcomes in patients with stage II-III colorectal cancer (CRC); however, this negative impact may be counteracted with capecitabine plus oxaliplatin (CapeOX).

Major finding: The concomitant use vs nonuse of PPI with capecitabine monotherapy led to shorter relapse-free survival (RFS; adjusted hazard ratio [aHR] 2.48; P = .013) and overall survival (OS; aHR 2.58; P = .052). However, use vs nonuse of PPI with CapeOX had no significant effect on RFS (aHR 0.82; P = .658) or OS (aHR 0.73; P = .621).

Study details: This was a retrospective study including 606 patients aged ≥20 years with stage II-III CRC, of which 54 patients received PPI with ≥1 dose of capecitabine monotherapy (n = 29) or CapeOX (n = 25).

Disclosures: The study was supported by the Keio Gijuku Fukuzawa Memorial Fund for the Advancement of Education and Research in Japan. R Uozumi declared receiving personal fees from a few sources. The other authors declared no conflicts of interest.

Source: Kitazume Y et al. Proton pump inhibitors affect capecitabine efficacy in patients with stage II–III colorectal cancer: A multicenter retrospective study. Sci Rep. 2022;12:6561 (Apr 21). Doi: 10.1038/s41598-022-10008-2

Key clinical point: Trifluridine/tipiracil plus bevacizumab (TT-B) appears to be a promising first-line therapeutic regimen for patients with unresectable metastatic colorectal cancer (mCRC) who are ineligible for intensive chemotherapy.

Major finding: The median overall survival (OS) with TT-B (22.3 months) vs capecitabine plus bevacizumab (C-B; 17.7 months) was longer by 4.6 months (adjusted hazard ratio 0.78; 95% CI 0.55-1.10). No new safety signals were observed.

Study details: The data are the final OS results of the phase 2 TASCO1 study that included 153 adult patients with unresectable mCRC who were randomly assigned to receive first-line TT-B (n = 77) or C-B (n = 76), with cycles repeated every 4 or 3 weeks, respectively.

Disclosures: The study was sponsored by Servier and Taiho. Some authors declared serving as advisory board members or meeting chairs of, or receiving research grants and travel and accommodation expenses from various organizations, including Servier and Taiho. The other authors are employees of Servier.

Source: Van Cutsem E et al. First-line trifluridine/tipiracil + bevacizumab in patients with unresectable metastatic colorectal cancer: Final survival analysis in the TASCO1 study. Br J Cancer. 2022;126:1548-1554 (Apr 19). Doi: 10.1038/s41416-022-01737-2

Key clinical point: Trifluridine/tipiracil plus bevacizumab (TT-B) appears to be a promising first-line therapeutic regimen for patients with unresectable metastatic colorectal cancer (mCRC) who are ineligible for intensive chemotherapy.

Major finding: The median overall survival (OS) with TT-B (22.3 months) vs capecitabine plus bevacizumab (C-B; 17.7 months) was longer by 4.6 months (adjusted hazard ratio 0.78; 95% CI 0.55-1.10). No new safety signals were observed.

Study details: The data are the final OS results of the phase 2 TASCO1 study that included 153 adult patients with unresectable mCRC who were randomly assigned to receive first-line TT-B (n = 77) or C-B (n = 76), with cycles repeated every 4 or 3 weeks, respectively.

Disclosures: The study was sponsored by Servier and Taiho. Some authors declared serving as advisory board members or meeting chairs of, or receiving research grants and travel and accommodation expenses from various organizations, including Servier and Taiho. The other authors are employees of Servier.

Source: Van Cutsem E et al. First-line trifluridine/tipiracil + bevacizumab in patients with unresectable metastatic colorectal cancer: Final survival analysis in the TASCO1 study. Br J Cancer. 2022;126:1548-1554 (Apr 19). Doi: 10.1038/s41416-022-01737-2

Key clinical point: Trifluridine/tipiracil plus bevacizumab (TT-B) appears to be a promising first-line therapeutic regimen for patients with unresectable metastatic colorectal cancer (mCRC) who are ineligible for intensive chemotherapy.

Major finding: The median overall survival (OS) with TT-B (22.3 months) vs capecitabine plus bevacizumab (C-B; 17.7 months) was longer by 4.6 months (adjusted hazard ratio 0.78; 95% CI 0.55-1.10). No new safety signals were observed.

Study details: The data are the final OS results of the phase 2 TASCO1 study that included 153 adult patients with unresectable mCRC who were randomly assigned to receive first-line TT-B (n = 77) or C-B (n = 76), with cycles repeated every 4 or 3 weeks, respectively.

Disclosures: The study was sponsored by Servier and Taiho. Some authors declared serving as advisory board members or meeting chairs of, or receiving research grants and travel and accommodation expenses from various organizations, including Servier and Taiho. The other authors are employees of Servier.

Source: Van Cutsem E et al. First-line trifluridine/tipiracil + bevacizumab in patients with unresectable metastatic colorectal cancer: Final survival analysis in the TASCO1 study. Br J Cancer. 2022;126:1548-1554 (Apr 19). Doi: 10.1038/s41416-022-01737-2

Key clinical point: In an updated KEYNOTE-177 analysis, first-line pembrolizumab vs chemotherapy did not improve survival in patients with microsatellite instability-high (MSI-H) or mismatch repair-deficient (dMMR) metastatic colorectal cancer (mCRC), but improved progression-free survival (PFS) and led to fewer treatment-related adverse events (TAE).

Major finding: Pembrolizumab vs chemotherapy provided no survival benefit as the one-sided α boundary for superiority (0.025) was not met (hazard ratio [HR] 0.74; P = .036). However, it prolonged median PFS (16.5 vs 8.2 months; HR 0.59; 95% CI 0.45-0.79) and lowered the grade ≥3 TAE rate (22% vs 66%).

Study details: These are the final analysis data from the phase 3 KEYNOTE-177 trial that included 307 adult patients with previously untreated MSI-H or dMMR mCRC who were randomly assigned to receive pembrolizumab or chemotherapy.

Disclosures: Merck Sharp & Dohme (MSD; Merck subsidiary) sponsored the study. Some authors reported serving on the directorial board of, receiving institutional or clinical trial funding, advisory or consultant honoraria, or travel or accommodation expenses from various sources, including MSD. The other authors are MSD employees and Merck shareholders.

Source: Diaz LA Jr et al. Pembrolizumab versus chemotherapy for microsatellite instability-high or mismatch repair-deficient metastatic colorectal cancer (KEYNOTE-177): Final analysis of a randomised, open-label, phase 3 study. Lancet Oncol. 2022;23(5):659-670 (Apr 12). Doi: 10.1016/S1470-2045(22)00197-8

Key clinical point: In an updated KEYNOTE-177 analysis, first-line pembrolizumab vs chemotherapy did not improve survival in patients with microsatellite instability-high (MSI-H) or mismatch repair-deficient (dMMR) metastatic colorectal cancer (mCRC), but improved progression-free survival (PFS) and led to fewer treatment-related adverse events (TAE).

Major finding: Pembrolizumab vs chemotherapy provided no survival benefit as the one-sided α boundary for superiority (0.025) was not met (hazard ratio [HR] 0.74; P = .036). However, it prolonged median PFS (16.5 vs 8.2 months; HR 0.59; 95% CI 0.45-0.79) and lowered the grade ≥3 TAE rate (22% vs 66%).

Study details: These are the final analysis data from the phase 3 KEYNOTE-177 trial that included 307 adult patients with previously untreated MSI-H or dMMR mCRC who were randomly assigned to receive pembrolizumab or chemotherapy.

Disclosures: Merck Sharp & Dohme (MSD; Merck subsidiary) sponsored the study. Some authors reported serving on the directorial board of, receiving institutional or clinical trial funding, advisory or consultant honoraria, or travel or accommodation expenses from various sources, including MSD. The other authors are MSD employees and Merck shareholders.

Source: Diaz LA Jr et al. Pembrolizumab versus chemotherapy for microsatellite instability-high or mismatch repair-deficient metastatic colorectal cancer (KEYNOTE-177): Final analysis of a randomised, open-label, phase 3 study. Lancet Oncol. 2022;23(5):659-670 (Apr 12). Doi: 10.1016/S1470-2045(22)00197-8

Key clinical point: In an updated KEYNOTE-177 analysis, first-line pembrolizumab vs chemotherapy did not improve survival in patients with microsatellite instability-high (MSI-H) or mismatch repair-deficient (dMMR) metastatic colorectal cancer (mCRC), but improved progression-free survival (PFS) and led to fewer treatment-related adverse events (TAE).

Major finding: Pembrolizumab vs chemotherapy provided no survival benefit as the one-sided α boundary for superiority (0.025) was not met (hazard ratio [HR] 0.74; P = .036). However, it prolonged median PFS (16.5 vs 8.2 months; HR 0.59; 95% CI 0.45-0.79) and lowered the grade ≥3 TAE rate (22% vs 66%).

Study details: These are the final analysis data from the phase 3 KEYNOTE-177 trial that included 307 adult patients with previously untreated MSI-H or dMMR mCRC who were randomly assigned to receive pembrolizumab or chemotherapy.

Disclosures: Merck Sharp & Dohme (MSD; Merck subsidiary) sponsored the study. Some authors reported serving on the directorial board of, receiving institutional or clinical trial funding, advisory or consultant honoraria, or travel or accommodation expenses from various sources, including MSD. The other authors are MSD employees and Merck shareholders.

Source: Diaz LA Jr et al. Pembrolizumab versus chemotherapy for microsatellite instability-high or mismatch repair-deficient metastatic colorectal cancer (KEYNOTE-177): Final analysis of a randomised, open-label, phase 3 study. Lancet Oncol. 2022;23(5):659-670 (Apr 12). Doi: 10.1016/S1470-2045(22)00197-8

Key clinical point: The findings from the C-Cubed study support the extension of sequential treatment (fluoropyrimidines with bevacizumab followed by oxaliplatin at first progression) over combination treatment (fluoropyrimidines and oxaliplatin with bevacizumab) in selected patients with previously untreated metastatic colorectal cancer (mCRC) who do not need an objective response.

Major finding: Sequential vs combination treatment led to a significantly longer time to failure of strategy (15.2 vs 7.8 months; hazard ratio 0.49; P < .0001). However, the median overall survival (P = .61) or time between randomization and the first progressive disease (P = .12) was not significantly different between the treatment groups.

Study details: Findings are from a phase 3 trial, C-Cubed Study, which included 300 patients aged ≥20 years with previously untreated mCRC who were randomly assigned to receive sequential (n = 151) or combination (n = 149) treatment.

Disclosures: The study was sponsored by Chugai Pharmaceutical, Co., Ltd. Some authors reported receiving grants or personal fees from various sources, including Chugai Pharmaceutical.

Source: Inada R et al. Phase 3 trial of sequential versus combination treatment in colorectal cancer: The C-cubed study. Eur J Cancer. 2022;169:166-178 (May 12). Doi: 10.1016/j.ejca.2022.04.009

Key clinical point: The findings from the C-Cubed study support the extension of sequential treatment (fluoropyrimidines with bevacizumab followed by oxaliplatin at first progression) over combination treatment (fluoropyrimidines and oxaliplatin with bevacizumab) in selected patients with previously untreated metastatic colorectal cancer (mCRC) who do not need an objective response.

Major finding: Sequential vs combination treatment led to a significantly longer time to failure of strategy (15.2 vs 7.8 months; hazard ratio 0.49; P < .0001). However, the median overall survival (P = .61) or time between randomization and the first progressive disease (P = .12) was not significantly different between the treatment groups.

Study details: Findings are from a phase 3 trial, C-Cubed Study, which included 300 patients aged ≥20 years with previously untreated mCRC who were randomly assigned to receive sequential (n = 151) or combination (n = 149) treatment.

Disclosures: The study was sponsored by Chugai Pharmaceutical, Co., Ltd. Some authors reported receiving grants or personal fees from various sources, including Chugai Pharmaceutical.

Source: Inada R et al. Phase 3 trial of sequential versus combination treatment in colorectal cancer: The C-cubed study. Eur J Cancer. 2022;169:166-178 (May 12). Doi: 10.1016/j.ejca.2022.04.009

Key clinical point: The findings from the C-Cubed study support the extension of sequential treatment (fluoropyrimidines with bevacizumab followed by oxaliplatin at first progression) over combination treatment (fluoropyrimidines and oxaliplatin with bevacizumab) in selected patients with previously untreated metastatic colorectal cancer (mCRC) who do not need an objective response.

Major finding: Sequential vs combination treatment led to a significantly longer time to failure of strategy (15.2 vs 7.8 months; hazard ratio 0.49; P < .0001). However, the median overall survival (P = .61) or time between randomization and the first progressive disease (P = .12) was not significantly different between the treatment groups.

Study details: Findings are from a phase 3 trial, C-Cubed Study, which included 300 patients aged ≥20 years with previously untreated mCRC who were randomly assigned to receive sequential (n = 151) or combination (n = 149) treatment.

Disclosures: The study was sponsored by Chugai Pharmaceutical, Co., Ltd. Some authors reported receiving grants or personal fees from various sources, including Chugai Pharmaceutical.

Source: Inada R et al. Phase 3 trial of sequential versus combination treatment in colorectal cancer: The C-cubed study. Eur J Cancer. 2022;169:166-178 (May 12). Doi: 10.1016/j.ejca.2022.04.009

Not all patients with chronic obstructive pulmonary disease (COPD) respond equally well to pulmonary rehabilitation (PR).

Now, physicians can better categorize which patients will do well with PR and which ones less well or not well at all based on a new system of clustering of COPD patients according to their response to exercise therapy.

“We identified four clusters of COPD patients and their response to PR in the aim to better understand PR outcome and [adapt] it to patients’ profiles and needs,” lead author Yara Al Chikhanie, MD, of the cardiopulmonary rehabilitation center Dieulefit Sante (France), and colleagues observed.

“Identification of patients likely to show smaller responses to PR may help to target patients benefiting the most and to adapt PR settings for nonresponders to standard PR,” they suggested.

The study was published online in Respiratory Medicine.

Single-center cohort

The cohort consisted of 835 patients from a single center who had been admitted to a cardiopulmonary rehabilitation center over a 6-year period from 2021 to 2017. “The PR program used in the center was the same over the 6-year period,” the authors note – consisting of a 3- to 4-week, inpatient program with activities 5 days a week.

Each day, patients attended a 25-minute aerobic training session on a cycling ergometer or a treadmill; a 30-minute low-intensity gym session; a 30-minute group walk outdoors, and 30 minutes of strength training. “We aimed to cluster patients with COPD admitted to PR based on patients’ clinical characteristics and 6-meter walk test results (6MWT), pulse oxygen saturation (SPO₂), heart rate (HR), and dyspnea,” the authors explained.

They then evaluated patient response to PR in each of these clusters based on the amount of improvement in the 6-meter walk distance (6MWD), lung function, and quality of life observed, they added.

The population consisted of seniors, equally men and women, mostly GOLD II and III patients (a measure of lung function) with a limited walking capacity, some 84% of the cohort having a 6MWD <80% predicted. The characteristics of the four identified clusters were as follows:

• Cluster 1: Consisted of younger men, GOLD I to II, average walkers, obese. The average 6MWD was 430 meters and patients had a large exercise HR response to PR. This cluster had a 76 meter improvement in their 6MWD, although 16% of the same cluster still did not respond to PR.
• Cluster 2: Consisted of older women, GOLD II-III, who were slow walkers. This cluster had a reduced 6MWD of 362 meters, but they also had a significant 97-meter improvement in their 6MWD following PR. Some 18% were still nonresponders to PR.
• Cluster 3: Consisted of older men, GOLD II to III, dyspneic, slow walkers, some 32% of whom responded to PR. This cluster also had a reduced 6MWD at 388 meters, but again, they also had a significant improvement of 79 meters in their 6MWD following the introduction of PR. Some 11% were nonresponders to PR.
• Cluster 4: Consisted of older men, GOLD III to IV, very slow walkers, oxygen-dependent, very dyspneic. This cluster had a severely reduced 6MWD of only 290 meters with severe exercise desaturation and dyspnea, and almost all of them were on long-term oxygen therapy. Nevertheless, this cluster also had a significant, 66-meter improvement in their 6MWD. Twenty-eight percent of them were nonresponders to PR.

Clinical practice

“The highly heterogeneous nature of the enrolled patient population reflects clinical practice,” the authors point out. For example, cluster 1 included patients with the best lung function, compared with those in clusters 2, 3, and 4 – which may be due, at least in part, to the aggravation in disease severity with age given that patients in cluster 1 were the youngest overall.

The fact that those in cluster 4 had the worst performance may also have been because of age and disease severity, the authors note, as those in cluster 4 had the highest proportion of patients on long-term oxygen therapy, again suggestive of disease severity. “Of note, these patients show the most impaired 6MWT responses despite the use of oxygen supplementation during walking,” the researchers added.

The authors also suggest that patients such as those in cluster 4 may require specific PR modalities in order to optimize their functional benefits. In contrast, those in cluster 1 had a significantly higher body mass index, compared with those in the other 3 clusters, which, interestingly enough, was not associated with more severe functional exercise impairment. The fact that older age participants, such as those in cluster 3 as well as those with high BMI in cluster 1, were both able to improve their 6MWD post-PR to the same extent as younger patients without obesity suggests that most older or overweight/obese patients can still show clinically significant improvement in 6MWD post PR, as the authors suggest.

Notably, the 6MWT was the only test available both pre-and post PR, making this an important limitation of the study, because only one aspect of the effect of PR was evaluated, omitting other physical and psychosocial benefits of PR, investigators suggest.

Adds to the literature

Asked to comment on the findings, Sachin Gupta, MD, attending physician, pulmonary & critical care medicine, Alameda Health System, Highland Hospital, Oakland, Calif., felt that these data add to the literature in defining COPD patient profiles, helping to categorize those in whom to expect greater walk distance improvements with PR versus those who will respond less well.

“Because 6MWD is a surrogate marker for quality of life (QOL) and mortality, further analysis in the form of a randomized controlled trial to determine long-term outcomes among the four clusters with adjustment for baseline characteristics would help determine the extent to which certain patient clusters may respond to PR,” Dr. Gupta told this news organization in an email.

At the same time, he suggested that while patients may not experience much net benefit in their 6MWD, their QOL or mortality risk may still improve with PR. “I cannot recall a patient ever describing their experience with PR as anything other than positive,” Dr. Gupta stressed.

“And as the authors [themselves] note, because PR serves to benefit patients beyond the 6MWD, I would not recommend limiting PR referrals based on the patient clusters identified,” he said.

The authors had no conflicts of interest to declare. Dr. Gupta declared that he is an employee and shareholder at Genentech.

Not all patients with chronic obstructive pulmonary disease (COPD) respond equally well to pulmonary rehabilitation (PR).

Now, physicians can better categorize which patients will do well with PR and which ones less well or not well at all based on a new system of clustering of COPD patients according to their response to exercise therapy.

“We identified four clusters of COPD patients and their response to PR in the aim to better understand PR outcome and [adapt] it to patients’ profiles and needs,” lead author Yara Al Chikhanie, MD, of the cardiopulmonary rehabilitation center Dieulefit Sante (France), and colleagues observed.

“Identification of patients likely to show smaller responses to PR may help to target patients benefiting the most and to adapt PR settings for nonresponders to standard PR,” they suggested.

The study was published online in Respiratory Medicine.

Single-center cohort

The cohort consisted of 835 patients from a single center who had been admitted to a cardiopulmonary rehabilitation center over a 6-year period from 2021 to 2017. “The PR program used in the center was the same over the 6-year period,” the authors note – consisting of a 3- to 4-week, inpatient program with activities 5 days a week.

Each day, patients attended a 25-minute aerobic training session on a cycling ergometer or a treadmill; a 30-minute low-intensity gym session; a 30-minute group walk outdoors, and 30 minutes of strength training. “We aimed to cluster patients with COPD admitted to PR based on patients’ clinical characteristics and 6-meter walk test results (6MWT), pulse oxygen saturation (SPO₂), heart rate (HR), and dyspnea,” the authors explained.

They then evaluated patient response to PR in each of these clusters based on the amount of improvement in the 6-meter walk distance (6MWD), lung function, and quality of life observed, they added.

The population consisted of seniors, equally men and women, mostly GOLD II and III patients (a measure of lung function) with a limited walking capacity, some 84% of the cohort having a 6MWD <80% predicted. The characteristics of the four identified clusters were as follows:

• Cluster 1: Consisted of younger men, GOLD I to II, average walkers, obese. The average 6MWD was 430 meters and patients had a large exercise HR response to PR. This cluster had a 76 meter improvement in their 6MWD, although 16% of the same cluster still did not respond to PR.
• Cluster 2: Consisted of older women, GOLD II-III, who were slow walkers. This cluster had a reduced 6MWD of 362 meters, but they also had a significant 97-meter improvement in their 6MWD following PR. Some 18% were still nonresponders to PR.
• Cluster 3: Consisted of older men, GOLD II to III, dyspneic, slow walkers, some 32% of whom responded to PR. This cluster also had a reduced 6MWD at 388 meters, but again, they also had a significant improvement of 79 meters in their 6MWD following the introduction of PR. Some 11% were nonresponders to PR.
• Cluster 4: Consisted of older men, GOLD III to IV, very slow walkers, oxygen-dependent, very dyspneic. This cluster had a severely reduced 6MWD of only 290 meters with severe exercise desaturation and dyspnea, and almost all of them were on long-term oxygen therapy. Nevertheless, this cluster also had a significant, 66-meter improvement in their 6MWD. Twenty-eight percent of them were nonresponders to PR.

Clinical practice

“The highly heterogeneous nature of the enrolled patient population reflects clinical practice,” the authors point out. For example, cluster 1 included patients with the best lung function, compared with those in clusters 2, 3, and 4 – which may be due, at least in part, to the aggravation in disease severity with age given that patients in cluster 1 were the youngest overall.

The fact that those in cluster 4 had the worst performance may also have been because of age and disease severity, the authors note, as those in cluster 4 had the highest proportion of patients on long-term oxygen therapy, again suggestive of disease severity. “Of note, these patients show the most impaired 6MWT responses despite the use of oxygen supplementation during walking,” the researchers added.

The authors also suggest that patients such as those in cluster 4 may require specific PR modalities in order to optimize their functional benefits. In contrast, those in cluster 1 had a significantly higher body mass index, compared with those in the other 3 clusters, which, interestingly enough, was not associated with more severe functional exercise impairment. The fact that older age participants, such as those in cluster 3 as well as those with high BMI in cluster 1, were both able to improve their 6MWD post-PR to the same extent as younger patients without obesity suggests that most older or overweight/obese patients can still show clinically significant improvement in 6MWD post PR, as the authors suggest.

Notably, the 6MWT was the only test available both pre-and post PR, making this an important limitation of the study, because only one aspect of the effect of PR was evaluated, omitting other physical and psychosocial benefits of PR, investigators suggest.

Adds to the literature

Asked to comment on the findings, Sachin Gupta, MD, attending physician, pulmonary & critical care medicine, Alameda Health System, Highland Hospital, Oakland, Calif., felt that these data add to the literature in defining COPD patient profiles, helping to categorize those in whom to expect greater walk distance improvements with PR versus those who will respond less well.

“Because 6MWD is a surrogate marker for quality of life (QOL) and mortality, further analysis in the form of a randomized controlled trial to determine long-term outcomes among the four clusters with adjustment for baseline characteristics would help determine the extent to which certain patient clusters may respond to PR,” Dr. Gupta told this news organization in an email.

At the same time, he suggested that while patients may not experience much net benefit in their 6MWD, their QOL or mortality risk may still improve with PR. “I cannot recall a patient ever describing their experience with PR as anything other than positive,” Dr. Gupta stressed.

“And as the authors [themselves] note, because PR serves to benefit patients beyond the 6MWD, I would not recommend limiting PR referrals based on the patient clusters identified,” he said.

The authors had no conflicts of interest to declare. Dr. Gupta declared that he is an employee and shareholder at Genentech.

Not all patients with chronic obstructive pulmonary disease (COPD) respond equally well to pulmonary rehabilitation (PR).

Now, physicians can better categorize which patients will do well with PR and which ones less well or not well at all based on a new system of clustering of COPD patients according to their response to exercise therapy.

“We identified four clusters of COPD patients and their response to PR in the aim to better understand PR outcome and [adapt] it to patients’ profiles and needs,” lead author Yara Al Chikhanie, MD, of the cardiopulmonary rehabilitation center Dieulefit Sante (France), and colleagues observed.

“Identification of patients likely to show smaller responses to PR may help to target patients benefiting the most and to adapt PR settings for nonresponders to standard PR,” they suggested.

The study was published online in Respiratory Medicine.

Single-center cohort

The cohort consisted of 835 patients from a single center who had been admitted to a cardiopulmonary rehabilitation center over a 6-year period from 2021 to 2017. “The PR program used in the center was the same over the 6-year period,” the authors note – consisting of a 3- to 4-week, inpatient program with activities 5 days a week.

Each day, patients attended a 25-minute aerobic training session on a cycling ergometer or a treadmill; a 30-minute low-intensity gym session; a 30-minute group walk outdoors, and 30 minutes of strength training. “We aimed to cluster patients with COPD admitted to PR based on patients’ clinical characteristics and 6-meter walk test results (6MWT), pulse oxygen saturation (SPO₂), heart rate (HR), and dyspnea,” the authors explained.

They then evaluated patient response to PR in each of these clusters based on the amount of improvement in the 6-meter walk distance (6MWD), lung function, and quality of life observed, they added.

The population consisted of seniors, equally men and women, mostly GOLD II and III patients (a measure of lung function) with a limited walking capacity, some 84% of the cohort having a 6MWD <80% predicted. The characteristics of the four identified clusters were as follows:

• Cluster 1: Consisted of younger men, GOLD I to II, average walkers, obese. The average 6MWD was 430 meters and patients had a large exercise HR response to PR. This cluster had a 76 meter improvement in their 6MWD, although 16% of the same cluster still did not respond to PR.
• Cluster 2: Consisted of older women, GOLD II-III, who were slow walkers. This cluster had a reduced 6MWD of 362 meters, but they also had a significant 97-meter improvement in their 6MWD following PR. Some 18% were still nonresponders to PR.
• Cluster 3: Consisted of older men, GOLD II to III, dyspneic, slow walkers, some 32% of whom responded to PR. This cluster also had a reduced 6MWD at 388 meters, but again, they also had a significant improvement of 79 meters in their 6MWD following the introduction of PR. Some 11% were nonresponders to PR.
• Cluster 4: Consisted of older men, GOLD III to IV, very slow walkers, oxygen-dependent, very dyspneic. This cluster had a severely reduced 6MWD of only 290 meters with severe exercise desaturation and dyspnea, and almost all of them were on long-term oxygen therapy. Nevertheless, this cluster also had a significant, 66-meter improvement in their 6MWD. Twenty-eight percent of them were nonresponders to PR.

Clinical practice

“The highly heterogeneous nature of the enrolled patient population reflects clinical practice,” the authors point out. For example, cluster 1 included patients with the best lung function, compared with those in clusters 2, 3, and 4 – which may be due, at least in part, to the aggravation in disease severity with age given that patients in cluster 1 were the youngest overall.

The fact that those in cluster 4 had the worst performance may also have been because of age and disease severity, the authors note, as those in cluster 4 had the highest proportion of patients on long-term oxygen therapy, again suggestive of disease severity. “Of note, these patients show the most impaired 6MWT responses despite the use of oxygen supplementation during walking,” the researchers added.

The authors also suggest that patients such as those in cluster 4 may require specific PR modalities in order to optimize their functional benefits. In contrast, those in cluster 1 had a significantly higher body mass index, compared with those in the other 3 clusters, which, interestingly enough, was not associated with more severe functional exercise impairment. The fact that older age participants, such as those in cluster 3 as well as those with high BMI in cluster 1, were both able to improve their 6MWD post-PR to the same extent as younger patients without obesity suggests that most older or overweight/obese patients can still show clinically significant improvement in 6MWD post PR, as the authors suggest.

Notably, the 6MWT was the only test available both pre-and post PR, making this an important limitation of the study, because only one aspect of the effect of PR was evaluated, omitting other physical and psychosocial benefits of PR, investigators suggest.

Adds to the literature

Asked to comment on the findings, Sachin Gupta, MD, attending physician, pulmonary & critical care medicine, Alameda Health System, Highland Hospital, Oakland, Calif., felt that these data add to the literature in defining COPD patient profiles, helping to categorize those in whom to expect greater walk distance improvements with PR versus those who will respond less well.

“Because 6MWD is a surrogate marker for quality of life (QOL) and mortality, further analysis in the form of a randomized controlled trial to determine long-term outcomes among the four clusters with adjustment for baseline characteristics would help determine the extent to which certain patient clusters may respond to PR,” Dr. Gupta told this news organization in an email.

At the same time, he suggested that while patients may not experience much net benefit in their 6MWD, their QOL or mortality risk may still improve with PR. “I cannot recall a patient ever describing their experience with PR as anything other than positive,” Dr. Gupta stressed.

“And as the authors [themselves] note, because PR serves to benefit patients beyond the 6MWD, I would not recommend limiting PR referrals based on the patient clusters identified,” he said.

The authors had no conflicts of interest to declare. Dr. Gupta declared that he is an employee and shareholder at Genentech.