January 22, 2021
2 min read
Shiu KK, et al. Abstract 6. Presented at: Gastrointestinal Cancers Symposium (virtual meeting); Jan. 15-17, 2021.
Merck Sharp & Dohme funded this study. Shiu reports consultant/advisory roles with Merck Sharp & Dohme and Roche; honoraria from Bristol Myers Squibb, Guardant Health, Innovent Biologics, Merck, Merck Sharp & Dohme, Roche and Servier; research funding from Bristol Myers Squibb, Gilead Sciences, Merck, Merck Sharp & Dohme and Roche; and travel expenses from Innovent Biologics, Merck Sharp & Dohme, Roche and Servier. Please see the abstract for all other researchers’ relevant financial disclosures.
Pembrolizumab monotherapy demonstrated superior PFS and PFS2 compared with standard-of-care chemotherapy among patients with microsatellite-instability high/mismatch repair-deficient metastatic colorectal cancer.
Pembrolizumab (Keytruda, Merck), an anti-PD-1 antibody, also had an acceptable safety profile, with fewer treatment-associated adverse events than chemotherapy, according to results of the phase KEYNOTE-177 trial presented at Gastrointestinal Cancers Symposium.
“We know that microsatellite instability is detected in only around 5% of patients with advanced colon cancer,” Kai-Keen Shiu, MD, gastrointestinal medical oncologist at University College Hospital of NHS Foundation Trust in London, said during his presentation. “However, pembrolizumab has shown clinical benefit in patients pretreated with chemotherapy in the advanced setting. We also presented data at the [ASCO20 Virtual Scientific Program] on improvements in PFS with pembrolizumab vs. chemotherapy as first-line treatment in the KEYNOTE-177 trial.”
KEYNOTE-177 analyzed pembrolizumab vs. chemotherapy plus bevacizumab (Avastin, Genentech) or cetuximab (Erbitux, Eli Lilly) as first-line treatment for patients with microsatellite-instability high/mismatch repair deficient metastatic colorectal cancer and ECOG performance status of 0 or 1.
Shiu and colleagues randomly assigned 307 patients to either 200 mg pembrolizumab every 3 weeks for up to 2 years (n = 153; median age, 63 years; 54% women) or investigator’s choice of one of six standard chemotherapy regimens selected prior to randomization (n = 154; median age, 62.5 years; 53% men). Chemotherapy regimens included modified FOLFOX-6, which consists of 5-FU, leucovorin and oxaliplatin; modified FOLFOX-6 plus bevacizumab; modified FOLFOX-6 plus cetuximab; FOLFIRI, which consists of leucovorin, 5-FU and irinotecan; FOLFIRI plus bevacizumab; or FOLFIRI plus cetuximab.
Patients in the pembrolizumab group continued treatment for 35 cycles or until progression, unacceptable toxicity or study withdrawal. Those in the chemotherapy group could cross over to pembrolizumab for as many as 35 cycles after confirmed progression.
PFS and OS served as primary endpoints. Key secondary endpoints included overall response rate and safety. Researchers also assessed duration of response, health-related quality of life and PFS2, defined as the time from randomization to progression on the next line of therapy or death of any cause.
Median follow-up was 32.4 months.
Healio previously reported that pembrolizumab conferred longer median PFS than chemotherapy (16.5 months vs. 8.2 months; HR = 0.6; 95% CI, 0.45-0.8), as well as higher rates of PFS at 1 year (55.3% vs. 37.3%) and at 2 years (48.3% vs. 18.6%).
During the symposium, Shiu also reported longer median PFS2 with pembrolizumab vs. chemotherapy (not yet reached vs. 23.5 months; HR = 0.63; 95% CI, 0.45-0.88).
Confirmed ORRs were 43.8% with pembrolizumab vs. 33.1% with chemotherapy.
“Of note, there was slightly better stabilization of disease with chemotherapy and more patients progressed on pembrolizumab,” Shiu said.
However, median duration of response was not yet reached with pembrolizumab vs. 10.6 months with chemotherapy.
“Fifty-six patients assigned chemotherapy [36%] crossed over to pembrolizumab and 35 additional patients received anti-PD-1/PD-L1 therapy outside of the study, for an effective crossover rate of 59% in the intention-to-treat population,” Shiu said. “Final OS analysis is ongoing.”
Grade 3 treatment-related adverse events occurred among 22% assigned pembrolizumab and 66% of those assigned chemotherapy. One patient in the chemotherapy group experienced grade 5 intestinal perforation, but no grade 5 events occurred with pembrolizumab.
Researchers also observed improvements in health-related quality of life scores with pembrolizumab vs. chemotherapy, according to Shiu.
“Many patients could continue working or function extremely well when on pembrolizumab compared with chemotherapy, and patients who previously had adjuvant chemotherapy reported that pembrolizumab was better tolerated for them,” Shiu said. “These data support pembrolizumab as a new standard of care for patients with microsatellite-instability high/mismatch repair-deficient metastatic colorectal cancer. We keenly await OS data and look forward to upcoming studies in the neoadjuvant and adjuvant setting.”