The median PFS was 16.5 months for patients who received pembrolizumab and 8.2 months for those who received investigators’ choice of chemotherapy (one of six regimens).
“In the past, no medical treatment has shown such difference in terms of improvement of PFS in metastatic colorectal cancer,” said study investigator, of Hôpital Saint Antoine in Paris.
“Today, this study demonstrates that the majority of the 5% of patients with metastatic colorectal cancer selected by MSI-high status benefited greatly from anti–PD-1 [programmed death-1] pembrolizumab, compared with standard of care,” he added.
Dr. André discussed the study in a press briefing prior toof the data as part of the American Society of Clinical Oncology virtual scientific program.
“I think this is setting a new standard of care,” said, of the University of Texas MD Anderson Cancer Center in Houston. Dr. Overman, the invited discussant, commented on the KEYNOTE-177 study in an interview prior to the presentation.
Dr. Overman noted that, although the overall response rate was higher with pembrolizumab, the rate of progressive disease was higher in the pembrolizumab arm than in the chemotherapy arm. Progressive disease was the best response in 29.4% of patients on pembrolizumab and 12.3% of patients on chemotherapy.
“The only area where I think the question on pembrolizumab is still open would be in the group of patients where we’re saying ‘I care about the near future – this patient has so many symptoms and so much disease burden that I care what happens in the short term,’” Dr. Overman said. He added that, for this subgroup of patients, chemotherapy or pembrolizumab in combination with another immunotherapy, such as ipilimumab, might be more appropriate.
Investigators enrolled 307 patients with confirmed, untreated MSI-H/dMMR metastatic colorectal cancer and good performance status (Eastern Cooperative Oncology Group performance status 0 or 1).
Patients were randomized to pembrolizumab at 200 mg every 3 weeks for up to 35 cycles (n = 153) or to the investigators’ choice of chemotherapy (n = 154). Chemotherapy regimens were modified FOLFOX (5-fluorouracil, leucovorin, oxaliplatin) alone or in combination with either bevacizumab or cetuximab, or FOLFIRI (leucovorin, fluorouracil, irinotecan) alone or in combination with either bevacizumab or cetuximab.
Patients assigned to the chemotherapy arm were allowed to cross over to pembrolizumab for up to 35 cycles if they had disease progression confirmed by central review.
PFS is a coprimary endpoint with overall survival. The trial was deemed to be successful if either of the coprimary endpoints was met. Overall survival results are not yet available.
The median PFS was 16.5 months with pembrolizumab and 8.2 months with chemotherapy (hazard ratio, 0.60; P = .0002). The 12-month PFS rates were 55% and 37%, respectively. The 24-month PFS rates were 48% and 19%, respectively.
Overall response rates were 43.8% with pembrolizumab, consisting of 11.1% complete responses and 32.7% partial responses. The overall response rate with chemotherapy was 33.1%, consisting of 3.9% complete responses and 29.2% partial responses.
In all, 20.9% of patients on pembrolizumab and 42.2% of those on chemotherapy had stable disease. Rates of progressive disease were 29.4% and 12.3%, respectively.
The median duration of response was not reached in the pembrolizumab arm and was 10.6 months in the chemotherapy arm. At 2 years, 83% of patients treated with pembrolizumab and 35% treated with chemotherapy had ongoing responses.
Grade 3 or greater treatment-related adverse events occurred in 22% of patients on pembrolizumab and 66% on chemotherapy.
Immune-mediated adverse events and infusion reactions were more common with pembrolizumab than with chemotherapy (31% and 13%, respectively). Adverse events that were common with chemotherapy included gastrointestinal events, fatigue, neutropenia, and peripheral sensory neuropathy.
The study was funded by Merck. Dr. André disclosed relationships with multiple companies, including MSD Oncology. Dr. Overman disclosed consulting activities with various companies, not including Merck.
SOURCE: André T et al. ASCO 2020, .