WASHINGTON — The FDA approved the PD-1 inhibitor pembrolizumab (Keytruda) as initial treatment of metastatic, mismatch repair deficient (dMMR)/microsatellite instability-high (MSI-H) colorectal cancer (CRC).
The first-line indication followed recently reported findings from the KEYNOTE-177 randomized trial showing that patients treated with pembrolizumab lived twice as long without disease progression as compared with patients who received standard chemotherapy. Landmark analyses showed that more than twice as many patients were alive without disease progression at 24 months in the pembrolizumab group.
“Responses were more durable with pembrolizumab versus chemotherapy. We observed an improved safety profile with pembrolizumab versus chemotherapy … Pembrolizumab should be considered a new standard-of-care as first-line therapy with MSI-H metastatic colorectal cancer,” Thierry Andre, MD, of Sorbonne University in Paris, said at a press briefing during the American Society of Clinical Oncology (ASCO) virtual meeting.
ASCO past president Howard A. “Skip” Burris, MD, of Vanderbilt University Medical Center in Nashville, Tennessee, said the findings reflect the concept of using the “best drug first” to treat advanced cancers. “I also think investigators and practitioners will be happy to see that the impact [of first-line pembrolizumab] is pretty substantial.”
The terms dMMR and MSI-H refer to tumors that have a large number of mutations. The FDA previously approved a “tumor-agnostic” indication for pembrolizumab, allowing use of the agent in any type of previously treated solid tumor associated with dMMR/MSI-H. The PD-1 inhibitor nivolumab (Opdivo) and the combination of nivolumab and the CTLA-4 inhibitor ipilimumab (Yervoy) have FDA approval for previously treated dMMR/MSI-H CRC.
KEYNOTE-177 involved 307 patients with previously untreated metastatic dMMR/MSI-H CRC, randomized to pembrolizumab or investigators’ choice of six standard-of-care chemotherapy regimens with or without bevacizumab (Avastin). The trial had co-primary endpoints of progression-free survival (PFS), as assessed by a blinded independent review committee, and overall survival (OS).
After a median follow-up of 28.4 months, patients in the pembrolizumab arm had a median PFS of 16.5 months versus 8.2 months for the chemotherapy arm. The difference represented a 40% reduction in the hazard for disease progression or death. Significantly more patients randomized to the PD-1 inhibitor remained alive without disease progression at 12 and 24 months. Pembrolizumab was substantially better tolerated, as 22% of patients had grade ≥3 adverse events versus 66% of patients in the chemotherapy arm.
Follow-up continues for the co-primary endpoint of OS.
Source: MedicalNewsToday.com
