Keytruda Doubles Progression-Free Survival for Colorectal Cancer Patients with Mutation

Keytruda (pembrolizumab), Merck’s blockbuster immunotherapy drug with more than 20 indication for blood and solid tumor cancers, doubled the rates of progression-free survival (PFS) for certain patients with metastatic colorectal cancer, according to results presented Sunday at the American Society of Clinical Oncology (ASCO) annual meeting.

An interim analysis of the phase 3 KEYNOTE-177 trial, which was funded by the company, found that patients treated with Keytruda had 16.5 months of PFS compared with 8.2 months for patient treated with standard chemotherapy. The patients in study had cancers with the microsatellite instability-high (MSI-H) or a mismatch repair deficient (dMMR) biomarkers that are indications of genomic instability and a greater chance of mutation.

The results will change clinical practice, said lead study author Thierry André, M.D., of the Sorbonne Université and Hôpital Saint Antoine in Paris, during ASCO’s Sunday plenary session.

The findings were a win for the cause of using biomarkers to match patients with the treatment. “It is critical that we test all colorectal cancer patients for mismatch repair or microsatellite status,” said Michael D. Overman, M.D., of the University of Texas MD Anderson Cancer Center. André said, “These data represent another step forward for biomarker-driven studies.”

About 5% of metastatic colon cancer patients have cancers with either the MSI-H or dMMR biomarker. Keytruda’s effectiveness against cancers with those biomarkers led to FDA approving the agent in 2017 as the first “tissue agnostic” anticancer drug, with the presence of the MSI-H or dMMR determining whether it was indicated, not the location of the tumor.

Keytruda might not, though, have much added benefit for colon cancer patients with a short time to live because, as Overman explained, because the Keynote-177 trial showed that the drug’s advantages over conventional chemotherapy didn't become apparent for six months.

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Data cutoff for the interim analysis of the KEYNOTE-177 was February 19, 202. At that time, the study included 307 metastatic colon cancers patients with
MSI-H or dMMR. Patients were randomized to receive first-line Keytruda for up to two years or the investigator’s choice of six different standard chemotherapy regimens. Primary end points were PFS and overall survival. The researchers will continue to evaluate overall survival.

An independent data monitoring committee had previously found statistically significant and clinically meaningful improvement, and called for the trial to continue without changes to the second, co-primary endpoint of overall survival. Patients in the chemotherapy group whose cancer progressed were allowed to cross over into the Keytruda group.

Keytruda patients were also less prone adverse events (AE) of grade 3 or above: 22% had serious AEs, compared with 66% in the chemotherapy group. The most common toxicities in the immunotherapy group were colitis and hepatitis, while chemotherapy-related toxicities were diarrhea, neutropenia, fatigue, nausea, stomatitis, alopecia and neurotoxicitiy.

Reference

Andre T, Shiu KK, Kim TW, et al. First-line therapy of pembrolizumab versus standard of care (SOC) in microsatellite instability-high/mismatch repair deficient metastatic colorectal cancer: The phase III, KEYNOTE-177 study. Presented at: The American Society of Clinical Oncology 2020 Annual Meeting; Alexandria, VA: May 28, 2020. Abstract LBA4