![]() In colorectal cancer specifically, the drug is FDA approved for metastatic or unresectable colorectal cancer patients who are MSI-H or dMMR and who have progressed after chemotherapy treatment with a fluoropyrimidine, oxaliplatin, and irinotecan. The US Food and Drug Administration in 2017 approved pembrolizumab as an option for patients with refractory solid tumors that were MSI-H or otherwise mismatch repair deficient (dMMR), regardless of their cancer histology. In the study, all patients had their MSI-H status established by immunohistochemistry or PCR testing. Keynote-177 started enrolling patients in late 2015, but Diaz explained that it took a long time to recruit the approximately 300 MSI-H metastatic colorectal cancer patients at cancer centers in 23 countries and wait for the progression-free survival endpoint to mature.Īn estimated 4 percent to 5 percent of metastatic colorectal cancer patients are MSI-H, resulting in tumors that are hypermutated due to the cells' impaired ability to repair faulty DNA. The study will continue to evaluate the impact of pembrolizumab on overall survival, but not enough patients have died in the study to report this endpoint. André noted that the toxicity profiles of the two treatment arms differed, with pembrolizumab-treated patients experiencing more immune-mediate adverse events and patients in the comparator arm having more "classical" adverse events associated with chemotherapy, such as diarrhea, neutropenia, fatigue, and nausea. Grade 3 or higher toxicities occurred in 22 percent of patients receiving immunotherapy versus 66 percent in the comparator arm. Keynote-177 also showed pembrolizumab was "significantly safer" in this population than the chemotherapy-containing regimens, Diaz said. Merck highlighted in a statement that these benefits to pembrolizumab were seen in Keynote-177 even though 59 percent of patients crossed over to receive immunotherapy after progressing on a chemo-containing regimen. In the pembrolizumab arm, 83 percent of patients responded to the drug for at least two years versus 35 percent in the chemo arm. Median duration of response was not reached in the pembrolizumab arm but was 10.6 months in the chemo arm. In terms of overall response, 44 percent of patients on pembrolizumab and 33 percent of those on chemo or chemo-containing regimens saw their tumors shrink. After two years of treatment, the median progression-free survival rate was 48 percent and 19 percent, respectively. "It's a pretty impressive scientific and clinical advance."Īfter a year of treatment, 55 percent of patients were alive and not progressing on the pembrolizumab arm compared to 37 percent in the comparator arm. "I think this will be practice changing," added Luis Diaz from Memorial Sloan Kettering Cancer Center, who co-led Keynote-177, in an interview. "In the past, no medical treatment has shown such a difference in improvement of progression-free survival in metastatic colorectal cancer," André said. In a press call hosted by ASCO earlier this week, lead researcher Thierry André from the Saint-Antoine Hospital in Paris reported that at a follow-up of 32 months, median progression-free survival in the pembrolizumab arm was 16.5 months versus 8.2 months in the comparator arm. "The need for new treatments for this population is very high." Despite the availability of chemotherapy and targeted agents, such as bevacizumab and cetuximab, "unfortunately most people will succumb to their disease," he said. "Metastatic colorectal cancer is still an incurable disease for the majority of patients when it has spread beyond the colon to distant organs," Cheng said. Jon Cheng, VP and oncology therapeutic area head at Merck Research Laboratories, highlighted in an interview that pembrolizumab reduced the risk of progression or death by 40 percent compared to chemotherapy-based regimens. The data from this study will be highlighted on May 31, during the plenary session of the American Society of Clinical Oncology's virtual annual meeting. In the Merck-sponsored Keynote-177 trial, metastatic colorectal cancer patients with high microsatellite instability (MSI-H) who received just the checkpoint inhibitor pembrolizumab lived on average twice as long without their disease progressing compared to those who received investigators' choice of chemotherapy alone or a chemotherapy-based regimen that added bevacizumab (Genentech's Avastin) or cetuximab (Eli Lilly's Erbitux). NEW YORK – The results of a Phase III trial may shift the therapeutic landscape for a subset of metastatic colorectal cancer patients, according to several oncologists, and make Merck's pembrolizumab (Keytruda) a new first-line option.
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