MSD’s Keytruda (ingredient: pembrolizumab) extended the progression-free survival (PFS) by two folds in patients with heavily mutated metastatic colorectal cancer as the first-line treatment, compared to the conventional chemotherapy, a study showed.
The results gave a higher chance to Keytruda, instead of Opdivo (nivolumab) by BMS and Ono Pharmaceutical, to become the first-line standard treatment for colorectal cancer patients with microsatellite instability-high (MSI-H) disease or metastatic mismatch repair deficiency (dMMR).
Earlier, Keytruda beat Opdivo and became the first-line treatment for non-small cell lung cancer (NSCLC).
At the virtual meeting of the American Society of Clinical Oncology (ASCO) last week, researchers revealed the interim results of the KEYNOTE-177 study that compared Keytuda with chemotherapy in patients with MSI-H/dMMR metastatic colon cancer.
The study on 307 patients showed that the Keytruda treatment group had 16.5 months in PFS, more than twice that of the chemotherapy group with 8.2 months.
Only 22 percent of the Keytruda-treated patients experienced adverse events of Grade 3 or higher, versus 66 percent of the chemotherapy group, the results showed.
Forty-eight percent of the patients in the Keytruda group survived without disease progression at 24 months, versus 19 percent in the chemo group. The Keytruda group’s objective response rate was 43.8 percent, compared to the chemo group’s 33.1 percent.
The Keytruda-treated group showed 11 percent complete remission (CR), 32.7 percent partial remission (PR), and 20.9 percent stable disease (SD). The chemo group’s CR, PR, and SD stood at 3.9 percent, 29.2 percent, and 42.2 percent, respectively. While 83 percent of the Keytruda group showed treatment response for two years or more, 35 percent of the chemo group did so.
Professor Thierry Andre of Sorbonne University in Paris, who made the presentation, said patients with MSI-H account for about 5 percent of all metastatic colorectal cancer patients. Patients with MSI-H can expect clinical benefits of anti-PD-1 inhibitors, including Keytruda, he said.
Andre noted that Keytruda already proved its antitumor activity and acceptable safety in phase-2 trials in patients with previously treated MSI-H metastatic colorectal cancer.
The U.S. approved Keytruda monotherapy, Opdivo monotherapy, and Opdivo-Yervoy combination therapy as the second-line treatment for patients with MSI-H/dMMR metastatic colorectal cancer.
“Pembrolizumab proved its benefit as the first-line therapy in this randomized, controlled trial. The results are sufficient to support that it should be a new standard of care,” Andre said.
“Immunotherapies like pembrolizumab have proved to be effective as second-line treatments for advanced disease,” said ASCO President Howard A. Burris. “Now, in studies like this one, we are starting to see significant efficacy for immunotherapies as first-line treatment for advanced cancers with specific genetic signatures. The data presented have the potential to change the standard of care.”
MSI-H/dMMR patients have been reported to have weaker DNA repair ability and experience an increase in other genetic mutations. Thus, they are likely to have a lower survival rate and a poor response to conventional chemotherapy.
Keytruda is the only FDA-authorized drug to be used in untreated MSI-H metastatic cancer patients, regardless of tumor type or site.
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