Pembrolizumab Induces Significantly Improved PFS in MSI-H/dMMR Colorectal Cancer

The phase III KEYNOTE-177 trial designed to evaluate first-line pembrolizumab (Keytruda) in patients with microsatellite instability-high (MSI-H) or mismatch repair deficient (dMMR) unresectable or metastatic advanced colorectal cancer met 1 of its dual primary endpoints of progression-free survival (PFS), according to Merck, the agent’s developer.

Based on an interim analysis conducted by an independent data monitoring committee (DMC), pembrolizumab monotherapy was found to demonstrate a statistically significant and clinically meaningful improvement in PFS compared with chemotherapy. 

The company indicated that they will be presenting data from this study at an upcoming medical congress. 

“These head-to-head data with Keytruda are the first time a single-agent, anti-cancer therapy, and particularly an anti-PD-1 monotherapy, achieved a statistically significant improvement in progression-free survival over chemotherapy, including the current standard of care regimen of mFOLFOX6 plus bevacizumab [Avastin], in patients with MSI-H colorectal cancer,” Roy Baynes, senior vice president and head of global clinical develop, as well as chief medical officer at Merck Research Laboratories, said in a press release. “These data in the first-line treatment setting provide further evidence of the benefits of Keytruda monotherapy in patients whose tumors are MSI-H or dMMR. We look forward to sharing these data as quickly as possible with the medical community and regulatory authorities.”

The safety profile of pembrolizumab in this trial was consistent with previously reported studies, and no new safety signals were identified. Moreover, based on the recommendation of the DMC, KEYNOTE-177 will continue without changes to evaluate overall survival (OS), the other dual primary endpoint.

In the randomized, open-label, phase III study, the secondary endpoint is overall response rate (ORR). Overall, 308 patients were randomized to either 200 mg of pembrolizumab every 3 weeks for up to 35 cycles of treatment (up to approximately 2 years) or investigator’s choice of one of the following chemotherapy-based regimens:

• mFOLFOX6

• mFOLFOX6 plus bevacizumab (5 mg/kg IV on day 1 of each 2-week cycle)

• mFOLFOX6 plus cetuximab [Erbitux] (400 mg/m² IV, then 250 mg/m² weekly in each 2-week cycle)

• FOLFIRI

• FOLFIRI plus bevacizumab (5 mg/kg IV on day 1 of each 2-week cycle)

• FOLFIRI plus cetuximab (400 mg/m² IV, then 250 mg/m² weekly in each 2-week cycle)

In May 2017, pembrolizumab became the first cancer therapy approved by the FDA for use based on a biomarker, regardless of tumor type, in previously treated patients with MSI-H or dMMR solid tumors. 

Pembrolizumab is an anti-PD-1 therapy that operates by increasing the ability of the body’s immune system to help detect and fight tumor cells. Currently, there are more than 1,200 trials studying pembrolizumab across a wide variety of cancer types and treatment settings. 

Reference:

Merck Announces Keytruda (pembrolizumab) Significantly Improved Progression-Free Survival as First-Line Treatment for Advanced Microsatellite Instability-High (MSI-H) or Mismatch Repair Deficient (dMMR) Colorectal Cancer [news release]. Kenilworth, New Jersey. Published April 2, 2020. mrknewsroom.com/news-release/oncology/merck-announces-keytruda-pembrolizumab-significantly-improved-progression-free. Accessed April 2, 2020.