Immuno-Oncology Resource Center

Immuno-Oncology Resource Center

June 30, 2020
2 min read

FDA approves Keytruda as first-line treatment for colorectal cancer subtype

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The FDA approved pembrolizumab for first-line treatment of patients with unresectable or metastatic microsatellite instability-high or mismatch repair-deficient colorectal cancer.

Approximately 5% of patients with metastatic colorectal cancer have metastatic microsatellite instability-high or mismatch repair-deficient tumors.

“Metastatic colorectal cancer is a serious and life-threatening disease with a poor prognosis. Available current therapy with chemotherapy combinations and other biologics are associated with substantial toxicity,” Richard Pazdur, MD, director of the FDA’s Oncology Center of Excellence and acting director of the Office of Oncologic Diseases in the FDA’s Center for Drug Evaluation and Research, said in a press release.

Richard Pazdur
Richard Pazdur

“Having a nonchemotherapy option available for selected patients is a noteworthy paradigm shift in treatment,” he added. 

The FDA reviewed the supplemental biologics license application for pembrolizumab (Keytruda, Merck), an anti-PD-1 therapy, through its Real-Time Oncology Review pilot program and Project Orbis, which provides a framework for concurrent submission and review of oncology drug applications among international agencies.

“[This] approval has the potential to change the treatment paradigm for the first-line treatment of patients with [microsatellite instability-high] colorectal cancer, based on the important findings from KEYNOTE-177 that showed Keytruda monotherapy demonstrated superior PFS compared with standard-of-care chemotherapy,” Roy Baynes, MD, PhD, senior vice president, head of global clinical development and chief medical officer at Merck Research Laboratories, said in a Merck-issued press release. “Our commitment to pursuing biomarker research continues to help us bring new treatments to patients, particularly for those who have few available options.”

In the phase 3 KEYNOTE-177 trial, researchers randomly assigned 307 patients (median age, 63 years; 50% women) with previously untreated microsatellite instability-high or mismatch repair-deficient colorectal cancer to pembrolizumab dosed at 200 mg every 3 weeks (n = 153) or investigator’s choice of one of six standard chemotherapy regimens selected prior to randomization (n = 154). These included modified FOLFOX-6, which consists of 5-FU, leucovorin and oxaliplatin; modified FOLFOX-6 plus bevacizumab (Avastin, Genentech); modified FOLFOX-6 plus cetuximab (Erbitux, Eli Lilly); FOLFIRI, which consists of leucovorin, 5-FU and irinotecan; FOLFIRI plus bevacizumab; or FOLFIRI plus cetuximab.

Treatment continued until disease progression, unacceptable toxicity, patient or investigator decision to withdraw, or — in the case of pembrolizumab — completion of 35 cycles. Patients assigned chemotherapy who developed confirmed progressive disease could cross over to pembrolizumab for up to 35 cycles.

PFS by blinded independent central review and OS served as primary endpoints. Key secondary endpoints included overall response rate and safety.


Results, presented during the ASCO20 Virtual Scientific Program in May, showed a near-doubling of median PFS with pembrolizumab (16.5 months vs. 8.2 months; HR = 0.6; 95% CI, 0.45-0.8). A higher percentage of patients assigned pembrolizumab remained progression free at 12 months (55.3% vs. 37.3%) and 24 months (48.3% vs. 18.6%).

Researchers also reported a higher ORR in the pembrolizumab group (43.8% vs. 33.1%), as well as higher rates of complete response (11.1% vs. 3.9%) and partial response (32.7% vs. 29.2%).

The most common adverse reactions among patients who received pembrolizumab monotherapy included fatigue, diarrhea, nausea, musculoskeletal pain, decreased appetite, pruritus, rash, pyrexia, cough, dyspnea, constipation and abdominal pain.

“Patients with unresectable or metastatic [microsatellite instability-high] colorectal cancer have historically faced poor outcomes, and until today, chemotherapy-containing regimens were the only FDA-approved first-line treatment options,” Luis A. Diaz, MD, head of the division of solid tumor oncology at Memorial Sloan Kettering Cancer Center, said in the Merck press release. “This approval helps address the unmet need to provide a new monotherapy treatment option for patients.”