ASCO20 Virtual: Pembrolizumab Doubles Progression-Free Survival for Certain Advanced Colorectal Cancer Types

A study presented at the 2020 American Society of Clinical Oncology (ASCO) Virtual Scientific Program found that pembrolizumab (Keytruda) delivered significant improvement in progression-free survival (PFS) compared with chemotherapy for first-line treatment for microsatellite-instability high/mismatch repair deficient (MSI-H/dMMR) metastatic colorectal cancer (mCRC).^1,2

Presented by lead author Thierry André, MD, Sorbonne Université and Hôpital Saint Antoine in Paris, France, the study results demonstrated that pembrolizumab improved PFS by 16.5 months, compared with chemotherapy without targeted therapy treatment, which demonstrated 8.2 months of PFS.^1,2

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In MSI-H/dMMR, DNA repair is impaired and effectively facilitates mutations. Previous research has estimated that 5% of individuals with metastatic colorectal cancer have high microsatellite instability, therefore exhibiting high levels of mutations. Prior studies have also found MSI-H/dMMR tumors to be associated with decreased survival and patients to be less responsive to chemotherapy.²

Pembrolizumab blocks PD-1 receptor activity in order to allow an individual’s immune system to attack cancer cells. The drug has been approved by the FDA for adult and pediatric patients with previously treated MSI-H metastatic tumors, regardless of tumor type or site, according to the study’s authors.²

The phase 3 KEYNOTE-177 study included 307 treatment-naïve participants with confirmed MSI-H/dMMR stage IV CRC, ECOG performance status (PS) of 0 or 1, and measurable disease. Patients were randomly assigned to receive chemotherapy or 200 mg every 3 weeks for up to 35 cycles or until unacceptable toxicity, disease progression, or patient/physician withdrawal.²

PFS was 55.3% in patients receiving pembrolizumab at 12 months follow up, compared with 37.3% PFS with chemotherapy; at 24 months, 48.3% in the pembrolizumab group showed PFS, compared with 18.6% of the chemotherapy group, according to the results.²

Eleven percent of patients receiving pembrolizumab experienced complete response and no detectable cancer; 32.7% experienced reduced tumor size (partial response); 30.9% showed stable disease. On the other hand, 3.9% of those receiving chemotherapy showed complete response; 29.2% had a partial response; 42.2% maintained stable disease.²

The pembrolizumab group additionally experienced less frequent severe adverse events (AEs) related to treatment compared to the chemotherapy group, with 22% of pembrolizumab patients having severe AEs compared with 66% of those receiving chemotherapy.²

“These long-awaited trial results will change clinical practice,” said André during the ASCO20 virtual press briefing. “Pembrolizumab works in non-randomized studies in this group of patients with advanced disease. This randomized study demonstrates a huge benefit in first line with pembrolizumab and should be the new standard of care.”2

References:

1. Andre T, Shiu K, Kin TW, et al. Pembrolizumab versus chemotherapy for microsatellite instability-high/mismatch repair deficient metastatic colorectal cancer: The phase 3 KEYNOTE-177 study. Presented at 2020 American Society of Clinical Oncology Virtual Scientific Program; May 29-31; online.
2. Pembrolizumab Doubles Time to Disease Progression in Patients With Advanced Colorectal Cancer With Specific DNA Mutations. News Release. ASCO; May 28, 2020. Accessed May 29. 2020. https://www.asco.org/about-asco/press-center/news-releases/pembrolizumab-doubles-time-disease-progression-patients.