|The following article features coverage from the 2021 American Society of Clinical Oncology (ASCO) Annual Meeting. Click here to read more of Cancer Therapy Advisor‘s conference coverage.|
Pembrolizumab significantly improved progression-free survival (PFS), but not overall survival (OS), when compared with chemotherapy in patients with microsatellite instability-high (MSI-H) or mismatch repair-deficient (dMMR) metastatic colorectal cancer (mCRC), according to final results of the KEYNOTE-177 study.
The results were presented at the 2021 American Society of Clinical Oncology (ASCO) Annual Meeting by Thierry Andre, MD, of Sorbonne Université and Hôpital-Saint Antoine in Paris.
The phase 3 KEYNOTE-177 trial (ClinicalTrials.gov Identifier: NCT02563002) was designed to compare pembrolizumab to investigators’ choice of chemotherapy as first-line treatment in patients with MSI-H/dMMR mCRC.
Chemotherapy regimens included mFOLFOX6 (5-fluorouracil, leucovorin, and oxaliplatin), mFOLFOX6 plus either bevacizumab or cetuximab, FOLFIRI (5-fluorouracil, leucovorin, and irinotecan), and FOLFIRI plus either bevacizumab or cetuximab.
A total of 307 patients were randomly assigned 1:1 to receive 200 mg of pembrolizumab every 3 weeks for up to 2 years or chemotherapy once every 2 weeks. Patients in the chemotherapy arm who had confirmed progressive disease were allowed to cross over to the pembrolizumab arm.
The data cutoff for the final analysis was February 19, 2021. The median follow-up for the pembrolizumab and chemotherapy arms was 44.5 months and 44.4 months, respectively.
There were 56 patients (36%) who had crossed over from the chemotherapy arm to the pembrolizumab arm. An additional 37 patients (24%) received other anti-PD-1/PD-L1 therapy outside of the study, so the effective crossover rate was 60% in the intent-to-treat population.
At the final analysis, there was a trend toward reduced mortality with pembrolizumab, but statistical significance was not met. This may have been due to the high crossover rate, according to the researchers.
The median OS was not reached in the pembrolizumab arm and was 36.7 months in the chemotherapy arm (hazard ratio [HR] 0.74; 95% CI, 0.53-1.03; P =.0359). The 36-month OS rate was 61% and 50%, respectively.
The median PFS was superior in the pembrolizumab arm compared with the chemotherapy arm — 16.5 months and 8.2 months, respectively (HR, 0.59; 95% CI, 0.45-0.79). The 36-month PFS was 42% and 11%, respectively.
The median PFS2 (time from randomization to progression on next line of therapy or death from any cause) was 54.0 months in the pembrolizumab arm and 24.9 months in the chemotherapy arm (HR, 0.61; 95% CI, 0.44-0.83). The 36-month PFS2 was 60% and 39%, respectively.
The confirmed overall response rate (ORR) for pembrolizumab was 45.1%, which included 20 complete responses (CRs) and 49 partial responses (PRs). The ORR in the chemotherapy arm was 33.1%, which included 6 CRs and 45 PRs.
The median duration of response was not reached in the pembrolizumab arm and was 10.6 months in the chemotherapy arm.
Fewer treatment-related adverse events (TRAEs) occurred in the pembrolizumab arm (79.7%) compared with the chemotherapy arm (98.6%). Grade 3 or higher TRAEs were observed in 21.6% of patients in the pembrolizumab arm and 66.4% of patients in the chemotherapy arm.
“[P]embrolizumab provided a statistically significant improvement in PFS versus chemo as first-line therapy for MSI-high metastatic colorectal cancer, with … less treatment-related events and better quality of life,” Dr Andre said. “Pembrolizumab should be the new standard of care for these patients.”
Disclosure: This research was supported by Merck & Co., Inc. Some study authors declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of authors’ disclosures.
Read more of Cancer Therapy Advisor’s coverage of the 2021 ASCO Annual Meeting by visiting the conference page.
Andre T, Shiu K-K, Kim TW, et al. Final overall survival for the phase III KN177 study: pembrolizumab versus chemotherapy in microsatellite instability-high/mismatch repair deficient (MSI-H/dMMR) metastatic colorectal cancer (mCRC). J Clin Oncol. 2021;39:(suppl 15; abstr 3500). doi:10.1200/JCO.2021.39.15_suppl.3500