In an analysis from the phase III KEYNOTE-177 trial reported in The Lancet Oncology, Thierry André, MD, and colleagues found that pembrolizumab was associated with clinically meaningful improvements in health-related quality of life (HRQOL) compared with chemotherapy in the first-line treatment of microsatellite instability–high (MSI-H) or mismatch repair–deficient (dMMR) metastatic colorectal cancer.
In the trial, pembrolizumab was associated with significantly prolonged progression-free survival (co-primary endpoint) vs chemotherapy. Findings on overall survival (co-primary endpoint) have yet to be reported.
Pembrolizumab monotherapy led to clinically meaningful improvements in HRQOL compared with chemotherapy in patients with previously untreated MSI-H or dMMR metastatic colorectal cancer. These data, along with the previously reported clinical benefits, support pembrolizumab as a first-line treatment option for this population.— Thierry André, MD, and colleagues
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Study Details
In the open-label trial, 307 patients were randomly assigned to receive pembrolizumab (n = 153) or investigator’s choice of chemotherapy consisting of mFOLFOX6 (leucovorin, fluorouracil [5-FU], and oxaliplatin) or FOLFIRI (leucovorin, 5-FU, and irinotecan) with or without bevacizumab or cetuximab (n = 154). The HRQOL analysis population consisted of 294 patients, including 152 in the pembrolizumab group and 142 in the chemotherapy group.
HRQOL assessment included mean change from baseline to prespecified week 18 in EORTC Quality of Life Questionnaire Core 30 (EORTC QLQ-C30) global health status/quality of life (GHS/QOL) and in the EuroQoL 5 Dimensions 3 Levels (EQ-5D-3L) visual analog scale, as well as health utility scores and time to deterioration over follow-up in GHS/QOL overall score and physical functioning, social functioning, and fatigue scores, and EORTC QLQ-Colorectal 29 (CR29) urinary incontinence score. The threshold for a small and clinically meaningful mean difference in EORTC QLQ-C30 GHS/QOL score was defined as 5 to 8 points.
Key Findings
Median time from random assignment to data cutoff was 32.4 months. Least squares mean (LSM) changes from baseline to week 18 in EORTC QLQ-C30 GHS/QOL scores were +3.33 in the pembrolizumab group vs –5.63 in the chemotherapy group; the between-group LSM difference was 8.96 (95% confidence interval [CI] = 4.24–13.69, P = .0002), meeting the criterion of a clinically meaningful difference.
Improvement was observed for the pembrolizumab group vs the chemotherapy group on the EQ-5D-3L visual analog scale at 18 weeks (between-group LSM difference = 7.38, 95% CI = 2.82–11.93, P = .0016), but not on the EQ-5D-3L health utility score (0.05, 95% CI = 0.00–0.10, P = .031).
Median time to deterioration was longer with pembrolizumab vs chemotherapy for GHS/QOL overall (hazard ratio [HR] = 0.61, 95% CI = 0.38–0.98, P = .019) and in the physical functioning (HR = 0.50, 95% CI = 0.32–0.81, P = .0016), social functioning (HR = 0.53, 95% CI = 0.32–0.87, P = .0050), and fatigue scores (HR = 0.48, 95% CI = 0.33–0.69, P < .0001). No significant difference was observed in time to deterioration in the EORTC QLQ-CR29 urinary incontinence score (HR = 0.43, 95% CI = 0.14–1.31, P = .064).
The investigators concluded, “Pembrolizumab monotherapy led to clinically meaningful improvements in HRQOL compared with chemotherapy in patients with previously untreated MSI-H or dMMR metastatic colorectal cancer. These data, along with the previously reported clinical benefits, support pembrolizumab as a first-line treatment option for this population.”
Dr. Andre, of Sorbonne Université and Hôpital Saint-Antoine, Paris, is the corresponding author for The Lancet Oncology article.
Disclosure: The study was funded by Merck Sharp & Dohme, a subsidiary of Merck & Co. For full disclosures of the study authors, visit thelancet.com.
