First-line Pembrolizumab Monotherapy Improves HRQOL Versus Chemotherapy for Metastatic Colorectal Cancer

Matthew Fowler

A phase 3 trial found that pembrolizumab for patients with microsatellite instability–high or mismatch repair–deficient metastatic colorectal cancer significantly improved health-related quality of life compared with chemotherapy.

Patients with previously untreated microsatellite instability–high (MSI-H) or mismatch repair–deficient (MMR-d) metastatic colorectal cancer (CRC) saw clinically significant improvements in their health-related quality of life (HRQOL) when receiving pembrolizumab (Keytruda) monotherapy compared with chemotherapy, according to a study published in Lancet Oncology.

These results from the open-label, randomized, phase 3 KEYNOTE-177 trial (NCT02563002), when combined with previously reported positive clinical data, support the use of pembrolizumab as a first-line therapeutic option for this cohort of patients with metastatic CRC.

“Taken together with previously published efficacy and safety results, these data support the benefits of pembrolizumab as first-line treatment for microsatellite instability–high or mismatch repair–deficient metastatic colorectal cancer,” wrote the investigators. “The significantly improved progression-free survival, lower incidence of treatment-related adverse events, and improvement in HRQOL outcomes with pembrolizumab versus chemotherapy further suggest that pembrolizumab should be considered an option for first-line treatment of these patients.”

The research enrolled 307 patients and randomly assigned them to either pembrolizumab (n = 153) or investigators choice of chemotherapy (n = 154), which included leucovorin, fluorouracil, and either irinotecan or oxaliplatin, with or without bevacizumab (Avastin) or cetuximab (Erbitux). Of this population, 294 patients were included in the HRQOL analysis, with the median time from randomization to data cutoff recorded at 32.4 months as of February 19, 2020.

HRQOL outcomes were measured by mean change from baseline to week 18 by the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (EORTC QLQ-C30) and EORTC Quality of Life Questionnaire-Colorectal 29 (EORTC QLQ-CR29) scale and item scores, as well as in the EuroQoL 5 Dimensions 3 Levels (EQ-5D-3L) visual analogue scale and health utility scores.

Evaluating the least squares mean change from baseline to week 18 found a clinically meaningful improvement in the scores with the EORTC QLQ-C30 global health status/quality of life (GHS/QOL) for patients in the pembrolizumab arm compared with patients in the chemotherapy arm (least squares mean difference, 8.96; 95% CI, 4.24-13.69; 2-sided nominal P = .0002).

More, for GHS/QOL, the median time to deterioration was increased for patients in the pembrolizumab arm versus those in the chemotherapy arm (HR, 0.61; 95% CI, 0.38-0.98; 1-sided nominal P = .019). The same was also true for physical functioning (HR, 0.50; 95% CI, 0.32-0.81; 1-sided nominal P = .0016), social functioning (HR, 0.53; 95% CI 0.32-0.87; 1-sided nominal P = .0050), and fatigue scores (HR, 0.48; 95% CI, 0.33-0.69; 1-sided nominal P < .0001) for patients in the pembrolizumab arm.

“In this analysis of prespecified exploratory HRQOL endpoints from KEYNOTE-177, first-line pembrolizumab was associated with improvements in HRQOL compared with chemotherapy with or without bevacizumab or cetuximab in patients with microsatellite instability-high or mismatch repair-deficient metastatic colorectal cancer,” wrote the investigators.

Patient eligibility required age 18 years and older with MSI-H or MMR-d metastatic CRC, an ECOG performance status of 0 or 1, and no prior systemic therapy for metastatic disease. The patients were then randomized to receive either pembrolizumab 200 mg intravenously every 3 weeks or chemotherapy.

The completion and compliance rates between each arm were the main limitation of the research according to the investigators, potentially impacting the results observed. More, a potential explanation for the difference in compliance rates could be the open-label design causing patients receiving pembrolizumab to be more willing to participate with study investigations.

“The observed improvements in health-related quality of life with pembrolizumab over chemotherapy (with or without bevacizumab or cetuximab) complement the efficacy and safety results of KEYNOTE-177, which showed superior progression-free survival and fewer treatment-related adverse events with pembrolizumab compared with standard-of-care chemotherapy,” wrote the investigators.

Reference:

Andre T, Amonkar M, Norquist JM, et al. Health-related quality of life in patients with microsatellite instability-high or mismatch repair deficient metastatic colorectal cancer treated with first-line pembrolizumab versus chemotherapy (KEYNOTE-177): an open-label, randomised, phase 3 trial. Lancet Oncol. 2021;22(5):665-677. doi:10.1016/S1470-2045(21)00064-4