Crossing survival curves of KEYNOTE-177 illustrate the rationale behind combining immune checkpoint inhibition with chemotherapy – Authors' reply

In their letter, David Bomze and colleagues note that the restricted mean survival time provides an alternative approach to quantify treatment effect, and they estimate that 21% of patients included in KEYNOTE-177 had inferior overall survival with first-line pembrolizumab compared with first-line chemotherapy. We believe that these data highlight the need to investigate the molecular underpinnings of PD-1 resistance, and how best to overcome this resistance. 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 trialPembrolizumab monotherapy led to clinically meaningful improvements in HRQOL compared with chemotherapy in patients with previously untreated microsatellite instability-high or mismatch repair-deficient metastatic colorectal cancer. These data, along with the previously reported clinical benefits, support pembrolizumab as a first-line treatment option for this population. Full-Text PDF Crossing survival curves of KEYNOTE-177 illustrate the rationale behind combining immune checkpoint inhibition with chemotherapyWe commend Luis A Diaz Jr and colleagues1 for using restricted mean survival time, a robust, non-parametric alternative method to quantify an effect size when conducting a time-to-event analysis, on the KEYNOTE-177 trial. The restricted mean survival time difference is the area bounded by two Kaplan-Meier curves, and reflects the absolute gain, or loss, in survival.2 The authors report that the restricted mean survival time for overall survival after 36 months of follow-up was 26·6 months in the pembrolizumab group and 25·0 months in the chemotherapy group—a difference of 1·6 months. Full-Text PDF