Pembrolizumab with trastuzumab and chemotherapy for HER2-positive advanced gastric cancer: health-related quality-of-life analysis from the randomized KEYNOTE-811 trial

Abstract

Background: In the primary analysis of the randomized phase III KEYNOTE-811 trial (NCT03615326), pembrolizumab plus trastuzumab and chemotherapy improved progression-free survival and overall survival versus placebo plus trastuzumab and chemotherapy in participants with previously untreated human epidermal growth factor receptor 2 (HER2)-positive advanced gastric cancer. Patients and methods: Overall, 698 participants were randomly assigned (1 : 1) to pembrolizumab 200 mg or placebo every 3 weeks, both with trastuzumab and chemotherapy. We report prespecified exploratory patient-reported outcomes (PROs), including change from baseline, time to deterioration (TTD), and overall improvement/stability rate assessed in European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-Core 30 (EORTC QLQ-C30) scales/items, EORTC Quality of Life Questionnaire-Stomach 22 pain scale, and EuroQoL 5-dimension 5-level questionnaire visual analog scale. Results: The PRO population comprised 685 participants. At baseline, the rates of compliance and completion for all PRO questionnaires and for both treatment groups were >92%; at week 24, the rates were >80% and >55%, respectively. No between-group differences were observed from baseline to week 24 for the QLQ-C30 global health status/quality of life (GHS/QoL) scale [least squares mean (LSM) difference-1.16; 95% confidence interval (CI)-4.23 to 1.91] and EQ VAS (LSM difference,-0.69; 95% CI-3.06 to 1.68). Median TTD was not reached. A similar proportion of participants in each treatment group had improved and/or stable scores in the QLQ-C30 GHS/ QoL scale (pembrolizumab group 71.9%; placebo group 71.5%). Findings were similar for all other prespecified scales/items. Conclusions: While improving clinical outcomes, the addition of pembrolizumab to trastuzumab and chemotherapy did not negatively impact health-related quality of life during treatment, supporting the use of pembrolizumab plus trastuzumab and chemotherapy for first-line treatment of HER2-positive advanced gastric cancer.