An interim analysis of the KEYNOTE-716 trial of adjuvant pembrolizumab supports its use in the adjuvant setting for patients with resected melanoma.
In the KEYNOTE-716 trial of adjuvant pembrolizumab vs placebo in resected high-risk stage II melanoma, pembrolizumab improved recurrence-free survival (RFS). Health-related quality-of-life (HRQOL) results from a second interim analysis suggest integrating pembrolizumab does not negatively affect HRQOL and support its use in this disease setting.
The standard of care for melanoma was resection and observation until recently, with adjuvant therapy only recommended in clinical trials. But in KEYNOTE-716, pembrolizumab significantly reduced the risk of recurrence. Patients given pembrolizumab had a hazard ratio of 0.61 (95% CI, 0.46-0.92; P = .00658) vs the placebo group at an interim analysis, and the results led to pembrolizumab’s FDA approval for patients with stage IIb or IIc melanoma in the adjuvant setting. The HRQOL implications are important, however, considering some patients may be cured with surgery alone. Findings from a second interim analysis on HRQOL were presented at the 2022 American Society of Clinical Oncology Annual Meeting.
A total of 969 patients (483 on the pembrolizumab regimen and 486 in the placebo group) were included in the HRQOL portion of the study, which enrolled 976 patients aged 12 or older with resected IIb or IIc melanoma. Patients were randomized 1:1 to placebo or pembrolizumab. HRQOL effects were an exploratory end point in the study.
The patients in the HRQOL analysis all received at least 1 dose of pembrolizumab or placebo and had HRQOL assessments available. The European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire Core 30 (QLQ-C30) was used throughout the study to gauge HRQOL. Improvements in global health status (GHS)/QOL, or physical functioning (PF) scales were considered improvements in HRQOL. The EQ-5D-5L visual analog scale (VAS), which ranges from 0 to 100 (worst to best health imaginable), was also used. Least-squares mean (LSM) changes from baseline were calculated to determine HRQOL impacts.
In the intent-to-treat (ITT) population, the median follow-up was 20.5 months and adherence to EORTC QLQ-C30 assessments was 83.4% for the pembrolizumab cohort and 89.3% in the placebo cohort at week 48. At completion, compliance was 70.6% and 75.7%, respectively. EQ-5D-5L adherence was 84.1% and 90% at week 48 in the pembrolizumab and placebo cohorts, respectively. At completion, adherence was 71.2% and 76.3%.
From baseline to week 48, the LSM change in QLQ-C30 GHS/QOL was –4.49 in the pembrolizumab group and –0.82 in the placebo group. The LSM changes in QLQ-C30 PF scores were –3.27 and –1.77, respectively. The LSM change in EQ-5D-5L VAS score at week 48 was –2.19 in the treatment group and –0.25 in the placebo group.
Overall, there was no clinically significant decline in HRQOL in the pembrolizumab cohort based on the EORTC QLQ-C30 or EQ-5D-5L VAS scores after 48 weeks of adjuvant therapy. These findings are in line with HRQOL data from the KEYNOTE-054 trial of adjuvant pembrolizumab in patients with high-risk resected stage III melanoma.
Considering the improved RFS and safety data, these HRQOL findings further support the use of adjuvant pembrolizumab after resection in patients with high-risk stage II melanoma.
Khattak MA, Luke JJ, Long GV, et al. Health-related quality of life (HRQoL) with pembrolizumab (pembro) in resected high-risk stage II melanoma in the phase 3 KEYNOTE-716 study. Abstract presented at: 2022 American Society of Clinical Oncology Annual Meeting; June 3-7, 2022; Chicago, IL. Abstract 9581. Accessed June 23, 2022. https://meetings.asco.org/abstracts-presentations/209202