As reported in The Lancet Oncology by Andrew Bottomley, PhD, and colleagues, an analysis of the phase III EORTC 1325-MG/KEYNOTE-054 trial showed no clinically significant decline in health-related quality of life (HRQoL) with adjuvant pembrolizumab vs placebo in resected high-risk stage III melanoma.
The trial showed significantly improved recurrence-free survival with pembrolizumab (hazard ratio = 0.57, 98.4% confidence interval [CI] = 0.43–0.74, P < .0001).
Pembrolizumab does not result in a clinically significant decrease in HRQoL compared with placebo when given as adjuvant therapy for patients with resected, high-risk stage III melanoma. These results support the use of adjuvant pembrolizumab in this setting.— Andrew Bottomley, PhD
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Study Details
In the double-blind trial, 1,019 patients from sites in 23 countries were randomly assigned between August 2015 and November 2016 to receive pembrolizumab at 200 mg (n = 514) or placebo (n = 505) every 3 weeks for up to 18 doses or until disease recurrence or unacceptable toxicity. HRQoL was assessed as global health/quality of life (GHQ; transformed 1–100 scale) over 2 years on the EORTC Quality of Life Questionnaire (QLQ)-C30. The EORTC QLQ-C30 was completed at baseline and every 12 weeks after starting treatment for the first 2 years, regardless of disease recurrence or treatment discontinuation.
Analysis was performed in the intention-to treat population, with imputation of missing values. A between-group difference of 5 points in GHQ score was defined as clinically significant.
Key Findings
Median follow-up was 15.1 months (interquartile range = 12.8–16.9 months) at the time of the analysis. HRQoL compliance was > 90% at baseline, > 70% during the first year, and > 60% thereafter in both groups. Due to low absolute compliance numbers during later follow-up, the analysis was truncated at 84 weeks.
Baseline mean GHQ scores were similar for the pembrolizumab group vs the placebo group (77.55 vs 76.54) and remained stable over time. Mean scores were 75.89 vs 77.99 at 12 weeks, 76.27 vs 77.42 at 24 weeks, 75.21 vs 76.98 at 36 weeks, 76.62 vs 76.91 at 48 weeks, 76.81 vs 78.08 at 60 weeks, 78.94 vs 78.67 at 72 weeks, and 81.43 vs 80.05 at 84 weeks.
The mean GHQ scores over 2 years were 75.1 vs 77.3, yielding a difference of –2.2 points (95% CI = –4.3 to –0.2 points). The mean scores during pembrolizumab and placebo treatment were 76.9 vs 78.0, yielding a difference of –1.1 points (95% CI = –3.2 to 0.9 points). The mean scores after treatment were 75.0 vs 77.2, yielding a difference of –2.2 points (95% CI = –4.8 to 0.4 points). None of the differences reached the 5-point clinical relevance threshold and were thus considered clinically nonsignificant.
The investigators concluded, “Pembrolizumab does not result in a clinically significant decrease in HRQoL compared with placebo when given as adjuvant therapy for patients with resected, high-risk stage III melanoma. These results support the use of adjuvant pembrolizumab in this setting.”
Dr. Bottomley, of EORTC Headquarters, Brussels, is the corresponding author for The Lancet Oncology article.
Disclosure: The study was funded by Merck Sharp & Dohme. For full disclosures of the study authors, visit thelancet.com.
