Pembrolizumab does not result in a clinically significant decrease in health-related quality of life (HRQOL) compared with placebo when it is administered as adjuvant therapy in patients with resected, high-risk stage III melanoma, according to a study published in The Lancet Oncology.
Investigators reported results from the HRQOL exploratory endpoint of the European Organisation for Research and Treatment of Cancer (EORTC) 1325-MG/KEYNOTE-054 trial (ClinicalTrials.gov Identifier: NCT02362594). The double-blind, randomized, controlled, phase 3 trial was conducted at 123 academic centers and community hospitals in 23 countries.
Participants were aged 18 years or older with histologically confirmed cutaneous melanoma with metastasis to regional lymph nodes (stage IIIA, IIIB, or IIIC disease). The participants received an intravenous infusion of 200 mg of pembrolizumab or placebo every 3 weeks for a total of 18 doses or until disease recurrence, unacceptable toxic effects, a major protocol violation, or withdrawal of consent. Global health/quality of life (GHQ) was the main HRQOL endpoint during the first 2 years of study treatment.
A total of 1019 patients were randomly assigned to either pembrolizumab (514 patients) or placebo (505 patients) from August 26, 2015 to November 14, 2016. The overall median follow-up was 15.1 months (interquartile range, 12.8-16.9). Analysis was shortened to week 84 because of low absolute compliance numbers at subsequent follow-up.
The baseline mean GHQ score was 77.55 (standard deviation [SD], 18.20) for participants in the pembrolizumab group and 76.54 (SD, 17.81) for those in the placebo group. Overall treatment differences between the 2 groups regarding the GHQ scale from baseline to 2 years were significant but not clinically relevant (-2.2 points; 95% CI, -4.3 to -0.2; P =.042). Treatment differences for participants’ average score during treatment and after treatment were not statistically or clinically significant according to the GHQ scale. GHQ scores at assessments after baseline were similar at all time points for the 2 treatment groups.
The difference in average score between the pembrolizumab or placebo groups was -1.1 points (95% CI, -3.2 to 0.9), and the difference in average score after treatment was -2.2 points (-4.8 to 0.4).
The researchers noted that their findings are limited due to missing data. Also, no module was used to assess the specific symptoms observed in patients with resected, high-risk stage III melanoma, and some symptoms may be better assessed by using a specific instrument.
“Differences in HRQOL between groups and over time remained below the clinical relevance threshold, thus demonstrating no clinically relevant impairment on patients’ HRQOL in the treatment group and supporting the use of pembrolizumab in patients with resected stage III melanoma,” the study authors concluded.
Disclosures: This clinical trial was supported by Merck Sharp & Dohme. Several study authors declared affiliations with the pharmaceutical industry. Please see the original reference for a full list of authors’ disclosures.
Bottomley A, Coens C, Mierzynska J, et al.Adjuvant pembrolizumab versus placebo in resected stage III melanoma (EORTC 1325-MG/KEYNOTE-054): health-related quality-of-life results from a double-blind, randomised, controlled, phase 3 trial. Lancet Oncol. Published online April 12, 2021. doi:10.1016/S1470-2045(21)00081-4