A secondary analysis from the phase 3 SWOG S1404 trial indicated that adjuvant pembrolizumab yielded improved patient-reported outcomes compared with high-dose interferon α or ipilimumab in the treatment of patients with high-risk resected melanoma.
Pembrolizumab (Keytruda) improved quality-of-life outcomes compared with standard-of-care high-dose interferon α or ipilimumab (Yervoy) among patients with high-risk resected melanoma, according to results from a secondary analysis of the phase 3 SWOG S1404 trial (NCT02506153).
Estimates of Functional Assessment of Cancer Therapy (FACT) Biological Response Modifiers (FACT-BRM) trial outcome index (TOI) for cycle 3 compliance was 96.0% in the ipilimumab/interferon α arm and 98.3% in the pembrolizumab arm (P = .25). Moreover, the adjusted cycle 3 FACT-BRM TOI score was 9.6 points (95% CI, 7.9-11.3; P <.001) higher for patients treated with pembrolizumab vs those who received standard-of-care treatment, surpassing the prespecified clinically meaningful difference of 5 points.
Linear-mixed model analyses favored pembrolizumab by more than 5 points through cycle 7. Additionally, post hoc analyses indicated higher FACT-BRM TOI scores in the pembrolizumab cohort by 6.0 points (95% CI, 4.1-7.8; P <.001) compared with patients receiving ipilimumab and a difference of 17.0 points (95% CI, 14.6-19.4; P <.001) compared with those receiving high-dose interferon α.
Investigators of the international phase 3 SWOG S1404 clinical trial randomly assigned patients with resected melanoma 1:1 to receive either adjuvant pembrolizumab or standard of care ipilimumab or high-dose interferon α. Quality-of-life assessments were conducted at baseline; after treatment cycles 1, 3, 5, 7, and 9; and 24 and 48 weeks after discontinuation of study treatment. Assessment scores included FACT-BRM, FACT-General, Functional Assessment of Chronic Illness Therapy-Diarrhea, and European Quality of Life 5-Dimension 3-Level scales.
The primary end point of the trial was the FACT-BRM TOI score at cycle 3 using linear regression among all patients evaluable for quality-of-life assessment. The study’s design focused on the experience of all evaluable patients undergoing active treatment.
Patients with stage IIIA, N2a, IIIB, IIIC, or IV melanoma of nonocular origin as determined by American Joint Committee on Cancer 7th edition guidelines who had undergone complete surgical resection were eligible to enroll on the trial.
Study investigators enrolled a total of 1345 patients, 42 of whom were ineligible. Patients were randomly assigned to receive either standard-of-care (n = 678) or the pembrolizumab arm (n = 667). A total of 267 patients in the standard-of-care arm were evaluable for the trial’s primary end point vs 565 in the pembrolizumab cohort.
At baseline, the median age of all eligible patients was 56.7 years (range, 18.3-86.0) and most patients were male (59.8%) and younger than 65 years (74.4%). The trial investigators observed no statistically significant differences in baseline characteristics between patients who did and did not have scores available cycle 3 for FACT-BRM TOI. Moreover, most patients were White (95.4%) and non-Hispanic (93.9%).
A post hoc analysis of quality-of-life measures highlighted statistically significant differences exceeding the target threshold of 5 points in favor of pembrolizumab across all categories of stratification variables. An exception to this pattern was among patients with PD-L1 indeterminate status, which the trial investigators attributed to small numbers and limited power (6.9 points; 95% CI, –3.4 to 17.2; P = .18).
Unger JM, Darke A, Othus M, et al. Effectiveness of adjuvant pembrolizumab vs high-dose interferon or ipilimumab for quality-of-life outcomes in patients with resected melanoma: a secondary analysis of the SWOG S1404 randomized clinical trial. JAMA Oncol. Published online November 23, 2022. doi:10.1001/jamaoncol.2022.5486