Background: Adjuvant treatment (tx) of resected stage III BRAF-mutant melanoma with dabrafenib + trametinib (D+T) significantly reduced the risk of recurrence vs placebo (PBO). In the COMBI-AD study, 1-year tx with D+T resulted in improvements in relapse-free survival, distant metastasis-free survival, freedom from relapse, and overall survival.
Objectives: To evaluate and report the effect of D+T on health-related quality of life (HRQOL) in the adjuvant setting.
Methods: COMBI-AD was a randomized, double-blind, phase 3 study evaluating patients (pts) with resected stage III BRAF V600E/K–mutant melanoma. Pts were randomized 1:1 to receive D 150 mg twice daily plus T 2 mg once daily or matching PBOs for 12 months. HRQOL assessment using the EuroQol-5D (EQ-5D-3L) questionnaire and visual analog scale (VAS) was an exploratory end point. A mixed-model, repeated-measures analysis was used to assess differences in mean scores.
Results: A total of 870 pts were randomized (D+T, n = 438; PBO, n = 432). Although pts who were available for assessment had declined during the study primarily due to withdrawal of consent, missed scheduled visits and deaths, the completion rates among available pts were high (98% at baseline [BL], ≥90% throughout the 12-month tx period, and ≥75% at assessments after 12 months). Pts in both arms had similar BL VAS values (D+T, 79.0; PBO, 80.4 [0-100 scale]). During tx (3- to 12-month assessments), VAS scores remained similar to BL, with no clinically meaningful differences observed between arms (adjusted mean change from BL at 12 months: D+T, 0.14; PBO, −0.02). In the D+T arm, no clinically meaningful or statistically significant difference in VAS was reported between pts who did and did not experience pyrexia (P >.1). During follow-up (15-48 months), VAS scores were similar between arms, with no significant or clinically meaningful differences reported. At relapse, a statistically significant reduction in VAS score was observed in both arms (mean difference [pre- vs postrecurrence], D+T, −6.02, P = .003; PBO, −6.84, P <.001).
Conclusions: In the absence of disease-related symptoms in the adjuvant setting, these results demonstrate that D+T do not negatively impact HRQOL during tx or in long-term follow-up and further emphasize the importance to pt HRQOL in preventing relapse.
Note: The COMBI-AD study was sponsored by GlaxoSmithKline; dabrafenib and trametinib are assets of Novartis AG as of March 2, 2015.
This abstract was accepted and previously presented at the 2018 Annual Meeting of the American Society of Clinical Oncology. All rights reserved.
