Health-related quality-of-life (HRQOL) impact of dabrafenib (D) and trametinib (T) vs BRAF inhibitor (BRAFi) monotherapy by lactate dehydrogenase (LDH) in patients (pts) with BRAF V600–mutant melanoma

Abstract

Background: D + T improved outcomes and HRQOL in pts with BRAF V600‐mutant melanoma vs BRAFi alone in COMBI‐d (NCT01584648) and COMBI‐v (NCT01597908). Although pooled analysis of melanoma clinical/prognostic characteristics across D + T registration trials identified baseline (BL) LDH as the most influential covariate on outcomes, D + T improved response, PFS, and OS vs BRAFi alone in both normal and elevated‐LDH groups. This retrospective analysis of COMBI‐d and COMBI‐v patient‐reported outcomes (PROs) assessed whether HRQOL was consistently improved across LDH groups. Methods: COMBI‐d and COMBI‐v are phase 3, randomized, double‐blind studies of first‐line D + T vs D + placebo (Pbo) or vemurafenib (V), respectively, in pts with unresectable stage IIIC or IV BRAF V600‐mutant melanoma. HRQOL was evaluated in COMBI‐d and COMBI‐v by EORTC QLQ‐C30 (global QOL, functional, and symptom domains) at BL, during treatment (Tx), and at disease progression (PD). PROs were analyzed by LDH (≤ and > ULN). ANCOVA adjusted for BL score using mixed‐model repeated measures was carried out. Results: Across COMBI‐d (D + T, n = 211 [77 with LDH > ULN]; D + Pbo, n = 212 [71 with LDH > ULN]) and COMBI‐v (D + T, n = 352 [118 with LDH > ULN]; V, n = 352 [114 with LDH > ULN]), EORTC QLQ‐C30 completion rates were > 85% through wk 40 and ≥ 70% at PD. Clinically meaningful differences in mean scores between arms favoring D + T vs BRAFi alone were seen for most HRQOL domains for both LDH subgroups across time points, including at PD (Table). Results for D + T vs BRAFi alone by LDH in COMBI‐d and COMBI‐v for all EORTC QLQ‐C3cl be presented. (Table presented) Conclusions: D + T consistently improved HRQOL vs BRAFi alone for most EORTC QLQ‐C30 domains, regardless of LDH, further supporting continued use of D + T in BRAF‐mutant melanoma across LDH subgroups. HRQOL benefit with D + T may be greater in pts with LDH > ULN.