Characteristics of Patients with a Complete Response Treated with Dabrafenib plus Trametinib Combination Therapy: Findings from Pooled COMBI-d and COMBI-v 5-Year Analysis

Background: Two large phase 3 studies (COMBI-d [NCT01584648] and COMBI-v [NCT01597908]) evaluated the efficacy and safety of oral dabrafenib 150 mg twice daily plus trametinib 2 mg once daily (D+T) as first-line therapy in patients (pts) with BRAF V600E- or V600K-mutant unresectable or metastatic cutaneous melanoma.

Objectives: To further characterize pts most likely to benefit from D+T by analyzing data at 5 years of follow-up.

Methods: A recent 5-year analysis of D+T using pooled data from COMBI-d and COMBI-v was conducted. To further characterize pts most likely to benefit from D+T, we analyzed outcomes and clinical features of pts with a confirmed complete response (CR) in this data set.

Results: Pts with confirmed CR (n = 109 [19%]) had favorable outcomes (5-year progression-free survival [PFS], 49%; 5-year overall survival [OS], 71%) versus the overall population (N = 563; 5-year PFS, 19%; 5-year OS, 34%). Median duration of CR was 36.7 months (95% CI, 24.1-not reached [NR]); 55 of 109 pts with CR (50%) had ongoing CR at the data cutoff (COMBI-d, Dec 10, 2018; COMBI-v, Oct 8, 2018; median follow-up, 64.0 months) or at study withdrawal. Median PFS (54.3 vs 11.1 months) and OS (NR vs 25.9 months) were higher in pts with CR vs the overall population. Pts with CR had favorable baseline prognostic factors compared with the overall population, including normal lactate dehydrogenase levels (90% vs 65%), ECOG performance status of 0 (86% vs 72%), <3 organ sites with metastases (84% vs 51%), and a lower median sum of target lesions (34 vs 57 mm). Baseline factors such as median age and patient sex were similar between both groups. New lesions in pts with CR who progressed (n = 48) were most commonly reported in the central nervous system (54%), lung (17%), and lymph nodes (17%), which were similar to sites of progression in the overall population. Subsequent therapy was received by 43 pts with CR (39%) and most commonly included immunotherapy (n = 28, 26% [anti–PD-1, n = 21; anti–CTLA-4, n = 17]) and BRAF-targeted therapy (n = 25, 23%).

Conclusions: These results suggest that baseline characteristics may be useful for selecting pts with advanced BRAF V600E/K-mutant melanoma who may derive the greatest clinical benefit from first-line D+T combination therapy. Further validation is warranted.

Notes: COMBI-d and COMBI-v studies were 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 2019 International Congress of the Society for Melanoma Research (SMR). All rights reserved.