Supporting Authors: Axel Hauschild, Mario Santinami, Victoria Atkinson, Mario Mandalà, Vanna Chiarion-Sileni, Marta Nyakas, Caroline Dutriaux, Andrew Haydon, Laurent Mortier, Caroline Robert, Jacob Schachter, Dirk Schadendorf, Ran Ji, Paola Aimone, Bijoyesh Mookerjee, Richard Kefford, Reinhard Dummer, John M. Kirkwood, Georgina V. Long
Background: The COMBI-AD trial demonstrated that adjuvant treatment with dabrafenib + trametinib (D+T) in patients (pts) with resected stage III BRAF-mutant melanoma significantly reduced the risk of melanoma recurrence vs placebo (PBO). Pts were stratified based on the AJCC 7 disease stage classification.
Objectives: To analyze and present the efficacy results from the COMBI-AD study based on updated AJCC 8 staging classification.
Methods: COMBI-AD is a randomized, double-blind, PBO-controlled, phase 3 study evaluating pts with stage III BRAF V600E/K–mutant melanoma without prior anticancer therapy. Pts were randomized 1:1 within 12 weeks of complete resection to receive D 150 mg twice daily plus T 2 mg once daily or matching PBOs for 12 months. The primary end point was relapse-free survival (RFS). Pts were stratified by disease stage (stages IIIA, IIIB, and IIIC) based on AJCC 7 criteria. This post hoc subgroup analysis evaluated RFS in pts by disease stage based on AJCC 8 (stages IIIA, IIIB, IIIC, and IIID).
Results: 870 pts were randomized (D+T, n = 438; PBO, n = 432). Pts were recategorized per AJCC 8 into stages IIIA (D+T, n = 50; PBO, n = 39), IIIB (D+T, n = 145; PBO, n = 154), IIIC (D+T, n = 217; PBO, n = 214), and IIID (D+T, n = 22; PBO, n = 17). RFS benefit with D+T over PBO was observed regardless of disease stage (stage IIIA: HR 0.46 [95% CI, 0.17-1.21]; stage IIIB: HR 0.46 [95% CI, 0.33-0.65]; stage IIIC: HR 0.49 [95% CI, 0.38-0.64]), with the largest benefit observed in higher-risk stage IIID pts (HR 0.34 [95% CI, 0.15-0.80]). When stage IIIB and IIIC subgroups were combined, the HR for RFS (D+T vs PBO) was the same (0.48) regardless of the AJCC classification used. Three-year RFS rates favored pts in the D+T vs PBO arm across all disease stages: IIIA, 83% vs 70%; IIIB, 63% vs 43%; IIIC, 52% vs 33%; and IIID, 40% vs 18%. RFS rates were similar in D+T and PBO arms in pts with stages IIIA, IIIB, and IIIC disease whether classified by AJCC 7th or 8th edition melanoma staging system.
Conclusions: The RFS benefit observed with D+T vs PBO in pts with resected BRAF V600E/K–mutant melanoma was similar across all stages and was maintained when reclassified by AJCC 8 compared with the original AJCC 7 classification.
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.
