Systematic review and indirect treatment comparison (ITC) of dabrafenib (Dab) and trametinib (Tram) versus first-line (1L) treatments for metastatic melanoma (MM).

Abstract

e20012 Background: In PhIII randomized controlled trials (RCTs), Dab and Tram have shown significant improvement in the primary endpoint of progression-free survival (PFS) as monotherapies vs dacarbazine (DTIC) in 1L patients (pts) with BRAF V600E+ MM. Overall survival (OS) in these studies was confounded by crossover of DTIC pts to active treatment (trt) upon disease progression. This study compares PFS and OS for Dab and Tram with other 1L MM trts. Methods: Embase, MEDLINE, CCTR, and conferences were systematically searched through 10/2012 for relevant RCTs. Comparators were DTIC, vemurafenib (Vem), and ipilimumab (Ipi). Using random-effects network meta-analysis, Dab and Tram were compared directly (D) vs DTIC and indirectly (I) vs Vem and DTIC+Ipi. Results: 48 studies (147 publications) met inclusion criteria; 4studies (1,603 pts) contributed data to current network meta-analysis.Both Dab and Tram showed statistically significant reduction in the risk of progression directly vs DTIC and indirectly vs DTIC+Ipi and comparable PFS indirectly vs Vem (no statistically significant difference). Dab and Tram also demonstrated a statistically nonsignificant but numerically lower hazard of death directly vs DTIC and indirectly vs Vem and DTIC+Ipi. Conclusions: Using ITC, 1L trt of MM with Dab and Tram monotherapies was statistically significantly better than DTIC and DTIC+Ipi for PFS, with comparable efficacy to Vem for PFS and OS. Results must be interpreted cautiously given methodological assumptions and immature OS data for Dab and Tram. H2H studies remain gold standard for comparing trts. [Table: see text]