Abstract
9556 Background: Treatment of BRAFV600-mutated mm with V and C+V has clinical benefit. Prior analyses established PFS/OS prognostic models in pts with mm based on clinical variables. This exploratory analysis evaluated the impact of immune and cell cycle gene signatures (GS) from baseline mm (Wongchenko et al, Pigment Cell Melanoma Res2015;28:822) on survival outcomes and associated prognostic models. Methods: Data from all eligible pts with GS data in the BRIM-2, -3, -7, and coBRIM studies were pooled for analysis. The independent effect of GS on PFS/OS outcomes was tested by multivariate Cox proportional hazards models. Recursive partitioning (RP) for censored response variables in a conditional inference framework was performed in the pooled dataset to model relationships between prespecified covariates, GS, and PFS/OS. Prognostic subgroups identified by the model for all pooled pts were applied to pooled treatment cohorts (dacarbazine [D], V, and C+V). Results: GS data were available for 608 pts across pooled studies. Immune GS was associated with improved survival vs cell cycle for PFS (HR = 0.75, 95% CI 0.62–0.89, P= 0.0015) and OS (HR = 0.74, 95% CI 0.61–0.90, P= 0.0024) in multivariate models. HR point estimates were consistent across treatment cohorts. PFS RP models identified baseline LDH, tumor size, and GS as prognostic factors, giving 4 groups with distinct outcomes. GS was not identified as a prognostic factor in OS RP models. C+V improved PFS/OS outcomes vs V across prognostic subgroups. Immune GS was significantly (one-sided Cochran-Armitage trend test) more prevalent in the favorable prognostic groups previously defined for PFS and OS for the V ( P< 0.0001 for both) and C+V cohorts ( P= 0.0240 and P= 0.0269, respectively), but not the D cohort. Conclusions: PFS/OS was significantly improved for pts with immune GS. RP modeling confirmed the importance of GS as an independent prognostic factor for PFS but not OS. The preferential association of immune GS with favorable prognostic subgroups in the C+V and V but not D cohorts and known effects of MAPK signaling on immune response merit further exploration in prospective studies.
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