Background: Combination TT, dabrafenib/trametinib (D+T) or vemurafenib/cobimetinib (V+C) and combination I-O (ipilimumab/nivolumab [I+N]) or PDL1 monotherapy (nivolumab [N] or pembrolizumab [P]) are approved for the treatment of BRAF+ MM. Without head to head trials comparing TT and I-O comparative effectiveness of real world clinical outcomes may better inform treatment decisions. Methods: Physicians from the Cardinal Health Oncology Provider Extended Network identified BRAF+ MM patients initiating 1L with D+T, I+N, N or P after 01/01/2014 through 6/31/2017. Treatment and clinical data (including target lesion measurements) were entered into electronic case-report forms which were validated by clinical research staff. 1L ORR using RECIST v1.1 and TTF was compared between TT and I-O. Odds ratio (OR) for objective response (complete or partial) using multivariate logistic regression models and hazard ratio (HR) for TTF using a Cox proportional hazards model adjusted for patient characteristics was calculated. Results: 53 providers contributed 440 patients: TT = 283 (D+T = 188, V+C = 95), I-O = 157 (I+N = 86, N or P = 71). Patient characteristics, ORR, median TTF, and model estimates are in the table. ORR was significantly higher in TT v I-O (60.1% v 45.9%, p < 0.01); adjusted odds of objective response 42% less for I-O (OR = 0.58). Median TTF: TT = 11.4 v I-O = 7.1 (p < 0.001); adjusted risk of treatment failure increased by 64% for I-O treated compared to TT: HR: 1.64; 95% CI: 1.25-2.14, p < 0.001. Conclusions: In the largest community-based study of 1L outcomes for BRAF+ MM ORR was significantly higher for TT (unadjusted and adjusted) and TTF longer for TT v I-O. We observe an apparent preference for TT in the community in higher risk patients (liver metastases and LDH value).

* p < 0.05