Evaluating clinical activity of MAPK targeted therapies (TT) in cancer patients (pts) with non-V600 BRAF mutations: A systematic scoping review and meta-analysis.

Abstract

3089 Background: Oncogenic nonV600 BRAF mutations (muts) can be classified according to distinct molecular characteristics. TT strategies for class 2 and 3 BRAF muts have not been established. In recent years there have been numerous reports of clinical activity for various TT in pts with nonV600 muts. We performed a systematic scoping review and meta-analysis to assess treatment outcomes with MAPK TT according to BRAF class, cancer type and TT type. Methods: An extensive literature search was conducted from 2010-20. All studies were independently reviewed and extracted by 2 reviewers and in accordance with PRISMA guidelines. Individual patient level data were collected and analyzed from studies that met the following inclusion criteria: published reports of 1) advanced cancer pts with; 2) class 2 or class 3 nonV600 BRAF muts; 3) who received MAPK TT; 4) with treatment response (TR) data available. Primary outcome was overall TR rate (TRR). To assess differences between groups, odds ratios (OR) were calculated using a multi-level mixed-effects logistic regression model. Results: 15,171 studies were screened and 168 were included for data extraction. We identified 100 studies with a total of 396 pts that met inclusion criteria. There were 17 reports (161 pts) of prospective clinical trials and 83 retrospective studies (235 pts). RECIST criteria were used for TR assessment in 183 (46%) pts. The entire study included 280 pts with class 2 and 116 pts with class 3 BRAF muts. Overall, 111 (28%) pts achieved a TR. TRR according to primary tumor type, BRAF class, and TT type is indicated in Table. TRR was lower in reports of prospective studies compared to retrospective studies (OR 0.14, P = 0.002), and in studies that employed RECIST criteria vs. those that didn’t (OR 0.29, P = 0.044). TRR was higher among pts with class 2 muts vs. those with class 3 muts (OR 2.21, P = 0.042). Conclusions: These data establish that MAPK TT have demonstrated clinical activity in cancers with oncogenic nonV600 mutations, and that BRAF mutation class may dictate responsiveness to different TT strategies. TRR may be over-estimated in the retrospective literature. This analysis will be valuable for molecular tumor boards and to guide future clinical trial design. Prospective clinical trials of TT in this pt population are warranted.[Table: see text]