Clinical outcomes with frontline immunotherapy (IO) in BRAF-mutant NSCLC.

Abstract

e21089 Background: Oncogenic BRAF mutations are present in approximately 4% of non-small cell lung cancers (NSCLC). They are categorized as class I, II, or III according to their effect on the MAPK pathway. Little is known about how oncogenic BRAF mutations influence tumor PD-L1 expression and response to IO. We evaluated the clinical outcomes of frontline IO among BRAF classes. Methods: We performed a retrospective analysis of patients with BR AF-mutant NSCLC from January 1, 2012 through March 30, 2020. BRAF mutations were detected using next-generation sequencing or genotyping methods. PD-L1 expression was assessed using 22C3 or SP263 assays. Patient demographics were collected through electronic medical records review. In those with advanced/metastatic disease, we captured response to anticancer therapies using standardized real-world (rw) criteria and calculated rwOS using Kaplan-Meier method with log-rank test. Results: Of all 9,004 lung cancer patients (all histologies) with genotyping testing, 79 had NSCLC and an oncogenic BRAF mutation. 52% were females, 95% had adenocarcinoma, 81% were active/former smokers, and 76% had PD-L1 ≥1%. 39 patients had class I, 24 had class II, and 16 had class III mutations. Of these, 43 patients had advanced/metastatic disease evaluable for response. Patients with class I mutations who received first-line IO trended towards improved rwOS (42.6 months) vs. frontline anti-BRAF therapy (22.7 months; p= 0.51) and chemotherapy (19.6 months; p= 0.63). Patients with non-class I mutations, also trended towards improved rwOS with frontline IO (18.8 months) compared to frontline chemotherapy (9.9 months; p= 0.25). Outcomes were better in all patients with PD-L1 levels ≥1% and ≥50% who received IO. Patients with non-class I variants tended to have shorter rwOS with IO or chemotherapy compared to those with class I mutations (Table 1). Despite an overall trend towards improved outcomes with first-line IO, results did not reach significance likely due to the limited number of evaluable patients. Conclusions: The use of frontline IO may be associated with better outcomes than frontline chemotherapy or targeted therapies in patients with BRAF-mutant NSCLC. Patients with class I mutations and/or higher tumor PD-L1 expression seem to derive the most benefit. [Table: see text]