Abstract A083: BRAF Inhibitors in BRAF V600E-Mutated Solid Tumors: A Real World Single Center Experience Post-Tumor-Agnostic FDA Approval

Abstract Background: The 2022 FDA tumor-agnostic approval of dabrafenib plus trametinib expanded targeted therapy for BRAF V600E-mutated unresectable or metastatic solid tumors beyond traditional indications. However, real-world evidence, especially in diverse histologies such as CNS, lung, and non-CRC GI cancers, remains limited. Methods: We conducted a retrospective review of patients with BRAF V600E-mutated cancers treated with BRAF inhibitors (BRAFi, often combined with MEK or EGFR inhibitors) at a large academic hospital from 2013 to 2025. Key data collected included demographics, treatment line and duration, radiographic responses (complete response [CR], partial response [PR], stable disease, or progression of disease [POD]), and progression-free survival (PFS, defined as time from BRAFi start to POD or death). We calculated objective response rate (ORR = CR + PR), disease control rate (DCR = ORR + stable disease), and median PFS, both overall and by histology: CNS tumors, lung cancers, GI malignancies (pancreas, sinonasal, neuroendocrine), and colorectal cancer (CRC). Results: Among 30 patients (CNS, n=3; lung, n=7; non-CRC GI, n=3; CRC, n=17), median age was 69 years (range 5-81), with 63% female, 57% deceased, and median BRAFi treatment line of 2 (range 1-5). Regimens primarily involved encorafenib-based combinations (50%) or dabrafenib/trametinib (40%). Overall, ORR was 20%, DCR 57%, median treatment duration 7.5 months, and median PFS 6.9 months (63% events). By histology, outcomes varied markedly: CNS showed robust activity (ORR 67%, DCR 100%, median PFS 22.8 months), suggesting durable BRAF targeting in brain tumors; lung demonstrated moderate efficacy (ORR 43%, DCR 71%, median PFS 10.8 months), indicating potential early-line benefits; non-CRC GI cancers exhibited poor responses (ORR 0%, DCR 0%, median PFS 4.6 months), highlighting limited utility; and CRC had modest control (ORR 6%, DCR 53%, median PFS 6.5 months), reflecting partial synergies with EGFR inhibitors but frequent resistance. Conclusions: This real-world series reveals histology-dependent BRAFi efficacy post-tumor-agnostic approval, with encouraging and prolonged PFS in CNS and lung tumors—potentially guiding expanded use in these contexts - but suboptimal outcomes in GI and CRC, underscoring possible resistance mechanisms and the value of biomarker-driven selection. These insights advocate for larger, prospective registries to refine precision oncology strategies. Citation Format: Sharon Santhosh, Srinivas Govindan, Adit Singhal, Aaron Goldstein, Jervon Wright, Xinhua Zhu. BRAF Inhibitors in BRAF V600E-Mutated Solid Tumors: A Real World Single Center Experience Post-Tumor-Agnostic FDA Approval [abstract]. In: Proceedings of the AACR-NCI-EORTC International Conference on Molecular Targets and Cancer Therapeutics; 2025 Oct 22-26; Boston, MA. Philadelphia (PA): AACR; Mol Cancer Ther 2025;24(10 Suppl):Abstract nr A083.