Retrospective study of BRAF inhibitor-based therapy in patients with BRAF mutated advanced solid tumors (RBAST study).

Abstract

e23265 Background: BRAF mutations are frequently found in melanoma, non-small cell lung cancer (NSCLC), thyroid cancer, to a lesser degree in other tumor types. These mutations constantly activate the kinase domain and result in MAPK pathway hyperactivation. Successful inhibition of this pathway with BRAF/MEK inhibitors (BRAFi/MEKi) results in a clinically meaningful benefit for some patients. The RBAST study, to assess the efficacy and survival outcomes of BRAF inhibitor-based therapy were investigated in patients with solid tumors harboring BRAF mutations. Methods: Data was collected on a total of 697 cases of solid tumor throughout China between Sep 2018 and Dec 2023. Next Generation Sequencing (NGS) is based on the sequencing of tissue samples. Among the samples, the primary endpoints of this study were objective response rate (ORR), disease control rate (DCR), progress-free survival (PFS) and overall survival (OS). The impact of co-mutations with other genes and BRAF variant allele frequency on treatment efficacy was also assessed in this study. Results: BRAF mutations were detected in 36 cases and 15 patients received BRAFi based therapy were identified. For patients who received BRAFi therapy, the best ORR was 26.7% with 4 patients recorded partial response (PR). There were 2 patients with progressive disease giving a DCR of 86.7%. Responses were observed in 4 types of tumors. PR was observed in patients with colorectal cancer (CRC) and melanoma. Median PFS (mPFS) and median OS (mOS) of these patients were 6.0 months (95% CI: 2.3-7.0) and 17.1 months (95% CI: 4.4-NA), respectively. The co-occurring mutation rates of TP53, PTEN, FAT2 and NF1 were 40% (6/15), 20% (3/15), 20% (3/15) and 13.3% (2/15), respectively. No significant difference (p>0.05) in PFS and OS was observed in any co-occurrence of mutations. BRAF mutation variant allele frequency is not an independent prognostic factor for survival with patients received BRAF inhibitor treatment (p>0.05). Conclusions: To the best of our knowledge, this is the first retrospective study exploring BRAFi treatment effectiveness to BRAF mutated solid tumors for Chinese patients. Treatment with BRAF inhibitors is effective for BRAF mutated advanced solid tumors with DCR of 86.7%, mPFS of 6.0 months and mOS of 17.1 months. Co-mutations with other genes and BRAF variant allele frequency did not impact survival outcomes.