Updated overall survival (OS) and genomic analysis from a single-arm phase II study of dabrafenib (D) + trametinib (T) in patients (pts) with BRAF V600E mutant (Mut) metastatic non-small cell lung cancer (NSCLC).
Abstract No : 9593
Abstract Type : Poster Session
Indication : BRAF V600E mutanted NSCLC
Intervention : Dabrafenib (D) + Trametinib (T)
Company : Novartis Pharmaceuticals Corporation
Technology : Small molecule
As of June 22, 2019, median (m) follow-up was 16.3 mo in tx-na¨ıve pts and 16.6 mo in pretreated pts. mOS was 17.3 mo (95% CI: 12.3, 40.2; 3 yr OS: 40%) and 18.2 mo (95% CI: 14.3, 28.6; 3 yr OS: 33%) with 14/36 and 11/57 pts alive in tx na¨ıve and pretreated pts respectively. Detailed efficacy results are presented in table. 57/62 tumor samples retrieved from 93 pts were centrally confirmed to have BRAF V600E mut; 5 non-confirmed BRAF tumors (3 pts had PR) were positive for c-MET T1010I, KRAS G12V, ALK fusion and 2 JAK3 S493C with mPFS of 13.8 mo while OS was NE due to limited data points. Eleven pts (18%) had concomitant somatic mutations and/or genetic alterations in addition to BRAF V600E mut: 4 had alterations within PI3K pathway4 had concomitant mutations at IDH1 R132X, and 3 pts had additional mutations at BRAF G466V, KRAS G13C and a cMET exon 14 skipping, respectively. Pts whose tumors had concomitant genetic alterations, particularly in PI3K pathway, showed a trend towards decreased PFS and OS. Safety profile was similar to previous reported results.
This update of BRF113928 study reported improved and durable OS rates with combination D+T in BRAF V600E mut NSCLC pts. Co-occurring genetic alterations might influence clinical outcomes of such pts. Further validation is ongoing to corroborate current genomic findings.
The combination of dabrafenib and trametinib provided durable clinical benefits with a favourable benefit/ risk ratio for NSCLC patients with BRAF V600E positive mutation.