KEY TAKEAWAYS
- Phase II BRAF V600E trial evaluated the efficacy and safety of the combination of Dabrafenib (D) and Trametinib (T) in pretreated and treatment-naïve patients with mNSCLC carrying the BRAF V600E mutation.
- The study used a multicenter, open-label design with 36 treatment-naïve and 57 pretreated patients receiving D 150 mg twice daily and T 2 mg daily.
- The updated analysis showed a median follow-up of 16.3 months with a median OS of 17.3 months (95% CI: 12.3, 40.2; 3-year OS: 40%) and 18.2 months (95% CI: 14.3, 28.6; 3-year OS: 33%) for treatment-naïve and pretreated patients, respectively.
- The safety profile of the D+T combination was similar to previously reported results. Further validation is ongoing to corroborate current genomic findings.
Patients with BRAF V600E mut metastatic NSCLC who had previously been treated (cohort B) or were treatment-naive (cohort C) were enrolled in phase II multicenter, open-label study to assess the efficacy and safety of D+T. The findings from the initial study have been shared. The survival and genomic analysis data for Cohorts B and C have been updated and are presented in this study. Pretreated (n=57) and treatment-naive (n=36) patients were given D 150 mg twice daily and T 2 mg once daily. The overall response rate is the primary goal, and the other objectives for D+T are secondary. Central tumor testing was performed with an NGS cancer-targeted panel (Oncomine Dx Target test, ThermoFisher Scientific). Potential associations between the pretreatment genomic landscape and the posttreatment efficacy endpoints were analyzed using KM curves and Cox regression models.
Median (m) follow-up for tx-naive patients as of June 22, 2019, was 16.3 months, and for pretreated patients, 16.6 months. 3-year overall survival rate was 40% among tx-naive patients and 33% among pretreated patients. Median overall survival (mOS) was 17.3 months among tx-naive patients and 18.2 months among pretreated patients. Central confirmation of BRAF V600E mut in 57/62 tumor samples from 93 patients; c-MET T1010I, KRAS G12V, ALK fusion, and 2 JAK3 S493C positivity in 5 non-confirmed BRAF tumors (3 patients with PR; median progression-free survival [mPFS]: 13.8 months; overall survival [OS]: not estimable [NE] due to small sample size. Concomitant somatic mutations and/or genetic alterations were found in 11 patients (18%), including BRAF G466V, KRAS G13C, cMET exon 14 skippings, and PI3K pathway alterations in four patients. Patients (Pts) whose tumors also had concurrent genetic alterations, especially in the PI3K pathway IDH1 R132X, tended to have shorter PFS and OS. The safety profile was consistent with earlier findings. Improved and long-lasting OS rates with combination D+T in BRAF V600E mut NSCLC pts were reported in this update of the BRF113928 study. The clinical outcomes of such patients could be affected by comorbid genetic alterations. The current genomic findings are being validated further to ensure their accuracy.
Source:https://meetings.asco.org/abstracts-presentations/184921
Clinical Trial: https://clinicaltrials.gov/ct2/show/NCT01336634
David Planchard, Benjamin Besse, Harry Groen, Sayed MS Hashemi, Julien Mazieres, Tae Min Kim, Elisabeth A. Quoix, Pierre Jean Souquet, Fabrice Barlesi, Christina S Baik, Liza C Villaruz, Ronan Joseph Kelly, Shirong Zhang, Monique Tan, Eduard Gasal, Libero Santarpia, Bruce E. Johnson/ 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)/J Clin Oncol 38: 2020 (suppl; abstr 9593) DOI10.1200/JCO.2020.38.15_suppl.9593
