Treatment with dabrafenib and trametinib produced similar benefits in pretreated and treatment-naïve patients.
Updated survival and genomic analysis data from a multicenter, open-label phase 2 study (BRF113928) were presented at the 2020 ASCO Virtual Scientific Program. The study evaluated the safety and efficacy of dabrafenib + trametinib in pretreated patients (cohort B) and treatment-naïve patients (cohort C) with BRAF V600E–mutant, metastatic non–small-cell lung cancer (NSCLC); the results of the initial primary analysis were previously reported.
Thirty-six treatment-naïve patients and 57 pretreated patients were given 150 mg dabrafenib twice daily and 2 mg trametinib once daily. The primary end point was overall response rate; secondary end points were progression-free survival (PFS), duration of response, overall survival (OS), safety, tolerability, and pharmacokinetics of dabrafenib and trametinib. The next-generation sequencing Oncomine Dx Target Test was used to sequence tumor samples. To assess the possible associations between patient efficacy end points and genomic landscape, the researchers used Kaplan-Meier curves and Cox regression models.
As of June 22, 2019, the treatment-naïve patients had a median follow-up of 16.3 months and a median OS of 17.3 months (95% confidence interval [CI], 12.3-40.2; 3-year OS, 40%); 14 of 36 patients were still alive. The pretreated patients had a median follow-up of 16.6 months and a median OS of 18.2 months (95% CI, 14.3-28.6; 3-year OS, 33%); 11 of 57 patients were still alive.
Among 62 tumor samples from 93 patients, 57 had confirmed BRAF V600E mutation. Of the 5 nonconfirmed BRAF tumor samples, 2 had JAK3 S493C mutations, 1 had a c-MET T1010I mutation, 1 had a KRAS G12V mutation, and 1 had an ALK fusion, with a median PFS of 13.8 months and an OS that was not estimable because of limited data. There were 11 BRAF V600E–mutant patients with concomitant somatic mutations and/or genetic alterations: 4 patients had mutations in the PI3K pathway, 4 patients had mutations at IDH1 R132X, 1 patient had a BRAF G466V mutation, 1 patient had a KRAS G13C mutation, and 1 patient had a c-MET exon 14 skipping mutation. Patients with these concomitant mutations, especially PI3K pathway mutations, had a trend of decreased PFS and OS. The safety profile showed similar results to the previous report.
The authors concluded that dabrafenib + trametinib treatment improves OS in patients with BRAF V600E–mutant NSCLC, and noted that concomitant genetic mutations can influence clinical outcomes in these patients. Additional analysis of genomic data is ongoing.
|N = 36|
|ORR, n (%)a||23 (63.9)||39 (68.4)|
|OS rates, % (95% CI)|
|12-month||74 (55-85)||66 (52-77)|
|24-month||49 (32-65)||41 (28-53)|
|36-month||40 (24-56)||33 (21-46)|
|48-month||NA (NA)||26 (15-38)|
CI indicates confidence interval; mDOR, median duration of response; mOS, median overall survival; mPFS, median progression-free survival; NA, not applicable; ORR, overall response rate; OS, overall survival.
Planchard D, et al. J Clin Oncol. 2020;38(suppl 15):Abstract 9593.