Impact of prior chemotherapy (CT) on dabrafenib plus trametinib (D + T) outcomes in <i>BRAF</i> ^V600E –mutated metastatic non–small cell lung cancer (NSCLC): A post hoc analysis.

Abstract

e20666 Background: The Phase II study (NCT01336634) evaluated the BRAF inhibitor, dabrafenib with the MEK inhibitor, trametinib, in patients with BRAF V600E–mutant metastatic stage IV NSCLC. In this exploratory post hoc analysis, we examined outcomes according to the duration of prior CT exposure before D + T initiation. Methods: This post hoc analysis included adult patients with metastatic stage IV, BRAF V600E–mutated NSCLC from sub-cohort B in the NCT01336634 study who received D + T as second-line therapy after prior systemic CT. Patients were further stratified by duration of prior CT exposure (≤4 weeks vs &gt;4 weeks). Dabrafenib 150 mg twice daily and trametinib 2 mg once daily were administered orally. Progression-free survival (PFS) and overall survival (OS) were estimated using Kaplan–Meier methods and compared descriptively. PFS and OS were calculated from the date of D + T initiation (day 1). Results: A total of 38 patients received D + T as second-line therapy in sub-cohort B. The mean duration of prior CT was 3.0 months (SD = 4.0, n = 37), with a median of 2.1 months (Q1–Q3: 0.8–2.8; range: 0.0–21.4). Overall, 11 patients (28.9%) had ≤4-weeks of prior CT, and 26 (68.4%) had &gt;4 weeks; data was missing for 1 patient. In patients who received ≤4 weeks of prior CT before starting D + T had numerically longer PFS than those with &gt;4 weeks, by both investigator assessment (median PFS 19.3 vs 9.7 months, p = 0.101; PFS events: 7 vs 23) and independent review (58.1 vs 7.7 months, p = 0.123; PFS events: 6 vs 23). A numerically longer median OS was also observed in the ≤4-week group compared with the &gt;4-week group (55.2 vs 19.2 months, p = 0.388; OS events: 8 vs 21). Median follow-up was 18.2 months overall, 55.2 months in the ≤4-week subgroup, and 17.0 months in the &gt;4-week subgroup. Conclusions: This exploratory, hypothesis-generating analysis suggests that, in patients with BRAF V600E–mutated metastatic NSCLC treated with second-line D + T, shorter prior CT exposure (≤4 weeks) was associated with a trend toward numerically longer PFS and OS compared with longer exposure (&gt;4 weeks). These findings, derived from a small sample size, post hoc design, and limited number of events, support further evaluation in prospective studies. Future analyses using start of prior CT as time zero may help assess potential lead-time effects. Clinical trial information: NCT01336634 .