Vemurafenib monotherapy has potential for BRAF-mutated NSCLC
medwireNews: Single-agent vemurafenib has demonstrated promising antitumor activity against non-small-cell lung cancer (NSCLC) harboring BRAF V600E mutations in the VE-BASKET trial.
Treatment with the BRAF inhibitor given at a twice daily dose of 960 mg led to an objective response rate (ORR) of 37.1% among the 62 participants of the NSCLC cohort of the phase II study, all of whom had the BRAF V600E mutation except one individual with an unspecified V600 variant. All responses were partial and lasted for a median of 7.2 months. The clinical benefit rate (CBR) – which additionally included patients who achieved stable disease for at least 6 months – was 48.4%.
The ORR was comparable for the 54 individuals who had previously received a median of two systemic regimens and the eight who were treatment-naïve, at 37.0% and 37.5%, respectively, but the CBR was lower among previously treated than untreated patients, at 46.3% versus 62.5%.
Over a median follow-up of 10.7 months, median overall survival (OS) and progression-free survival (PFS) times were 15.4 and 6.5 months, respectively, in the full cohort. The corresponding durations for the previously treated group were 15.4 and 6.1 months, while median OS was unreached and median PFS was 12.9 months in the treatment-naïve group.
These differences “may be explained either by small patient numbers or by increased acquisition of resistance mechanisms with prior therapy,” which suggests the potential benefit of using targeted therapy earlier in the course of treatment, writes the team.
Vivek Subbiah, from The University of Texas MD Anderson Cancer Center in Houston, USA, and co-investigators note that “[t]he safety profile of vemurafenib was similar to that observed in melanoma studies,” with no new safety signals.
Seventy-seven percent of participants experienced an adverse event (AE) of grade 3 or 4, most commonly anemia (10%), dyspnea (8%), and decreased appetite (8%), and there were two grade 5 events, but neither of these was considered related to vemurafenib.
Treatment was interrupted in 40% of patients, while 61% needed a dose reduction and six discontinued treatment due to AEs, according to the article published in JCO Precision Oncology.
Noting that the combination of dabrafenib and trametinib has been approved in Europe and the USA for individuals with BRAF V600E mutation-positive NSCLC, the researchers say “combination therapy consisting of a BRAF inhibitor and an MEK inhibitor has now become standard of care” for these patients.
But they believe that the current results point to “a role for single-agent BRAF inhibition in patients with NSCLC and BRAF V600 mutations.”
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