From the Journals

Vemurafenib has durable activity in NSCLC harboring BRAF V600 mutations



The oral BRAF(V600E) kinase inhibitor vemurafenib (Zelboraf) has durable activity in non–small cell lung cancer (NSCLC) harboring BRAF V600 mutations and possibly provides greater benefit for treatment-naive patients, found the phase 2, open-label, single-arm VE-BASKET trial.

“Targetable oncogenic drivers in NSCLC with robust clinical validation include EGFR mutations and ALK and ROS1 fusions, but identifying other targetable, clinically important subgroups of NSCLC is a high priority,” wrote the investigators, who were led by Vivek Subbiah, MD, of the University of Texas MD Anderson Cancer Center, Houston. Roughly 1%-4% of NSCLC patients have tumors harboring a BRAF V600 mutation, they noted.

Analyses were based on 62 patients with BRAF V600–mutant NSCLC enrolled in the trial’s NSCLC cohort or all-comers cohort. All received vemurafenib (960 mg twice daily) until disease progression or unacceptable toxicity.

Thirteen percent of the patients had not received any previous systemic therapy. Among those previously treated, the median number of systemic regimens received was two.

Results reported in JCO Precicion Oncology showed that the median treatment duration was 6.0 months for all patients (12.0 months for previously untreated patients and 5.7 months for previously treated patients).

The objective response rate, the trial’s primary endpoint, was 37.1% overall; it was similar in the previously untreated group and the previously treated group (37.5% and 37.0%, respectively). The clinical benefit rate was 48.4% overall, with a larger differential according to previous treatment at 62.5% and 46.3%.

Median progression-free survival was 6.5 months in all patients (12.9 months in those previously untreated and 6.1 months in those previously treated), and median overall survival was 15.4 months in all patients (not estimable in those previously untreated, but 15.4 months in those previously treated).

The most common adverse events of any grade were nausea (seen in 40% of patients), hyperkeratosis (34%), and decreased appetite (32%). The most common grade 3 or worse adverse event was anemia (10%). The safety profile generally resembled that previously observed among patients with melanoma, with no new signals.

“Vemurafenib showed promising activity in patients with NSCLC harboring BRAF V600 mutations,” Dr. Subbiah and colleagues concluded. “The prolonged [overall survival] … in the NSCLC population represents promising durability of effect with single-agent BRAF inhibition.”

“The apparent increase in median [progression-free survival] in previously untreated patients compared with previously treated patients warrants additional investigation of earlier treatment in this patient population,” they maintained.

Dr. Subbiah disclosed having a consulting or advisory role with or receiving research funding from numerous pharmaceutical companies. The study was sponsored by Hoffmann-La Roche.

SOURCE: Subbiah V et al. JCO Precis Oncol. 2019 June 27. doi: 10.1200/PO.18.00266.

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