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DNA assay confirms response, activity with brigatinib in ALK-positive non–small cell lung cancer
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CHICAGO — Brigatinib led to substantial activity in patients with ALK-positive, crizotinib-refractory non–small cell lung cancer, according to results presented at the ASCO Annual Meeting.
The results also demonstrated that ALK fusions were detected in approximately half of the plasma samples collected from the patient population.
“[We] looked at the ability of cell-free DNA assay ... to predict which patients with ALK-fused, crizotinib-resistant disease [would] respond to brigatinib,” Lyudmila A. Bazhenova, MD, a medical oncologist at UC San Diego Health, told HemOnc Today. “We also set to discover if there is a uniformed mechanism of resistance to brigatinib.”
The FDA granted accelerated approval to brigatinib (Alunbrig, Ariad) — a next-generation anaplastic lymphoma kinase (ALK) inhibitor — in April for the treatment of patients with metastatic ALK–positive NSCLC who progressed on or are intolerant to crizotinib (Xalkori; Pfizer, EMD Serono) based on tumor response rate and duration of response data from the ALTA trial. The FDA recommended a dose of 90 mg brigatinib orally once daily for the first 7 days, followed by an increased dose of 180 mg orally once daily, if well tolerated.
Bazhenova and colleagues collected plasma samples from 291 patients with ALK-positive, crizotinib-resistant NSCLC enrolled in both a phase 1/2 (N = 69) and phase 2 ALTA (N = 222) trial.
The researchers aimed to analyze the association between brigatinib efficacy and ALK mutation status using the samples from the baseline to the end of brigatinib treatment in the patient population.
Evaluable plasma samples were collected at baseline from 67 patients who had a confirmed objective response rate of 49% to brigatinib.
The researchers detected an ALK fusion in the plasma of 45% of the evaluable patients. Among that patient population, 33% had a secondary ALK mutation and 67% did not.
Two patients with secondary ALK mutations had a complete response and three patients had a partial response to therapy.
Thirty-five patients discontinued brigatinib, of whom 20 had evaluable samples collected at end of therapy. The researchers detected no new mutations at end of therapy in 75% of the patients who discontinued therapy and had evaluable samples.
“Patients with ALK secondary resistant mutations identified [with cell-free DNA assay], and without ... respond to brigatinib equally well,” she said. “There is no uniform resistance mechanism in post brigatinib patients. The results of this abstract confirm results of the tissue biopsy abstract reported at [last year’s] ASCO by the same group of authors.” – by Ryan McDonald
Reference:
Bazhenova LA, et al. Abstract 9065. Presented at: ASCO Annual Meeting; June 2-6, 2017; Chicago.
Disclosure: The study was sponsored by Ariad Pharmaceuticals. Bazhenova reports serving on a speaker’s bureau and as a consultant or advisor for Pfizer, as well as a consultant or advisor for Ariad Pharmaceuticals. In addition, Bazhenova reports stock and other ownership interests in Epic Sciences. Please see the full study for a list of all other relevant financial disclosures.