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First-line brigatinib improves PFS for ALK-positive non-small cell lung cancer
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First-line therapy with brigatinib significantly improved PFS compared with crizotinib among treatment-naive patients with advanced ALK-positive non-small cell lung cancer, according to results of the global, randomized phase 3 ALTA-1L trial presented at International Association for the Study of Lung Cancer’s World Conference on Lung Cancer.
The trial — stopped after a planned interim analysis — compared the next-generation ALK inhibitor brigatinib (Alunbrig; Takeda Oncology, Ariad) with the first licensed ALK inhibitor crizotinib (Xalkori; Pfizer, EMD Serono) among 275 treatment-naive patients with advanced ALK-positive NSCLC.
D. Ross Camidge, MD, PhD, director of thoracic oncology at University of Colorado, and colleagues assigned 137 patients to 180 mg once-daily brigatinib (7-day lead-in period at 90 mg) and 138 patients to 250 mg twice-daily crizotinib.
PFS served as the primary endpoint. Secondary endpoints included objective response rate and intracranial response.
The first interim analysis was planned when approximately half of 198 expected disease-progression events or deaths occurred.
Median follow-up was 11 months in the brigatinib arm and 9.3 months in the crizotinib arm.
The results — published simultaneously in The New England Journal of Medicine — showed a significantly higher PFS rate for brigatinib compared with crizotinib (67% vs. 43%; HR for disease progression or death = 0.49; 95% CI, 0.33-0.74).
The ORR was 71% (95% CI, 62-78) with brigatinib and 60% (95% CI, 51-68) with crizotinib.
Among patients with measurable lesions, the researchers observed an intracranial response rate of 78% (95% CI, 52-94) among those treated with brigatinib compared with 29% (95% CI, 11-52) with crizotinib.
The researchers observed no new safety concerns.
“Interim data show brigatinib is set to become a first-line treatment option for ALK-positive lung cancer,” Camidge said in a press release. “Even with only 9 to 11 months of follow-up, the efficacy of brigatinib is clearly superior to crizotinib. A lot of the initial difference is driven by an effect on brain metastases, which tend to be an earlier progression event. However, once differences in control of disease outside the brain have time to manifest, it is possible the PFS improvement may increase.” – by Jennifer Southall
References:
Camidge DR, et al. Abstract PL02.03. Presented at: International Association for the Study of Lung Cancer’s World Conference on Lung Cancer; Sept. 23-26, 2018; Toronto, Canada.
Camidge DR, et al. N Eng J Med. 2018;doi:10.1056/NEJMoa1810171.
Disclosures: Camidge reports nonfinancial support from Millennium Pharmaceuticals during the conduct of the study, and grants or personal fees from Arrys/Kyn, AstraZeneca, Bio-Thera, Celgene, Clovis, Daichii Sankyo, G1 Therapeutics, Genoptix, Hansoh, Ignyta, Lycera, Mersana Therapeutics, Novartis, Orion, Revolution Med, Roche/Genentech, Takeda outside the submitted work. Please see the study for all other authors’ relevant financial disclosures.