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Brigatinib confers durable PFS benefit in ALK-positive NSCLC
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Brigatinib conferred a durable PFS benefit compared with crizotinib among patients with ALK-positive non-small cell lung cancer who had not received prior ALK inhibitor therapy, according to updated results of the phase 3 ALTA-1L trial presented at ESMO Asia Congress.
“Given the complexity of this disease and the expected longevity of the population, it is important for physicians to have multiple well-tolerated and durable treatment options to address the needs of their patients,” investigator D. Ross Camidge, MD, PhD, Joyce Zeff chair in lung cancer research at University of Colorado Cancer Center, said in a press release. “With 25 months of follow up from the ALTA-1L trial, brigatinib continues to demonstrate overall and intracranial effectiveness, while also significantly improving quality of life compared to crizotinib, reinforcing its potential as a first-line therapy for ALK-positive NSCLC.”
The trial compared the next-generation ALK inhibitor brigatinib (Alunbrig, Ariad/Takeda) with crizotinib (Xalkori, Pfizer), the first licensed ALK inhibitor crizotinib, among 275 treatment-naive patients with advanced ALK-positive, ALK inhibitor-naive NSCLC.
All patients had ECOG performance status of 0 to 2. Eligible patients had up to one line of prior chemotherapy for advanced NSCLC, and those with asymptomatic central nervous system metastases were allowed to enroll.
Camidge and colleagues assigned 137 patients (median age 58 years) to brigatinib dosed at 180 mg once daily, with a 7-day lead-in period at 90 mg. The other 138 patients (median age, 60 years) received crizotinib dosed at 250 mg twice daily. Patients assigned crizotinib were offered brigatinib upon disease progression.
Comparable percentages of patients in the brigatinib and crizotinib groups received prior chemotherapy (26% vs. 27%) and had brain metastases at baseline (29% vs. 30%).
PFS as assessed by blinded independent review committee served as the primary endpoint. Secondary endpoints included confirmed objective response rate, confirmed intracranial ORR, confirmed intracranial PFS by blinded review, OS and safety.
The first preplanned analysis — based on median follow-up of 11 months in the brigatinib arm and 9.3 months in the crizotinib arm — showed a significantly higher PFS rate for brigatinib-treated patients (67% vs. 43%; HR = 0.49; 95% CI, 0.33-0.74).
At ESMO Asia, Camidge and colleagues presented data based on median follow-up of 24.9 months in the brigatinib group and 15.2 months in the crizotinib group.
Results showed a significantly higher confirmed ORR (74% vs. 62%; P = .0342) and longer median duration of response (not estimable vs. 14 months) in the brigatinib group.
Researchers reported median PFS by blinded independent review of 24 months with brigatinib and 11 months with crizotinib (HR = 0.49; 95% CI, 0.35-0.68). Investigator-assessed PFS showed an even greater benefit with brigatinib (median, 29.4 months vs. 9.2 months; HR = 0.43; 95% CI, 0.31-0.61).
Forty patients assigned brigatinib and 41 assigned crizotinib had brain metastases at baseline. In this group, researchers reported significant benefits with brigatinib with regard to PFS (HR = 0.25; 95% CI, 0.14-0.46) and intracranial PFS (HR = 0.31; 95% CI, 0.17-0.56).
OS data remained immature at data cutoff.
The most common grade 3 or higher treatment-emergent adverse events observed among brigatinib-treated patients included increased creatine phosphokinase (24.3%), increased lipase levels (14%), hypertension (11.8%). The most common grade 3 or higher treatment-emergent adverse events in the crizotinib group included increased alanine aminotransferase (10.2%), increased aspartate aminotransferase (6.6%) and increased lipase levels (6.6%).
Patients assigned brigatinib appeared more than twice as likely to develop any-grade interstitial lung disease or pneumonitis (5.1% vs. 2.2%). They also were more likely to discontinue treatment due to adverse events (12.5% vs. 8.8%).
Reference:
Camidge R, et al. Abstract LBA1. Presented at ESMO Asia; Nov. 22-24, 2019; Singapore.
Disclosure: Ariad Pharmaceuticals provided funding for this study. Camidge reports research funding from Takeda, as well as honoraria from Arrys Therapeutics/Kyn Therapeutics, AztraZeneca, Biothera Pharmaceuticals, Celgene, Clovis Oncology, Daiichi Sankyo, G1 Therapeutics, Genentech/Roche, Genoptix, Ignyta, Lycera, Mersana Therapeutics, Novartis, Orion, Revolution Medicines and Takeda.