Patients with ALK-positive non-small cell lung cancer (NSCLC) whose disease has progressed while on crizotinib (CRZ) may experience improved response rates when treated with the investigational tyrosine kinase inhibitor brigatinib, according to results presented at the 2016 American Society of Clinical Oncology Annual Meeting (June 3-7; Chicago, IL).
Patients with ALK-positive NSCLC treated with CRZ often experience disease progression due to acquired ALK resistant mutations or poor central nervous system drug penetration. In a phase II clinical trial led by Dong-Wan Kim, MD, PhD, of Seoul National University Hospital in South Korea, investigators assessed how objective response rate changed when patients were treated with different doses of brigatinib, a newly developed treatment for resistant ALK mutations in NSCLC, after progression while on CRZ.
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A total of 222 patients were enrolled in the trial, all of whom were diagnosed with advanced ALK-positive disease that progressed while on CRZ. Patients were randomized to two brigatinib treatment regimens: group A (112 patients) received oral brigatinib 90 mg once per day, and group B (110 patients) received the same dose for 7 days followed by 180 mg once per day.
Objective response rate in group A was 45%, with one patient experiencing a complete response. Patients in group B performed slightly better, with an objective response rate of 54% and four confirmed complete responses. Median progression-free survival was also more than 3 months longer in group B than in group A (12.9 months vs 9.2 months, respectively). In addition, while overall survival had not yet been reached in either group, 1-year overall survival was 80% in the 180-mg dose group and 71% in the group that stayed at 90 mg for the duration of their treatment.
However, those in the higher-dose group did experience a greater frequency of adverse events, with 8% requiring dose reductions and 20% having to discontinue treatment. In group A, only 3% and 7% of patients required dose reductions or the discontinuation of treatment, respectively.
Regardless, investigators concluded that both treatment groups produced significant improvements in response and progression-free survival with tolerable safety profiles. A phase 3 trial analyzing how these same regimens will work in TKI-naïve, advanced ALK-positive NSCLC is planned.
“Brigatinib demonstrated substantial efficacy and an acceptable safety profile in both arms,” said Dr Kim. “A consideration of efficacy outcomes and adverse events supports the choice of the 180-mg regimen in future development. Brigatinib has the potential to be a promising new treatment option for patients with crizotinib-resistant ALK-positive NSCLC.”