|The following article features coverage from the International Association for the Study of Lung Cancer (IASLC) 2018 meeting. Click here to read more of Cancer Therapy Advisor‘s conference coverage.|
It appears that patients have better progression-free survival (PFS) with brigatinib than with crizotinib, although the phase 3 trial has not yet concluded.
In preclinical trials, the tyrosine kinase inhibitor (TKI) brigatinib was shown to inhibit native anaplastic lymphoma kinase (ALK) across a panel of ALK-positive cell lines, suggesting it could be more selective than the TKIs that are currently used for the treatment of patients with ALK-positive non-small cell lung cancer (NSCLC).1
In an abstract presented at the IASLC’s 19th World Conference on Lung Cancer in Toronto, Ontario, Canada, researchers discussed results from a phase 3, randomized, open-label study that compared the efficacy and safety of brigatinib with that of crizotinib in ALK-positive locally advanced or metastatic NSCLC that has not previously been treated with an ALK inhibitor. ALK positivity was assessed using what the researchers of the study called “real-world assays.”2
The study investigators assigned 275 TKI-naive patients to receive either 180 mg once-daily brigatinib with a 7-day lead-in period at 90 mg, or 250 mg twice-daily crizotinib (137 individuals and 138 individuals, respectively). The primary end point was PFS, which was assessed by a blinded independent central review.
The first interim analysis was conducted when half of the 198 expected events of disease progression or death had occurred. At this time, the rate of PFS was higher with brigatinib than with crizotinib (estimated 12-month PFS of 67% compared with 43%). The confirmed objective response rate was 71% with brigatinib and 60% with crizotinib, and the confirmed intracranial response rate was 78% and 29%, respectively. Median follow-up for patients in the brigatinib and crizotinib groups was 11 months and 9.3 months, respectively.
According to an article published in The New England Journal of Medicine in tandem with the presentation, early-onset pulmonary events, such as interstitial lung disease and pneumonitis, were observed in patients treated with brigatinib, but not in those who were administered crizotinib.2
The data prompted the investigators to conclude that in the head-to-head analysis, PFS was longer for patients treated with brigatinib compared with those who were treated with crizotinib. The study, which is estimated to last 5 years, is slated to conclude in 2020. There were no new safety concerns outlined in the abstract.
Brigatinib was granted accelerated approval status on April 28, 2017, based on tumor response rate and duration of response for patients with ALK-positive metastatic NSCLC who have had disease progression on or who are intolerant to crizotinib. It was developed by Takeda’s wholly owned subsidiary ARIAD Pharmaceuticals.
Read more of Cancer Therapy Advisor‘s coverage of the IASLC 2018 meeting by visiting the conference page.
- Zhang S, Anjum R, Squillace R, et al. The potent ALK inhibitor brigatinib (AP26113) overcomes mechanisms of resistance to first- and second-generation ALK inhibitors in preclinical models. Clin Cancer Res. 2016;22(22):5527-5538.
- Camidge DR, Kim HR, Ahn M-J, et al. Brigatinib versus crizotinib in ALK-positive non–small-cell lung cancer [published online on September 25, 2018]. N Engl J Med. doi: 10.1056/NEJMoa1810171