The following is the summary of “Efficacy of Brigatinib in Patients With Advanced ALK-Positive NSCLC Who Progressed on Alectinib or Ceritinib: ALK in Lung Cancer Trial of brigAtinib-2 (ALTA-2)” published in the December 2022 issue of Thoracic oncology by Ou, et al.
Brigatinib is an extremely effective next-generation ALK tyrosine kinase inhibitor that has been approved for the treatment of patients with advanced NSCLC that is ALK-positive but resistant to crizotinib. Next-generation ALK tyrosine kinase inhibitors were compared to brigatinib. Patients with ALK+ NSCLC who had disease progression on alectinib or ceritinib were enrolled in the phase 2 brigAtinib-2 (NCT03535740) trial, receiving 180 mg of brigatinib once daily (after 7-d 90-mg lead-in). The overall response rate, as determined by an independent review committee (IRC) served as the primary outcome measure (ORR). Research into circulating tumor DNA (ctDNA) was conducted.
Confirmed IRC-ORR was 26.2% (95% CI: 18.0-35.8) among 103 patients (data cutoff: September 30, 2020; median follow-up: 10.8 [0.5-17.7] mo), the median duration of response was 6.3 months (95% CI: 5.6-not attained), and median progression-free survival (mPFS) was 3.8 months (95% CI: 3.5-5.8). Patients with a ctDNA detectable baseline ALK fusion (n=64) had a median progression-free survival (mPFS) of 1.9 months (95% CI: 1.8-3.7). The overall response rate (IRC-ORR) for 86 patients who developed disease while on alectinib was 29.1% (95% CI: 19.8-39.9), and the median progression-free survival (mPFS) was 3.8 months (95% CI: 1.9-5.4). Three-thirds of baseline ctDNA samples (26 of 78) included resistance mutations, with G1202R mutations accounting for 54% (14 of 26) of all mutations and EML4-ALK variant 3 being present in 52% (33 of 64) of patients with detectable ALK fusion.
Increased creatine phosphokinase (32%), and diarrhea (27%), were the most common side effects across all grades associated with therapy. The average brigatinib dose intensity was 85.9% (180 mg once daily). For patients with ALK+ NSCLC after treatment with either cetuximab or alectinib, brigatinib was found to have only little effect in the brigAtinib-2 trial. In patients lacking detectable baseline plasma ALK fusion, brigatinib resulted in a prolonged mPFS.