Brigatinib Safe, Effective for Crizotinib-Refractory ALK+ NSCLC
According to study data being presented by Scott N. Gettinger, MD, Yale School of Medicine, New Haven, Connecticut, et al at the virtual 2021 American Society of Clinical Oncology (ASCO) Annual Meeting, brigatinib demonstrated improved progression-free survival (PFS) along with manageable safety in patients with crizotinib-refractory ALK-positive non-small-cell lung cancer (NSCLC).
In the single-arm, open-label ALTA trial of brigatinib in patients with advanced malignancies, 222 patients with crizotinib-refractory ALK-positive NSCLC were randomized to receive brigatinib 90 mg once daily (arm A; n = 112) or 180 mg once daily with a 7-day lead-in at 90 mg (arm B; n = 110).
The primary end point was confirmed objective response rate (cORR) per investigator, while secondary endpoints included cORR per independent review committee (IRC), duration of response (DoR), PFS, and overall survival (OS).
The ALTA study ended in February 2020 with a median follow-up of 19.6 in arm A and 28.3 in arm B. At this point, a total of 10 and 17 patients were still receiving treatment in arms A and B, respectively.
Among patients with measurable baseline brain metastases (26 in arm A and 18 in arm B) the IRC-assessed intracranial cORR was 50% in arm A and 67% in arm B.
The median PFS was 9.2 months (95% CI, 7.4-11.1) in arm A and 15.6 months (95% CI; 11.1-18.5) in arm B. The Kaplan-Meier (KM) estimated median intracranial DoR was 9.4 months and 16.6 months in arms A and B, respectively (95% CI, 3.7 to not reached in both arms).
Furthermore, the KM estimated 5-year OS was 31% in arm A and 43% in arm B, and no new safety signals were identified.
“Brigatinib showed sustained long-term activity, PFS, and manageable safety in patients with crizotinib-refractory ALK-positive NSCLC. The [dose received by arm B] led to numerically higher median PFS and OS. Final results are similar to those reported for other approved ALK tyrosine kinase inhibitors in this setting,” concluded Dr Gettinger et al.—Alexandra Graziano
Gettinger SN, Huber RM, Kim DW. Brigatinib (BRG) in ALK+ crizotinib (CRZ)-refractory non-small cell lung cancer (NSCLC): Final results of the phase 1/2 and phase 2 (ALTA) trials. Presented at: the 2021 ASCO Annual Meeting; June 4-8, 2021; virtual. Abstract 9071.
