Brigatinib Superior to Crizotinib in ALK NSCLC

According to the final results of the ALTA-1L trial, presented at the 2021 Virtual ESMO Congress, brigatinib demonstrated greater survival benefit over crizotinib in patients with ALK+ non-small cell lung cancer (NSCLC).

The final results came following 2 planned interim analyses which showed brigatinib BIRC-assessed progression-free survival (PFS) was superior to crizotinib.

Patients with ALK TKI-naive advanced ALK+ NSCLC were enrolled and stratified by baseline brain metastases and prior chemotherapy, those with one prior chemotherapy treatment for advanced NSCLC, and asymptomatic brain metastases were allowed. Patients were randomized (1:1) to receive either brigatinib 180mg once daily (7-day lead-in at 90mg) or crizotinib 250 mg twice a day. Those in the crizotinib arm were offered brigatinib at progression.

The primary end point was BIRC-assessed PFS (RECIST v1.1), while the secondary end points included confirmed intracranial objective response rate (iORR), iPFS by BIRC, overall survival (OS), safety, and quality of life.

137 patients were randomized to the brigatinib group, 26% had prior chemotherapy and 29% had baseline brain metastases. Among the 138 in the crizotinib group, those with prior chemotherapy and baseline brain metastases were 27% and 30%, respectively. 

As of January 2021, the median follow-up for patients in the brigatinib and crizotinib groups were 40.4 months and 15.2 months, respectively. Furthermore, the median PFS was 24.0 months (95% CI: 18.4–43.2) for brigatinib, compared to 11.1 months (95% CI: 9.1–13.0) for crizotinib; the respective 3-year PFS rate was 43% and 19%.

Additionally, the median duration of response was 33 months for brigatinib and 14 months for crizotinib. The median OS was not reached in either group, but the 3-year OS was 71% in the brigatinib arm and 68% in the crizotinib arm.

The most common grade ≥3 adverse events (AEs) included creased CPK (26%) and lipase (15%), hypertension (14%); CRZ: increased ALT (10%), lipase, (8%), AST (7%). 13.2% of patients in the brigatinib arm and 8.8% in the crizotinib arm discontinued due to AEs.

“[Brigatinib] demonstrated durable overall and intracranial efficacy, and the tolerability profile remained consistent and manageable despite extended treatment duration, confirming [brigatinib] as an effective standard-of-care treatment in pts with treatment-naive ALK+ NSCLC,” concluded Sanjay Popat, Medicine, Royal Marsden Hospital NHS Foundation Trust, London et al.—Alexandra Graziano

S. Popat, H.R. Kim, M. Ahn. Brigatinib (BRG) vs crizotinib (CRZ) in ALK TKI–naive ALK+ NSCLC: Final results from ALTA-1L. Presented at: the ESMO Virtual Congress 2021; September 16-21, 2020; virtual. Abstract 1195P.