Brigatinib Outperforms Crizotinib in Advanced ALK-Positive NSCLC: Presented at ELCC

By Jenny Powers

GENEVA -- April 16, 2019 -- In a head-to-head comparison of brigatinib versus the current standard of crizotinib, brigatinib showed superior progression-free survival (PFS) and intracranial activity in patients with anaplastic lymphoma kinase (ALK)-positive non-small-cell lung cancer (NSCLC).

The findings were presented here at the 2019 European Lung Cancer Conference (ELCC) by Raffaele Falifano, MD, NHS Christie Foundation Trust, Manchester, United Kingdom, and colleagues.

Investigator-assessed median PFS was not reached with brigatinib versus 9.8 months with crizotinib.

One-year PFS rates were 67% with brigatinib versus 43% with crizotinib.

The systemic objective response rates (ORR) were 71% brigatinib versus 60% with crizotinib. The ORR with brigatinib comprised 4 confirmed complete responses and 67 partial responses. With crizotinib there were 5 complete responses and 55 partial responses.

“Brigatinib is a next generation ALK/ROS1 inhibitor with broad activity that has demonstrated high response rates and the longest reported median PFS of any ALK inhibitor across 2 independent trials,” said DR. Falifano.

The open-label, multicentre ALTA-1L trial enrolled 275 patients with advanced ALK-positive NSCLC who had received 1 or no prior systemic therapy for advanced NSCLC, including patients with symptomatic central nervous system metastases. Patients were randomised to brigatinib 180 mg once daily preceded by a 7-day lead-in (n = 137) at 90 mg or to crizotinib 250 mg twice daily (n = 138).

Regarding intracranial efficacy, 18 patients with baseline brain metastasis were assigned to brigatinib and 21 patients to crizotinib. These cohorts demonstrated ORRs of 76% and 21%, respectively. With brigatinib 11% of patients had a complete response and 29% had a partial response, whereas with crizotinib, the entire ORR consisted of 29% partial responses.

The most commonly reported grade ≥3 treatment-emergent adverse events (TEAEs) in the brigatinib group were increased blood creatinine phosphokinase (16.2%), increased lipase (13.2%), and hypertension (9.6%). The most common grade ≥3 TEAEs in the crizotinib group were increased alanine aminotransferase (9.5%), aspartate aminotransferase (5.8%), and lipase (5.1%).

Any grade interstitial lung disease/pneumonitis occurred in 3.7% of patients in the brigatinib arm and in 2.2% of patients in the crizotinib arm.

Funding for this study was provided by ARIAD Pharmaceuticals.

[Presentation title: Brigatinib (BRG) vs Crizotinib (CRZ) in the Phase III ALTA-1L Trial. Abstract 106O]

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