Head-to-head comparison of two ALK inhibitors

Brigatinib showed a statistically and clinically relevant improvement in PFS vs crizotinib in patients with anaplastic lymphoma kinase (ALK) inhibitor-naïve, ALK-positive non-small cell lung cancer (NSCLC). This was the result of the first interim analysis from the ALTA-1L study comparing the ALK inhibitors brigatinib vs crizotinib in that patient population.

Brigatinib, a next-generation ALK inhibitor, has robust efficacy in patients with ALK-positive NSCLC that is refractory to crizotinib. Until this ELCC meeting, the efficacy of brigatinib as compared with crizotinib in patients with advanced ALK-positive NSCLC who have not previously received an ALK inhibitor was unclear.

Brigatinib or crizotinib

The open-label, multicentre phase 3 ALTA-1L study enrolled patients with advanced ALK-positive NSCLC. Eligible patients had ≤1 prior systemic therapy for advanced NSCLC. Asymptomatic central nervous system metastases were allowed. A total of 275 patients randomly received either brigatinib 180 mg once daily with 7-day lead-in at 90 mg or crizotinib 250 mg twice daily. The median age in these two groups was 58 and 60 years; 26% and 27% received prior chemotherapy for advanced disease, and 29% and 30% had baseline brain metastases, respectively.

Progression-free survival benefit

Raffaele Califano (University Hospital of South Manchester, United Kingdom) presented the data. The primary endpoint was progression-free survival (PFS), assessed by blinded independent review committee (BIRC; RECIST v1.1). After a median follow-up of 11.0 and 9.3 months in the brigatinib and crizotinib arms, respectively, and the occurrence of 99 PFS events, brigatinib met the prespecified threshold for statistical superiority vs crizotinib in the primary endpoint (hazard ratio 0.49; log-rank P=0.0007). The median PFS in the brigatinib arm was not reached vs 9.8 months in the crizotinib arm.

Adverse events

Most common grade ≥3 treatment-emergent adverse events were:

  • In the brigatinib arm: increased blood creatine phosphokinase (16.2%) and lipase (13.2%), hypertension (9.6%); and
  • In the crizotinib arm: increased alanine aminotransferase (9.5%), aspartate aminotransferase (5.8%), and lipase (5.1%). Any grade interstitial lung disease or pneumonitis occurred in 3.7% and 2.2% in the brigatinib and crizotinib arms, respectively. Discontinuations due to adverse events occurred in 11.8% and 8.8%, respectively.
  1. Califano R. Brigatinib (BRG) vs crizotinib (CRZ) in the phase III ALTA-1L trial. ELCC 2019, Geneva, Switzerland; abstract 106O.

The content and interpretation of these conference highlights are the views and comments of the speakers/authors.