Alectinib in combination with bevacizumab as first-line treatment in ALK-rearranged non-small cell lung cancer (ALEK-B): a single-arm, phase 2 trial.

Up to 25% of patients with ALK-rearranged non-small cell lung cancer (NSCLC) experience disease progression within the first year of targeted therapy. This phase 2 trial investigates whether combining alectinib with bevacizumab can delay resistance mechanisms in advanced ALK-rearranged NSCLC. ALEK-B was an open-label, single-arm, single-center phase 2 trial (NCT03779191) evaluating alectinib (600 mg BID) and bevacizumab (15 mg/kg) in patients with advanced ALK-rearranged NSCLC confirmed by next-generation sequencing. The primary endpoint was the 12-month progression-free survival (PFS). Secondary endpoints included overall survival (OS), objective response rate (ORR), intracranial progression-free survival (icPFS), safety, and patient-reported quality of life (QoL). Between April 2020 and August 2022, 41 patients were enrolled, including 17.1% with brain metastases. As of December 14, 2023, with a median follow-up of 34.5 months, the 12-month PFS rate was 97.1% (95% CI 92.6-100). The 36-month PFS and OS rates were 64.2% (95% CI 56.1-85.2) and 87.9% (95% CI 74-96.6), respectively. The ORR was 100%, and the 36-month icPFS rate was 87.8% (95% CI 74.0-96.6). Grade 3-4 adverse events occurred in 46.3% of patients, most commonly proteinuria and hepatotoxicity, with no fatal events reported. QoL significantly improved from baseline at 12 months and was maintained through 36 months. These findings support the efficacy and safety of alectinib plus bevacizumab and justify further investigation in ALK-rearranged NSCLC.