LBA2 ALINA: Efficacy and safety of adjuvant alectinib versus chemotherapy in patients with early-stage ALK+ non-small cell lung cancer (NSCLC)

For patients (pts) with resected, stage IB–IIIA, ALK+ NSCLC, the recommended treatment after surgery is platinum-based chemotherapy (CT), which is associated with modest improvements in survival. In advanced ALK+ NSCLC, alectinib is a preferred first-line treatment. Here, we report data from the prespecified interim analysis of ALINA (NCT03456076), a global, phase III, open-label, randomised trial assessing the efficacy and safety of adjuvant alectinib compared with CT in pts with completely resected ALK+ NSCLC. Eligible pts were ≥18 years old, had an ECOG PS of 0/1 and completely resected, stage IB (≥4 cm)–IIIA, ALK+ NSCLC (per UICC/AJCC 7th edition). Pts were randomised 1:1 to receive either oral alectinib 600 mg twice daily, or up to four 21-day cycles of IV platinum-based CT. Randomisation was stratified by stage (IB vs II vs IIIA) and race (Asian vs non-Asian). Alectinib was given for up to 24 months or until disease recurrence, unacceptable toxicity, or withdrawal of consent. Primary endpoint: investigator-assessed disease-free survival (DFS), tested hierarchically first in the stage II–IIIA and then in the ITT population (stage IB–IIIA). Other endpoints included: CNS-DFS, overall survival (OS), safety. A total of 257 pts were randomised to receive alectinib (n=130) or CT (n=127); baseline characteristics were overall well balanced between arms. At data cutoff (26 June 2023), median follow up was 27.8 months. A significant DFS benefit was observed with alectinib vs CT in both the stage II–IIIA (HR 0.24; 95% CI: 0.13–0.45) and ITT populations (HR 0.24; 95% CI: 0.13–0.43; Table). A clinically meaningful CNS-DFS benefit was observed in the ITT population (HR 0.22; 95% CI 0.08–0.58). OS data were immature. No unexpected safety findings were observed. Alectinib is the first ALK inhibitor to significantly improve DFS compared with CT and provides an effective new treatment strategy for pts with resected ALK+ NSCLC.Table: LBA2Stage II–IIIAITT (Stage IB–IIIA)EfficacyAlectinib (n=116)CT (n=115)Alectinib (n=130)CT (n=127)DFS events, n (%)14 (12.1)45 (39.1)15 (11.5)50 (39.4)Median DFS, months (95% CI)NE44.4 (27.8–NE)NE41.3 (28.5–NE)Stratified HR (95% CI)0.24 (0.13–0.45)0.24 (0.13–0.43)p value<0.0001<0.000124-month DFS rate, %93.863.093.663.736-month DFS rate, %88.353.388.754.0Safety populationSafetyAlectinib(n=128)CT (n=120)Grade 3–4 AEs, n (%)*38 (29.7)37 (30.8)Serious AEs, n (%)17 (13.3)10 (8.3)Serious treatment-related AEs, n (%)2 (1.6)8 (6.7)AEs leading to treatment withdrawal, n (%)7 (5.5)15 (12.5)AEs, adverse events; NE, not estimable. ∗No Grade 5 AEs in either treatment arm Open table in a new tab