As reported in The New England Journal of Medicine by Yi-Long Wu, MD, and colleagues, the phase III ALINA trial has shown significantly improved disease-free survival with adjuvant alectinib vs platinum-based chemotherapy in patients with resected ALK-positive NSCLC.

Yi-Long Wu, MD

Study Details

In the open-label trial, 257 patients with completely resected stage IB (tumors ≥ 4 cm), II, or IIIA disease from sites in 26 countries were randomly assigned between August 2018 and December 2021 to receive oral alectinib at 600 mg twice daily for 24 months (n = 130) or platinum-based chemotherapy for four 21-day cycles (n = 127). Chemotherapy options were cisplatin at 75 mg/m² on day 1 of each cycle plus vinorelbine at 25 mg/m² on days 1 and 8; gemcitabine at 1,250 mg/m² on days 1 and 8; or pemetrexed at 500 mg/m² on day 1. Approximately 55% of patients were Asian and approximately 42% were White in each group; 65% vs 55% of patients were never-smokers. The primary endpoint of the trial was disease-free survival, tested hierarchically among patients with stage II or IIIA disease and then in the intention-to-treat (ITT) population (ie, including patients with stage IB disease).

Disease-Free Survival

In the alectinib group, 116 patients had stage II (n = 47; 36%) or IIIA disease (n = 69; 53%). In the chemotherapy group, 115 patients had stage II (n = 45; 34%) or stage IIIA disease (n = 70; 55%). Stage IB disease was present in 14 patients (10.8%) and 12 patients (9.4%), respectively.

Among patients with stage II or IIIA disease, disease-free survival was 93.8% in the alectinib group vs 63.0% in the chemotherapy group at 2 years and 88.3% vs 53.3% at 3 years. Median disease-free survival was not reached in the alectinib group vs 44.4 months (95% confidence interval [CI] =27.8 months to not evaluable) in the chemotherapy group (hazard ratio [HR] = 0.24, 95% CI = 0.13–0.45, P < .001).

Among patients in the ITT population, disease-free survival was 93.6% vs 63.7% at 2 years and 88.7% vs 54.0% at 3 years. Median disease-free survival was not reached in the alectinib group vs 41.3 months (95% CI = 28.5 months to not evaluable) in the chemotherapy group (HR = 0.24, 95% CI = 0.13–0.43, P < .001).

In subgroup analyses in the ITT population, hazard ratios for disease-free survival for the alectinib group vs the chemotherapy group included:

• 0.36 (95% CI = 0.17–0.79) among Asian patients and 0.16 (95% CI = 0.06–0.38) among non-Asian patients
• 0.27 (95% CI = 0.13–0.55) among never-smokers and 0.22 (95% CI = 0.08–0.57) among 95 former smokers
• 0.26 (95% CI = 0.11–0.60) among 123 men and 0.22 (95% = 0.10–0.50) among 134 women.  

Hazard ratios by disease stage were:

• 0.21 (95% CI = 0.02–1.84) for stage IB
• 0.24 (95% CI = 0.09–0.65) for stage II
• 0.25 (95% CI = 0.12–0.53) for stage IIIA.  

In the ITT population, central nervous system disease–free survival at 2 years was 98.4% (95% CI = 96.1%–100%) in the alectinib group vs 85.8% (95% CI = 78.8%–92.8%) in the chemotherapy group (HR = 0.22, 95% CI = 0.08–0.58). Data for overall survival were immature.

Adverse Events

The most common adverse events of any grade were increased creatine kinase (43.0%) and constipation (42.2%) in the alectinib group, and nausea (72.5%) and decreased appetite (29.2%) in the chemotherapy group. Grade 3 or 4 adverse events occurred in 29.7% of patients in the alectinib group (most commonly increased creatinine kinase in 6.2%) vs 30.8% of the chemotherapy group (most commonly decreased neutrophils in 10%). Serious adverse events occurred in 13.3% vs 8.3% of patients. Adverse events led to discontinuation of treatment in 5.5% vs 12.5% of patients. No fatal adverse events were reported.

The investigators concluded, “Among patients with resected ALK-positive NSCLC of stage IB, II, or IIIA, adjuvant alectinib significantly improved disease-free survival as compared with platinum-based chemotherapy.”

Dr. Wu, of Guangdong Lung Cancer Institute, Guangdong Provincial People’s Hospital Guangzhou, and Benjamin J. Solomon, MB, BS, PhD, of the Department of Medical Oncology, Peter MacCallum Cancer Centre, Melbourne, are the corresponding authors for The New England Journal of Medicine article.

Disclosure: The study was funded by F. Hoffmann–La Roche. For full disclosures of the study authors, visit nejm.org.