Yi‑Long Wu, MD

As reported in The New England Journal of Medicine by Yi‑Long Wu, MD, of Guangdong Lung Cancer Institute, Guangdong Provincial People’s Hospital, 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 non–small cell lung cancer (NSCLC).¹

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 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 follow:

• 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, the sites of recurrence in the alectinib group vs the chemotherapy group were local/regional recurrence alone in 6.9% vs 17.3%, distant recurrence alone in 2.3% vs 17.3%, and local/regional and distant recurrence in 1.5% vs 3.9%; a new primary lung cancer was identified in one vs zero patients.

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; at the time of analysis, death had occurred in two patients in the alectinib group and four patients in the chemotherapy group.

Adverse Events

The safety population included 128 patients in the alectinib group and 120 patients in the chemotherapy group. The most common adverse events of any grade were increased creatinine 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 the alectinib group, most commonly increased creatinine kinase (6.2%) vs 30.8% of the chemotherapy group, most commonly decreased neutrophils (10%); treatment-related grade 3 or 4 adverse events occurred in 18.0% vs 27.5%. Serious adverse events occurred in 13.3% vs 8.3% of patients; the most common serious adverse evense were appendicitis (3.1%), pneumonia (2.3%), and myocardial infarction (1.6%) in the alectinib group and nausea (1.7%) and decreased neutrophils (1.7%) in the chemotherapy group. Adverse events led to discontinuation of treatment in 5.5% vs 12.5% of patients. No fatal adverse events were reported.

Benjamin J. Solomon, MB, BS, PhD

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 and Benjamin J. Solomon, MB, BS, PhD, of the -Department of Medical Oncology, Peter MacCallum Cancer Centre, Melbourne, are the corresponding authors of the The New England Journal of Medicine article. 

DISCLOSURE: The study was funded by F. Hoffmann–La Roche. Dr. Wu has served as a speaker or consultant for AstraZeneca, BeiGene, Boehringer Ingelheim, Hengrui Company China, F. Hoffmann–La Roche, and Pfizer; serves on the board for the Chinese Thoracic Oncology Group; and is a co–principal investigator on trials supported by Eli Lilly, F. Hoffmann–La Roche, and Sanofi. For full disclosures of the study authors, visit nejm.org.

REFERENCE

1. Wu YL, Dziadziuszko R, Ahn JS, et al: Alectinib in resected ALK-positive non–small-cell lung cancer. N Engl J Med 390:1265-1276, 2024.