Adjuvant alectinib was associated with early improvements in health-related quality of life that were maintained over 2 years of treatment in patients with resected ALK-positive non–small cell lung cancer (NSCLC). The new analysis of the phase III ALINA trial, reported by Dziadziuszko et al in The Lancet Oncology, also found a manageable safety profile with alectinib despite its substantially longer treatment duration compared with chemotherapy.
The primary ALINA analysis previously showed that adjuvant alectinib significantly improved disease-free survival compared with platinum-based chemotherapy. The current report focuses on safety and quality of life, which are particularly important in the adjuvant setting because patients have undergone complete tumor resection and may remain on treatment while disease free. Patients with ALK-positive NSCLC also tend to be younger than those with ALK-negative disease, making the effects of treatment on daily life particularly relevant.
Study Details
ALINA is a global, open-label, randomized phase III trial that enrolled 257 patients with completely resected, ALK-positive stage IB (tumors ≥ 4 cm), II, or IIIA NSCLC and an ECOG performance status of 0 or 1. Patients were randomly assigned to oral alectinib at 600 mg twice daily for 24 months or four 21-day cycles of intravenous platinum-based chemotherapy.
Health-related quality of life was assessed using the 36-item Short Form Health Survey version 2 (SF-36v2), which measures physical and mental health across eight domains. Quality-of-life outcomes were exploratory. Because chemotherapy ended at week 12, direct comparisons between the treatment groups were limited to the first 12 weeks.
Key Findings
At week 12, alectinib was associated with clinically meaningful improvement from baseline in mental health–related quality of life and in several individual domains, including bodily pain, physical limitations affecting usual activities, mental health, social functioning, and vitality. No health domains improved with chemotherapy, and general health and vitality declined by clinically meaningful amounts. Physical component scores remained stable in both groups.
Quality of life continued to improve during the 2 years of alectinib treatment. At week 96, mean mental and physical component scores with alectinib were 49.9 and 48.8, respectively, approaching the general population norm of 50. In the chemotherapy group, quality of life began to improve after treatment ended at week 12, and by week 96 mental and physical scores had also returned to levels similar to population norms. The investigators cautioned that the groups could not be directly compared after week 12 because patients receiving chemotherapy were no longer on active treatment.
Treatment-related adverse events of any grade occurred in 93% of patients receiving alectinib and 89% receiving chemotherapy, but severe events were less frequent with alectinib. Grade 3 or 4 treatment-related adverse events occurred in 18% and 28% of patients, respectively, and serious treatment-related adverse events occurred in 2% and 7%. Treatment-related adverse events led to discontinuation in 5% of patients receiving alectinib and 12% receiving chemotherapy. No deaths due to adverse events occurred in either group.
The most common grade 3 or 4 adverse events with alectinib were increased blood creatine phosphokinase (6%), increased alanine aminotransferase (2%), and increased blood bilirubin (2%). With chemotherapy, the most common were decreased neutrophil count (10%), neutropenia (8%), and nausea (4%). Adverse events with alectinib that lasted more than 4 months were predominantly grade 1 or 2 and did not lead to treatment discontinuation.
The authors noted that interpretation of the quality-of-life findings is limited by the open-label design and underrepresentation of Black patients.
Together with the previously reported disease-free survival benefit, the investigators said the safety and quality-of-life findings support adjuvant alectinib as “an important new standard-of-care” for patients with resected ALK-positive NSCLC.
Rafal Dziadziuszko, MD, PhD, of the Medical University of Gdansk in Poland, is the corresponding author of the article.
DISCLOSURE: The study was funded by F. Hoffmann-La Roche. Dr. Dziadziuszko reported relationships with Roche, Pfizer, AstraZeneca, Novartis, Merck Sharp & Dohme, Takeda, GlaxoSmithKline, Amgen, and others. Other authors reported relationships with industry. For full disclosures of the study authors, visit thelancet.com/oncology.
