Alectinib Significantly Improves DFS Vs Chemo in Resected ALK+ NSCLC
Investigators of the phase 3 ALINA trial report no unexpected safety findings with alectinib in ALK-positive non–small cell lung cancer.
"Adjuvant alectinib represents an important efficacious new treatment strategy for patients with resected ALK-positive NSCLC of stage IB, II, or IIIA," according to the study authors.
Adjuvant treatment with alectinib (Alecensa) conferred a significant disease-free survival (DFS) improvement compared with platinum-containing chemotherapy in patients with resected ALK-positive non–small cell lung cancer (NSCLC), according to findings from the phase 3 ALINA trial (NCT03456076) published in New England Journal of Medicine.1
At 2 years, DFS among those with stage II or IIIA disease was reported in 93.8% of the alectinib arm and 63.0% of the chemotherapy arm. The 3-year DFS rates in each respective arm were 88.3% vs 53.3%. Alectinib reduced the risk of disease recurrence or death by 76% (HR, 0.24; 95% CI, 0.13-0.45; P <.001).
Across the intent-to-treat population, the 2-year DFS rates in the alectinib and chemotherapy arms were 93.6% vs 63.7%, respectively, and the 3-year rates were 88.7% vs 54.0% (HR, 0.24; 95% CI, 0.13-0.43; P <.001). The DFS benefit with alectinib generally extended across patient subgroups based on disease stage, race, sex, and smoking status. Additionally, treatment with alectinib reduced the risk of central nervous system (CNS) disease recurrence or death compared with chemotherapy (HR, 0.22; 95% CI, 0.08-0.58).
Overall survival (OS) data were immature at the time of the analysis, with an event-patient ratio of 2.3%. Overall, 2 patients receiving alectinib and 4 of those receiving chemotherapy had died.
“Adjuvant alectinib showed a significant benefit with respect to disease-free survival as compared with chemotherapy, as well as a mainly low-grade safety profile with few discontinuations due to [AEs],” Yi-Long Wu, MD, from Guang‑dong Lung Cancer Institute, Guangdong Provincial People’s Hospital (Guangdong Academy of Medical Sciences), Southern Medical University, and coauthors wrote.1 “Adjuvant alectinib represents an important efficacious new treatment strategy for patients with resected ALK-positive NSCLC of stage IB, II, or IIIA.”
In the open-label, international ALINA trial, 257 patients were randomly assigned 1:1 to receive alectinib orally at 600 mg twice daily for 24 months (n = 130) or platinum-based chemotherapy intravenously across 21-day cycles (n = 127). Treatment options in the chemotherapy arm included cisplatin at 75 mg/m2 plus vinorelbine at 25 mg/m2, gemcitabine at 1250 mg/m2, or pemetrexed at 500 mg/m2.
The trial’s primary end point was DFS. Secondary end points included OS and safety. CNS DFS, defined as the time from random assignment to disease recurrence in the CNS or death from any cause, was an exploratory end point.
Patients 18 years and older with completely resected histologically confirmed stage IB, II, or IIIA NSCLC and documented ALK-positive disease were eligible for enrollment on the trial. Additional eligibility requirements included having an ECOG performance status of 0 or 1 and no prior systemic anticancer therapy.
The median age was 54 years in the alectinib arm and 57 years in the chemotherapy arm. In each respective arm, most patients were Asian (55.4% vs 55.9%), had an ECOG performance status of 0 (55.4% vs 51.2%), never smoked (64.6% vs 55.1%), had stage IIIA disease (53.1% vs 55.1%), and nonsquamous histology (95.4% vs 97.6%). Additionally, the most common surgical procedure for lung cancer in each arm was lobectomy (96.9% vs 92.1%).
Overall, 98.4% of patients who received alectinib and 93.3% of those who were treated with chemotherapy had at least 1 AE. Common AEs in the alectinib group included creatine kinase level increases (43.0%) and constipation (42.2%), while frequent toxicities in the chemotherapy arm included nausea (72.5%) and decreased appetite (29.2%). Treatment-related AEs (TRAEs) affected 93.8% and 89.2% of patients in each respective arm, and grade 3/4 TRAEs occurred in 18.0% and 27.5%.
Investigators reported that 25.8% and 10.0% of patients in the alectinib and chemotherapy arms, respectively, had AEs leading to dose reductions. Dose interruptions due to AEs occurred in 27.3% and 18.3% of patients in each respective arm, and AEs resulting in treatment discontinuation affected 5.5% and 12.5%.
Of note, the FDA approved adjuvant alectinib for patients with ALK-positive NSCLC in April 2024.2 Supporting findings for the approval came from the ALINA trial.
References
- Wu YL, Dziadziuszko R, Ahn JS, et al. Alectinib in resected ALK-positive non-small-cell lung cancer. N Engl J Med. 2024;390(14):1265-1276. doi:10.1056/NEJMoa2310532
- FDA approves Genentech's Alecensa as first adjuvant treatment for people with ALK-positive early-stage lung cancer. News release. Genentech. April 18, 2024. Accessed April 19, 2024. https://shorturl.at/zSV29
These data support less restrictive clinical trial eligibility criteria for those with metastatic NSCLC. This is especially true regarding both targeted therapy and immunotherapy treatment regimens.
