Adjuvant Alectinib Approved in Europe for ALK+ Early-Stage NSCLC

The European Commission has approved single-agent alectinib (Alecensa) for use as adjuvant treatment after tumor resection in adult patients with ALK-positive non–small cell lung cancer (NSCLC) at high risk of recurrence.¹

The decision was supported by findings from the phase 3 ALINA trial (NCT03456076) in which alectinib (n = 116) improved disease-free survival (DFS) vs platinum-based chemotherapy (n = 115) in patients with stage II or IIIA disease (HR, 0.24; 95% CI, 0.13-0.45; P < .001).2 The 2-year DFS rates in the alectinib and chemotherapy groups were 93.8% and 63.0%, respectively; the respective 3-year DFS rates were 88.3% and 53.3%.

“When it comes to early stage ALK-positive NSCLC, surgery is not always enough as there remains a high risk of recurrence that leaves patients concerned about what’s to come,” Professor Fabrice Barlesi, MD, PhD, thoracic oncologist, Paris Saclay University and chief executive officer of Gustave Roussy Institute, stated in a news release.¹ “The magnitude of DFS benefit observed in the ALINA study was unprecedented and consistent across all disease stages. The use of early ALK testing will help to identify all patients that could benefit from this important new treatment option.”

The open-label, global, phase 3 ALINA study enrolled patients with completely resected, histologically confirmed stage IB, II, or IIIA NSCLC who had ALK-positive disease.2 Patients must have been at least 18 years of age and an ECOG performance status of 0 or 1. They needed to be candidates for platinum-based chemotherapy, and they could not have previously received systemic treatment.

Study participants were randomly assigned 1:1 to receive 600 mg of alectinib twice daily or platinum-based chemotherapy for four 21-day cycles. Chemotherapy included cisplatin at 75 mg/m2 on day 1 of each cycle plus vinorelbine at 25 mg/m2 on days 1 and 8; gemcitabine at 1250 mg/m2 on days 1 and 8; or pemetrexed at 500 mg/m2 on day 1. Stratification factors included disease stage (IB vs II vs IIIA) and race (Asian vs non-Asian). Treatment with alectinib continued until disease recurrence, intolerable toxicity, withdrawn consent, or for up to 24 months.

DFS served as the trial’s primary end point, and secondary end points comprised overall survival (OS) and safety. A key exploratory end points was central nervous system (CNS) DFS.

The baseline demographic and clinical characteristics of participants were generally well balanced between the treatment arms. The median patient age in the alectinib arm was 54 years vs 57 years in the chemotherapy arm. Across the arms, 52.1% of patients were female, 55.7% were Asian, 53.3% had an ECOG performance status of 0, and 59.9% were never smokers. Regarding disease stage at initial diagnosis, in the alectinib arm, 10.8% had stage IB disease, 36.2% had stage II disease, and 53.1% had stage III disease; these respective rates in the chemotherapy arm were 9.4%, 35.4%, and 55.1%. Most patients had nonsquamous histology (95.4% vs 97.6%) and had undergone lobectomy for their disease (96.9% vs 92.1%).

Additional data showed that in the intention-to-treat population, 2-year DFS rates with alectinib (n = 130) and chemotherapy (n = 127) were 93.6% and 63.7%, respectively; the 3-year DFS rates were 88.7% and 54.0%, respectively. The hazard ratio for DFS was 0.24 (95% CI, 0.13-0.43; P < .001).

Fifteen patients in the alectinib arm experienced disease recurrence vs 49 patients in the chemotherapy arm. The brain was the most common site of disease recurrence (alectinib, n = 4; chemotherapy, n = 14). The hazard ratio for CNS disease recurrence or death was 0.22 (95% CI, 0.08-0.58). Following recurrence, at least 1 subsequent treatment was administered to 13 and 43 patients in the alectinib and chemotherapy arms, respectively.

OS data were immature at the time of data cutoff, with a 2.3% event-patient ratio.

Regarding safety, at least one any-grade adverse effect (AE) occurred in 98.4% of those in the alectinib arm vs 93.3% of those in the chemotherapy arm; these effects were grade 3 or 4 for 29.7% and 30.8% of patients, respectively.

In the alectinib arm, the most common AEs were nausea (any grade, 7.8%; grade 3/4, 0%), increased creatine kinase (43.0% vs 6.2%), constipation (42.2% vs 0.8%), increased aspartate aminotransferase (41.4% vs 0.8%), increased alanine aminotransferase (33.6% vs 1.6%), increased blood bilirubin (33.6% vs 1.6%), decreased appetite (5.5% vs 0%), COVID-19 (28.9% vs 0%), myalgia (28.1% vs 0.8%), anemia (23.4% vs 0%), vomiting (7.0% vs 0%), increased alkaline phosphatase (25.0% vs 0%), decreased white cell count (1.6% vs 0%), decreased neutrophil count (2.3% vs 0%), asthenia (10.9% vs 0%), neutropenia (1.6% vs 0%), increased creatinine (14.8% vs 0.8%), cough (14.8% vs 0.8%), fatigue (14.1% vs 0.8%), rash (14.1% vs 0.8%), malaise (4.7% vs 0%), increased weight (13.3% vs 0.8%), diarrhea (12.5% vs 0.8%), headache (10.9% vs 0%), dyspnea (10.2% vs 0.8%), dysgeusia (10.2% vs 0%), and peripheral edema (10.2% vs 0%).

References

1. European Commission approves Roche’s Alecensa as the first and only targeted adjuvant treatment for people with ALK-positive early-stage lung cancer. News release. Roche. June 10, 2024. Accessed June 10, 2024. https://www.roche.com/media/releases/med-cor-2024-06-10
2. Wu Y-L, 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:10.10156/NEJMoa2310532