On 18 April 2024, the US Food and Drug Administration (FDA) approved alectinib (Alecensa, Genentech, Inc.) for adjuvant treatment following tumour resection in patients with anaplastic lymphoma kinase (ALK)-positive non-small cell lung cancer (NSCLC), as detected by an FDA-approved test.
Efficacy was demonstrated in a global, randomised, open-label study (ALINA, NCT03456076) in patients with ALK-positive NSCLC who had complete tumour resection. Eligible patients were required to have resectable Stage IB (tumours ≥ 4 cm) to IIIA NSCLC (by AJCC 7th edition) with ALK rearrangements identified by a locally performed FDA-approved ALK test or by a centrally performed VENTANA ALK (D5F3) CDx assay. A total of 257 patients were randomised (1:1) to receive alectinib 600 mg orally twice daily or platinum-based chemotherapy following tumour resection.
The major efficacy outcome measures were disease-free survival (DFS) in the subgroup of patients with stage II-IIIA NSCLC and DFS in the overall study population (stage IB-IIIA), as assessed by investigator. In patients with stage II-IIIA NSCLC, median DFS was not reached (95% confidence interval [CI] not estimable [NE], NE) in the alectinib arm and 44.4 months (95% CI 27.8, NE) in the chemotherapy arm (hazard ratio [HR] 0.24, 95% CI 0.13, 0.45; p < 0.0001). Similar results were seen in the overall study population with median DFS not reached (95% CI NE, NE) in the alectinib arm and 41.3 months (95% CI 28.5, NE) in the chemotherapy arm (HR 0.24, 95% CI 0.13, 0.43; p < 0.0001).
The most common (≥ 20%) adverse reactions in patients taking alectinib were hepatotoxicity, constipation, myalgia, COVID-19, fatigue, rash, and cough.
The recommended alectinib dose is 600 mg orally twice daily with food for 2 years or until disease recurrence or unacceptable toxicity.
This review was conducted under Project Orbis, an initiative of the FDA’s Oncology Center of Excellence (OCE). Project Orbis provides a framework for concurrent submission and review of oncology drugs among international partners. For this review, FDA collaborated with the Australian Therapeutic Goods Administration, Health Canada, Israel’s Ministry of Health, Switzerland’s Swissmedic, and United Kingdom’s Medicines and Healthcare products Regulatory Agency. The application reviews are ongoing at other regulatory agencies involved with Project Orbis.
This review used the Real-Time Oncology Review pilot programme, which streamlined data submission prior to the filing of the entire clinical application, and the Assessment Aid, a voluntary submission from the applicant to facilitate the FDA’s assessment. The FDA approved this application one month ahead of the FDA goal date.
This application was granted priority review and orphan drug designation.
Healthcare professionals should report all serious adverse events suspected to be associated with the use of any medicine and device to FDA’s MedWatch Reporting System.
For assistance with single-patient INDs for investigational oncology products, healthcare professionals may contact OCE’s Project Facilitate.