Adjuvant ALK inhibition after complete resection of ALK-Positive NSCLC: interpreting ALINA and ELEVATE within the evolving perioperative landscape

Complete resection can be curative for anaplastic lymphoma kinase (ALK)-positive non-small cell lung cancer (NSCLC), but occult systemic or central nervous system (CNS) disease may cause relapse. ALINA and ELEVATE provide positive randomized adjuvant evidence that must be interpreted alongside negative findings, emerging neoadjuvant strategies, and practical barriers to care. This narrative review centers on adjuvant ALK inhibition after complete resection within the evolving perioperative landscape. In ALINA, alectinib or platinum chemotherapy was assigned before any postoperative systemic therapy; ELEVATE assigned ensartinib or placebo after surgery and any selected chemotherapy. Both improved disease-free survival and CNS outcomes within their randomized comparisons; neither ranked the agents nor isolated chemotherapy’s incremental contribution. The negative E4512 crizotinib trial reinforces the need for agent- and setting-specific evidence. Early neoadjuvant studies report pathologic regression and surgical feasibility, but do not establish whether adding a preoperative phase improves long-term outcomes. ADAURA provides lessons in survival and off-treatment follow-up in epidermal growth factor receptor (EGFR)-mutated NSCLC without determining ALK-specific timing or duration. Access encompasses molecular diagnosis before systemic treatment, coordination of investigational preoperative care, and sustained postoperative treatment and monitoring. Residual-disease biology, molecular residual disease (MRD), and paired tissue-plasma analysis at relapse inform the translational discussion; MRD-guided treatment adaptation remains investigational. Current adjuvant decisions should follow the relevant randomized evidence, pathologic anatomy, prior treatment, and patient-specific feasibility. Perioperative research should test the incremental value of preoperative treatment, chemotherapy sequencing, duration, and MRD-guided strategies using appropriate surgical and long-term endpoints. Timely molecular testing and access to treatment are essential to implementation.