Dr Simon on the ALK Inhibitor Selection Process in ALK+ NSCLC

George R. Simon, MD, FACP, FCCP, senior member, Chemical Biology and Molecular Medicine Program, Moffitt Cancer Center, delineates the process of selecting appropriate ALK inhibitors for the treatment of patients with ALK-positive non–small cell lung cancer(NSCLC).

Simon begins by highlighting alectinib (Alecensa), brigatinib (Alunbrig), and lorlatinib (Lorbrena), which are all approved by the FDA for the treatment of patients with metastatic ALK-positive NSCLC, as detected by an FDA-approved test. He also points to ensartinib (X-396), which is currently being reviewed by the FDA for the treatment of patients with metastatic ALK-positive NSCLC. Notably, on April 18, 2024, the regulatory agency expanded the indication for alectinib when it approved the agent for use as adjuvant treatment following tumor resection in patients with ALK-positive NSCLC whose tumors are at least 4 cm or node positive.

When selecting an ALK inhibitor in the metastatic setting, Simon notes that the decision-making process is multifaceted, including the consideration of patient-specific factors such as baseline health. Potential resistance mechanisms can be associated with each of the approved ALK inhibitors; however, alternative medications can sometimes counteract these mechanisms, Simon explains. The known safety profile of each agent is also discussed when selecting between these agents, Simon adds.

Furthermore, when choosing an ALK inhibitor for eligible patients with metastatic NSCLC, it is crucial to account for the specific genetic mutation or alteration detected in an individual patient, Simon continues. For example, in patients with ALK G1202R mutations, lorlatinib has been the only agent associated with efficacy in this subgroup, Simon explains. Determining the specific ALK alteration and consulting a treatment algorithm to match mutations with corresponding sensitive drugs can help facilitate personalized treatment plans for individual patients, Simon emphasizes.

Simon underscores the importance of individualized therapy selection in ALK inhibitor treatment. By integrating patient health status, known resistance mechanisms, drug toxicities, and mutation-specific sensitivities, oncologists can optimize treatment for patients with ALK-positive tumors, he concludes.