Thomas E. Stinchcombe, MD, professor of medicine, Duke Cancer Institute, discusses remaining challenges in ALK-positive non­—small cell lung cancer (NSCLC).

Though patients are responding well to upfront next-generation TKIs, the optimal treatment strategy for patients who experience disease progression is unclear, says Stinchcombe.

Chemotherapy or single-agent lorlatinib (Lorbrena) are potential regimens with response rates around 40% to 45% and a progression-free survival benefit of 6 to 8 months, explains Stinchcombe. Importantly, lorlatinib has a high rate of central nervous system activity that may benefit patients with brain metastases.

Remaining questions regarding repeat tumor biopsy, the utility of circulating tumor DNA, and how to further personalize treatment for patients need to be explored further, highlights Stinchcombe.

Additionally, up to 50% of patients will not have an ALK mutation either because insensitive testing did not catch a mutation, or because the patient has ALK-independent mechanisms of resistance. Understanding the optimal treatment for these patients is critical going forward, Stinchcombe concludes.