The third-generation ALK and ROS1 inhibitor lorlatinib yielded strong treatment activity in patients with ALK-positive non–small-cell lung cancer (NSCLC), according to a phase II study. Good response rates were seen in patients with varying treatment history, including those who were treatment-naive and those who had progressed on previous ALK-directed therapy.
ALK rearrangements occur in 3% to 5% of NSCLC cases, and are typically treated with crizotinib, alectinib, or ceritinib. “However, most patients treated with crizotinib relapse over time because of acquired resistance,” wrote study authors led by Benjamin J. Solomon, MBBS, of the Peter MacCallum Cancer Centre in Melbourne. Though the other ALK-targeted therapies were developed to overcome that resistance, “most patients will develop resistance to second-generation tyrosine kinase inhibitors or develop disease progression in the CNS.”
Lorlatinib is a novel third-generation inhibitor of ALK and ROS1, and it showed promising results in a phase I trial. In this phase II trial, researchers included six expansion cohorts based on ALK mutation status and prior treatment. The results were published in Lancet Oncology.
Source: Cancer Network