Use of Lorlatinib in ALK-Positive NSCLC
Posted: Monday, February 4, 2019
The findings of an ongoing phase II study were presented by Benjamin J. Solomon, MBBS, of the Peter MacCallum Cancer Centre, and colleagues in The Lancet Oncology. They analyzed the use of the third-generation inhibitor of ALK and ROS1 lorlatinib in ALK-positive non–small cell lung cancer, with or without central nervous system (CNS) metastases. “Consistent with its broad ALK mutational coverage and CNS penetration, lorlatinib showed substantial overall and intracranial activity” in ALK-positive patients, concluded the investigators.
Over 1 year, 276 patients were enrolled. A total of 30 patients were treatment-naive and had ALK-positive disease; 59 patients had ALK-positive disease and received crizotinib with (n = 32) or without (n = 27) previous chemotherapy; 28 patients had ALK-positive disease and had received 1 prior ALK tyrosine kinase inhibitor (not crizotinib) with or without chemotherapy; 112 had ALK-positive disease with 2 (n = 66) or 3 (n = 46) previous ALK tyrosine kinase inhibitors with or without chemotherapy; and 47 had ROS1-positive disease with any previous treatment.
The objective response rate was 90% in the treatment-naive patients. In those with ALK-positive disease who had 1 previous ALK tyrosine kinase inhibitor, the objective response rate was 47%. The objective response rate was 69.5% in those who had received previous treatment with crizotinib alone, 32.1% in those who had received 1 previous ALK tyrosine kinase inhibitor (not crizotinib), and 38.7% in those who had received two or more previous ALK tyrosine kinase inhibitors. In addition, the intracranial overall response rate in 89 patients with measurable CNS lesions was 60%, with a complete response noted in 21%.
The most common treatment-related adverse events in all patients were hypercholesterolemia (81%) and hypertriglyceridemia (60%).
Disclosure: The study authors’ disclosure information may be found at thelancet.com.