WCLC 2017: Lorlatinib in ALK-Positive/ROS1-Positive Advanced Lung Cancer
In patients with ALK-positive and ROS1-positive non–small cell lung cancer (NSCLC), lorlatinib, a brain-penetrant ALK/ROS1 tyrosine kinase inhibitor, exhibited clinical activity against lung tumors and brain metastases, according to the results of a phase II clinical trial presented at the 2017 International Association for the Study of Lung Cancer (IASLC) World Conference on Lung Cancer (Abstract OA 05.06) in Yokohama, Japan. “We saw excellent intracranial responses in all patient groups, including those who were heavily pretreated,” commented lead investigator Benjamin Solomon, MBBS, PhD, FRACP, of Peter MacCallum Cancer Centre, Melbourne, Australia, in a recent press release.
A total of 275 patients with or without asymptomatic, untreated, or treated brain metastases took part in the study. The objective response rate (ORR) and intracranial ORR for the clinically relevant study cohorts follow:
- ALK-positive, treatment-naive: ORR, 90%; intracranial ORR, 75%
- ALK-positive, previously treated with crizotinib with or without chemotherapy: ORR, 69%; intracranial ORR, 68%
- ALK-positive, previously treated with an ALK inhibitor other than crizotinib with or without chemotherapy: ORR, 33%; intracranial ORR, 42%
- ALK-positive, previously treated with two or three prior ALK inhibitors with or without chemotherapy: ORR, 39%; intracranial ORR, 48%
- ROS1-positive regardless of prior treatment: ORR, 36%; intracranial ORR, 56%.
Lorlatinib was reported to be generally well tolerated, with a rate of treatment discontinuation due to drug-related adverse events of 3%. The most common adverse events reported with lorlatinib were hypercholesterolemia (81%), hypertriglyceridemia (60%), edema (43%), and peripheral neuropathy (30%).