Lorlatinib shows therapeutic potential in advanced ROS1-positive NSCLC

The third-generation tyrosine kinase inhibitor (TKI) lorlatinib appears to be safe and have potent therapeutic effect in advanced nonsmall-cell lung cancer (NSCLC) harbouring ROS1 mutation, including patients with central nervous system metastases and those with previous crizotinib exposure, according to the results of a phase I/II trial.

The trial involved 69 patients with ROS1-positive NSCLC, among whom 21 (30 percent) were TKI-naïve, 40 (58 percent) had previously received crizotinib as their only TKI, and eight (12 percent) had previously received one noncrizotinib ROS1 TKI or ≥2 ROS1 TKIs. Lorlatinib was administered orally at 100 mg once daily in continuous 21-day cycles until disease progression, unacceptable toxicity, withdrawal of consent or death.

Objective response occurred in 13 (62 percent) TKI-naïve patients and 14 (35 percent) patients previously treated with crizotinib as their only TKI. Intracranial responses were recorded in seven of 11 (64 percent) TKI-naïve patients and 12 of 24 (50 percent) previous crizotinib-only patients. The median follow-up duration for response was 21.1 months.

In terms of safety, commonly reported grade 3–4 treatment-related adverse events (AEs) were hypertriglyceridaemia (19 percent) and hypercholesterolaemia (14 percent). Serious treatment-related AEs occurred in 7 percent of patients. There were no records of treatment-related deaths.

The present data suggest the potential of lorlatinib as an important next-line targeted agent, given that crizotinib-refractory patients have few treatment options, the researchers said.