Is the price of lorlatinib generic drugs low in Laos?

Lorlatinib is a highly potent third-generation ALK and ROS1 tyrosine kinase inhibitor with good brain penetration and broad coverage of ALK mutations. In a phase 1 study, it showed significant activity in patients with ALK-positive non-small cell lung cancer, particularly in those with central nervous system (CNS) metastases and disease progression following ALK-directed therapy. This study aims to further investigate the systemic and intracranial anti-tumor effects of lorlatinib in patients with ALK-positive advanced non-small cell lung cancer.

In this Phase 2 study, we included patients with histologically or cytologically confirmed ALK-positive or ROS1-positive, advanced non-small cell lung cancer, with or without CNS metastases, with a performance status score of 0, 1, or 2 in the Eastern Cooperative Oncology Group, and adequate end-organ function. Patients were assigned to 6 different expansion cohorts (EXP1-6) based on their ALK and ROS1 status and 100 mg of lorlatinib taken continuously daily in a 21-day treatment cycle. The primary endpoints of the study were overall response and intracranial tumor response as assessed by independent central review, which were performed in pooled subgroups of ALK-positive patients.

A total of 276 patients were included in the study, spread across different treatment cohorts. In the treatment-naïve cohort (EXP1), 27 of 30 patients (90.0%; 95% CI 73.5-97.9). For patients who had received at least one ALK tyrosine kinase inhibitor (EXP2-5), 93 of 198 patients (47.0%; 39.9-54.2) achieved objective remission. In patients with measurable baseline CNS lesions, significant intracranial response rates were observed.

Safety analyses showed that the most common treatment-related adverse events were hypercholesterolemia and hypertriglyceridemia, but most were mild to moderate. A total of 19 patients (7%) experienced serious treatment-related adverse events, while 7 patients (3%) were permanently discontinued due to treatment-related adverse events. Importantly, no treatment-related deaths were reported.

Consistent with broad ALK mutation coverage and central nervous system penetration, lorlatinib demonstrated significant systemic and intracranial antitumor activity in patients with untreated ALK-positive non-small cell lung cancer and in patients who had progressed on treatment with crizotinib or other second-generation ALK tyrosine kinase inhibitors. Lorlatinib may be an effective option for first-line or follow-up treatment in patients with ALK-positive non-small cell lung cancer.