Lorbrena New Treatment Approved for Patients with Metastatic NSCLC and ALK Mutation

December 2018, Vol 9, No 4 - FDA Approvals, News & Updates


On November 2, 2018, the FDA accelerated the approval of lorlatinib (Lorbrena; Pfizer) as second- or third-line treatment for patients with metastatic non–small-cell lung cancer (NSCLC) and ALK mutation whose disease progressed during crizotinib (Xalkori) treatment and at least 1 more ALK inhibitor or during alectinib (Alecensa) or ceritinib (Zykadia) therapy as the first ALK inhibitor therapy. The FDA used its priority review for this approval and granted lorlatinib a breakthrough therapy designation.

This approval was based on a nonrandomized, dose-ranging, multicohort, multicenter study; the results came from a subgroup analysis of 215 patients with metastatic NSCLC and ALK mutation who received at least 1 ALK inhibitor. The major efficacy measures were overall response rate (ORR) and intracranial ORR.

The ORR was 48% (95% confidence interval [CI], 42-55), with 4% complete responses and 44% partial responses. The estimated median response duration was 12.5 months (95% CI, 8.4-23.7). The intracranial ORR in 89 patients with measurable central nervous system lesions was 60% (95% CI, 49-70), with 21% complete responses and 38% partial responses. The estimated median response duration in this subgroup was 19.5 months (95% CI, 12.4-not reached).

The most common (≥20%) adverse events with lorlatinib were edema, peripheral neuropathy, cognitive effects, dyspnea, fatigue, weight gain, arthralgia, mood effects, and diarrhea. The most common laboratory abnormalities were hypercholesterolemia and ­hypertriglyceridemia.