On March 3, 2021, the FDA approved a new indication for lorlatinib (Lorbrena; Pfizer), a third-generation ALK inhibitor, for the first-line treatment of patients with non–small-cell lung cancer (NSCLC) and ALK mutation.
The FDA has previously approved lorlatinib based on the CROWN study for the second- or third-line treatment of patients with ALK-positive NSCLC, as detected by an FDA-approved test. This new indication also converts the previous accelerated approval to a full approval.
The expanded indication for lorlatinib was based on the results from the phase 3 CROWN clinical trial, which compared lorlatinib and crizotinib (Xalkori) in treatment-naïve patients with metastatic, ALK-positive NSCLC. The results showed a 72% reduction (hazard ratio, 0.28; 95% confidence interval, 0.19-0.41; P <.0001) in the risk for disease progression or death with lorlatinib versus crizotinib.
“The CROWN data have shown Lorbrena can significantly improve outcomes in the first-line treatment of ALK-positive non-small cell lung cancer, including those who present with brain metastases,” said Benjamin Solomon, MD, Department of Medical Oncology, Peter MacCallum Cancer Centre. “This approval is meaningful for my patients, because we now have a highly effective treatment option that can delay the progression of a typically aggressive disease.”
The most common (≥20%) adverse events of any grade with lorlatinib were edema, weight gain, peripheral neuropathy, cognitive effects, diarrhea, dyspnea, and hypertriglyceridemia. Treatment discontinuation because of adverse events occurred in 6.7% of people.