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FDA Approves Lorlatinib for Metastatic ALK-Positive NSCLC

The FDA granted approval to lorlatinib (Lorbrena, Pfizer) for patients with anaplastic lymphoma kinase (ALK)-positive metastatic non-small cell lung cancer, according to a press release. 

In November 2018, the FDA granted lorlatinib accelerated approval for second or third-line treatment. 

The expanded first-line approval was based on data from the randomized, multicenter, open label phase 3 CROWN trial, which included 296 patients with ALK-positive metastatic NSCLC, who had not received prior systemic therapy for metastatic disease. 

Researchers randomly assigned patients 1:1 to receive lorlatinib 100 mg orally once daily (n=149) or crizotinib 250 mg orally twice daily (n=147). 

The study found significantly longer median progression-free survival as assessed by blinded independent central review in the lorlatinib arm (not estimable vs 9.3 months; HR = 0.28, 95% CI, 0.19-0.41). The FDA noted that overall survival data were immature.

Researchers also found significant responses with lorlatinib among patients with brain metastases. Among the 17 patients in the lorlatinib arm with measurable CNS lesions at baseline, the intracranial ORR was 82% compared with 23% among the 13 patients in the crizotinib arm. The duration of intracranial response was significantly longer in the lorlatinib group (79% vs 0%). 

"The CROWN data have shown [lorlatinib] can significantly improve outcomes in the first-line treatment of ALK-positive non-small cell lung cancer, including those that present with brain metastases," 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 adverse events included edema, peripheral neuropathy, weight gain, and cognitive effects, among others.

The FDA also approved the Ventana ALK (D5F3) CDx Assay (Ventana Medical Systems, Inc.) as a companion diagnostic for lorlatinib.


By Cassie Homer

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