Crizotinib Superior to Chemotherapy for Advanced ALK-Positive NSCLC

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Pasi A. Jänne, MD, PhD

Pasi A. Jänne, MD, PhD

Crizotinib demonstrated superiority to chemotherapy for the treatment of previously treated, advanced non-small cell lung cancer (NSCLC) with ALK rearrangement in a trial published online byThe New England Journalof Medicine on June 1.

Crizotinib is an oral tyrosine kinase inhibitor targeting the anaplastic lymphoma kinase (ALK) gene.

“This study demonstrates the value of testing lung cancer tissue for an ALK rearrangement, and it underscores the potential of cancer genomics to target cancer treatments to each patient," said Pasi A. Jänne, MD, PhD, director, Lowe Center for Thoracic Oncology of Dana-Farber Cancer Institute, and the study’s senior author, in a statement. “ALK now becomes the second abnormal gene that we are able to successfully target in lung cancer with drugs other than chemotherapy.”

In the phase III, open-label trial, crizotinib was compared to chemotherapy in 347 patients with locally advanced or metastatic ALK-positive NSCLC who had received one prior platinum-based treatment regimen. Patients were randomized to 250 mg of crizotinib, given orally, twice daily, or intravenous chemotherapy with 500 mg/m²pemetrexed or 75 mg/m²docetaxel every three weeks. Patients in the chemotherapy arm who had disease progression were permitted to cross over as a part of a separate study.

The median progression-free survival was 7.7 months in the crizotinib arm compared with 3.0 months in the chemotherapy arm (hazard ratio [HR] = 0.49, 95% CI, 0.37-0.64;P< .001). Response rates in the crizotinib arm were 65% (95% CI, 58-72) versus 20% in the chemotherapy arm (95% CI, 14-26;P< .001).

An interim analysis showed no significant improvement in overall survival versus chemotherapy (HR = 1.02; 95% CI, 0.68-1.54;P= .54).

Commonly reported adverse events in the crizotinib arm were visual disorder, gastrointestinal side effects, and elevated liver aminotransferase levels. Common adverse events for patients who received chemotherapy were fatigue, alopecia, and dyspnea.

Pfizer, Inc. provided financial support for the study.

Shaw AT, Kim DW, Nakagawa K, et al. Crizotinib versus chemotherapy in advanced ALK-positive lung cancer [published online ahead of print June 1 2013].N Engl J Med