Crizotinib (Xalkori), an inhibitor of the anaplastic lymphoma kinase (ALK) gene, has shown significant response rates in patients with advanced non–small-cell lung cancer (NSCLC) and the ALK rearrangement. One study in patients with ALK-positive advanced NSCLC showed a 60% objective response rate and a median PFS of 8.1 months with crizotinib; in a second study, the PFS was 9.7 months with crizotinib. A new study compared the response rates of crizotinib versus standard chemotherapy in patients with ALK-positive advanced NSCLC (Shaw AT, et al. N Engl J Med. 2013 Jun 1 [Epub ahead of print]).
This phase 3, open-label clinical trial included 374 patients with locally advanced or metastatic ALK-positive NSCLC who had previously received 1 platinum-based regimen. The patients were randomized in a 1:1 ratio to oral crizotinib 250 mg twice daily or to intravenous chemotherapy with pemetrexed (Alimta) 500 mg/m2 of body surface area or with docetaxel (Taxotere) 75 mg/m2 every 3 weeks. Patients receiving chemotherapy whose disease progressed were allowed to cross over to receive crizotinib as a separate study. The primary end point was PFS. Patients were screened from February 2010 through February 2012 for study eligibility. The prespecified number of progression events or death was reached in March 2012, and the data cutoff date was March 30, 2012.
The median PFS was 7.7 months with crizotinib versus 3.0 months with chemotherapy, with a hazard ratio for progression or death with crizotinib of 0.49 (P <.001). Overall response rates were 65% with crizotinib versus 20% with chemotherapy, a significant difference (P <.001). At the time of the data cutoff, the median follow-up for OS was similar between the 2 groups: 12.2 months in the crizotinib group and 12.1 months in the chemotherapy group. Also at that time, 49% of patients in the crizotinib group and 16% of patients in the chemotherapy group were still receiving therapy. Overall, 58 patients receiving crizotinib continued therapy beyond the predefined period of progression compared with 17 patients receiving chemotherapy, and the median therapy duration was 15.9 weeks with crizotinib versus 6.9 weeks with chemotherapy.
In general, patients reported greater reductions in symptoms of lung cancer, including chest pain, cough, and fatigue, and greater improvement in global quality of life with crizotinib than with chemotherapy.
