The U.S. Food and Drug Administration has approved the use of Xalkori (crizotinib) capsules for the treatment of patients with metastatic non-small cell lung cancer (NSCLC) whose tumors are anaplastic lymphoma kinase (ALK)-positive, as detected by an FDA-approved test.
The drug, made by Pfizer, had previously been granted accelerated approval in 2011 based on durable, objective response rates of 50 percent and 61 percent in two single-arm, open-label studies (OT 9/25/11). Accelerated approval allows for earlier approval of drugs that treat serious conditions, and that fill an unmet medical need based on a surrogate endpoint. After a drug receives accelerated approval, manufacturers are still required to conduct studies to confirm the drug's anticipated clinical benefit, known as Phase IV confirmatory trials, in order to receive traditional approval.
The drug's latest approval was based on an open-label, active-controlled, multinational, randomized trial of 347 patients with ALK-positive metastatic NSCLC, which showed superior progression-free survival and overall response rates for Xalkori-treated patients compared with patients receiving chemotherapy.
The patients in the trial had disease progression following platinum-based chemotherapy and had ALK expression in their tumors, which was detected by fluorescence in situ hybridization on central laboratory testing. Patients were randomized to receive either Xalkori or chemotherapy (pemetrexed or docetaxel if they had received prior pemetrexed).
The median progression-free survival for treatment with Xalkori was 7.7 months, compared with three months for patients treated with chemotherapy. The overall response rate was 65 percent for patients receiving Xalkori compared with 20 percent for patients receiving chemotherapy. Approximately 64 percent of the patients on the chemotherapy arm subsequently received Xalkori.
Common adverse reactions in the trials with Xalkori (occurring at rates of 25 percent or higher) included visual disorders, nausea, diarrhea, vomiting, constipation, edema, elevated transaminases, and fatigue. Safety data showed that serious adverse events were reported in 37 percent of the patients treated with Xalkori—the most common included: pneumonia, pulmonary embolism, dyspnea, and interstitial lung disease.
Fatal adverse reactions occurred in nine patients treated with the drug and included: acute respiratory distress syndrome, arrhythmia, dyspnea, pneumonia, pneumonitis, pulmonary embolism, interstitial lung disease, respiratory failure, and sepsis.
The recommended dose and schedule for Xalkori is 250 milligrams orally, twice daily, with or without food.