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Crizotinib (Xalkori) Superior to Platinum-Based Chemotherapy in Phase III Lung Cancer Trial

Drug prolongs progression-free survival

Positive results from the PROFILE 1014 study have been published in the December 4 issue of the New England Journal of Medicine. The phase III trial evaluated the anaplastic lymphoma kinase (ALK) inhibitor crizotinib (Xalkori, Pfizer) in previously untreated patients with ALK-positive advanced non–small-cell lung cancer (NSCLC).

The results demonstrated that crizotinib 250 mg twice daily significantly prolonged progression-free survival (PFS) in previously untreated patients with ALK-positive advanced NSCLC compared with standard platinum-based chemotherapy regimens.

Crizotinib is indicated in the U.S. for the treatment of patients with NSCLC whose tumors are ALK-positive, as detected by an FDA-approved test. The U.S. indication is not limited to a specific line of therapy.

The PROFILE 1014 trial was a global, randomized, open-label, two-arm study evaluating the efficacy and safety of crizotinib in patients previously untreated for ALK-positive advanced NSCLC. A total of 343 patients were enrolled in the study. Approximately half of the patients were randomly assigned to the crizotinib arm, and the other half were assigned to the platinum doublet chemotherapy arm.

The study met its primary objective, with crizotinib significantly prolonging PFS in previously untreated patients with ALK-positive advanced NSCLC compared with standard platinum-based chemotherapy regimens (median PFS: 10.9 months vs. 7.0 months, respectively; hazard ratio, 0.45; P < 0.001). Crizotinib also demonstrated a significantly higher objective response rate compared with standard platinum-based chemotherapy regimens (74% vs. 45%, respectively; P < 0.001). Median overall survival was not reached in either treatment arm (hazard ratio, 0.82; P = 0.36).

The most commonly reported adverse events (AEs) with crizotinib were vision disorders (71%), diarrhea (61%), nausea (56%), and edema (49%). Most AEs were grade 1 or 2 in severity. Grade-3 or -4 elevations in aminotransferase levels occurred in 14% of patients in the crizotinib group and in 2% of patients in the chemotherapy group. These elevations were managed primarily with dose interruptions or dose reductions. Grade-3 or -4 neutropenia occurred in 11% and 15% of patients in the crizotinib and chemotherapy groups, respectively. No cases of febrile neutropenia were reported with crizotinib compared with two cases in the chemotherapy group.

NSCLC accounts for approximately 85% of lung cancer cases and remains difficult to treat, particularly in the metastatic setting. Approximately 75% of NSCLC patients are diagnosed late with metastatic (advanced) disease, where the 5-year survival rate is only 5%.

Source: Pfizer; December 3, 2014.


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