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Positive Results Reported From Mid-Stage Trial of Cabozantinib (Cometriq) and Erlotinib (Tarceva) in Lung Cancer Patients

Cabozantinib achieves longer progression-free survival

Positive date have been reported from a randomized, phase II trial of cabozantinib (Cometriq, Exelixis, Inc.) and erlotinib (Tarceva, Genentech/Astellas Oncology), alone or in combination, as second- or third-line therapy in patients with stage-IV epidermal growth factor receptor (EGFR) wild-type non–small-cell lung cancer (NSCLC).

In Study E1512, 125 patients were randomly assigned to one of three treatment arms: erlotinib, cabozantinib, or the combination. During a pre-planned interim Safety Monitoring Committee analysis for futility, it was found that the trial met its primary endpoint of improving progression-free survival (PFS) with cabozantinib alone and with the combination of cabozantinib plus erlotinib compared with erlotinib alone, and the results were statistically significant. At the time of the analysis, the median follow-up period was 5.9 months, and overall survival data were immature.

Study E1512 was designed to enroll 117 patients with stage IV EGFR wild-type NSCLC who had received at least one prior chemotherapy. The patients were randomly assigned to receive erlotinib (150 mg daily), cabozantinib (60 mg daily), or erlotinib plus cabozantinib (150 mg plus 40 mg daily). The study’s objective was to determine whether single-agent cabozantinib or combination therapy including cabozantinib could extend PFS compared with single-agent erlotinib in this patient population. Secondary objectives included estimated overall survival, the best objective response, and toxicity.

The study had 91% power to detect a 50% reduction in the PFS hazard rate of 0.288 to 0.144, based on the estimated accrual and follow-up period. Assuming exponential survival, this corresponded to a 100% improvement in the median PFS of 2.4 months for erlotinib alone to 4.8 months for cabozantinib alone or for erlotinib plus cabozantinib.

Cabozantinib inhibits the activity of tyrosine kinases, including MET, RET, and vascular endothelial growth factors (VEGFRs). These receptor tyrosine kinases are involved in both normal cellular function and pathologic processes, such as oncogenesis, metastasis, tumor angiogenesis, and maintenance of the tumor microenvironment.

Comtriq (cabozantinib) is currently approved by the FDA for the treatment of progressive, metastatic medullary thyroid cancer. The product labeling includes a boxed warning regarding the potential for serious and sometimes fatal gastrointestinal perforations and fistulas, and for severe and sometimes fatal hemorrhage.

Source: Exelixis, Inc.; November 4, 2014.

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