Cabozantinib Active in CRPC; Demonstrates 'Dramatic and Rapid' Effects on Bone Scan Lesions

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(ChemotherapyAdvisor)–Cabozantinib (XL184), an orally bioavailable tyrosine kinase inhibitor with activity against MET and VEGFR2, has clinical activity in men with castration-resistant prostate cancer (CRPC), results of a study reported in the Journal of Clinical Oncology online as a Rapid Communication November 19.

In fact, “random assignment was halted early based on the observed activity of cabozantinib,” David C. Smith, MD, of the University of Michigan, Ann Arbor, MI, and colleagues stated.

The phase II discontinuation trial with an expansion cohort randomly assigned men with CRPC to cabozantinib 100mg/day or placebo. Median age of the patients was 68 years (range, 47-88 years).

Among those receiving cabozantinib, 72% had regression in soft tissue lesions and 68% of evaluable patients had improvement on bone scan, “including complete resolution in 12%,” Dr. Smith noted.

At 12 weeks, objective response rate (all partial responses) was 5% (n=9); 75% of patients (n=127) had stable disease. Median progression-free survival was 23.9 weeks (95% CI 10.7–62.4 weeks) with cabozantinib and 5.9 weeks (95% CI 5.4–6.6 weeks) with placebo (HR 0.12; P<0.001).

In 57% of evaluable patients, serum total alkaline phosphatase and plasma cross-linked C-terminal telopeptide of type I collagen were reduced by ≥50%. Retrospective analysis showed bone pain improved in 67% of evaluable patients, while narcotic use decreased in 56%. The most common grade 3 adverse events were fatigue (16%), hypertension (12%), and hand-foot syndrome (8%).

“This study demonstrates that cabozantinib has substantial antitumor activity in patients with advanced CRPC with manageable toxicity consistent with other tyrosine kinase inhibitors targeting multiple pathways,” the authors concluded, adding, “these results indicate a potential cooperative role for c-MET and VEGF signaling in the progression of CRPC and suggest that dual targeting of tumor and microenvironment may lead to an improved outcome for patients with CRPC.”

This study was supported by Exelixis, South San Francisco, CA.


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