Cabozantinib vs. Everolimus for Advanced Renal Cancer

Summary and Comment |
October 2, 2015

Cabozantinib vs. Everolimus for Advanced Renal Cancer

  1. Robert Dreicer, MD, MS, FACP, FASCO

Progression-free survival, the primary endpoint, was significantly longer with cabozantinib; incidence of grade 3 or 4 adverse events was higher.

  1. Robert Dreicer, MD, MS, FACP, FASCO

The tyrosine kinase inhibitor (TKI) cabozantinib targets vascular endothelial growth factor receptors (VEGFRs), MET, and AXL, all of which are up-regulated in renal cancer. The drug is currently FDA-approved for treating patients with metastatic medullary thyroid cancer, and it has demonstrated intriguing antitumor activity in patients with progressive renal-cell disease following therapy with VEGF and mammalian target of rapamycin (mTOR) inhibitors (Ann Oncol 2014; 25:1603).

Now, investigators have conducted an industry-sponsored, phase III, randomized, open-label trial to compare the efficacy of cabozantinib (60 mg daily) versus everolimus (10 mg daily) in 658 good-performance status patients who had advanced renal cancer with a clear cell component. All patients had progressed on at least one prior VEGFR-targeting tyrosine kinase inhibitor. Results were as follows:

  • The objective response rate was higher with cabozantinib than with everolimus (21% vs. 5%; P<0.001).

  • Median progression-free survival (the primary endpoint) was longer with cabozantinib than with everolimus (7.4 vs. 3.8 months; hazard ratio, 0.58; P<0.001).

  • A planned interim analysis indicated a trend toward longer overall survival with cabozantinib.

  • The incidence of grade 3 or 4 adverse events was 68% with cabozantinib and 58% with everolimus.

  • The most common adverse events leading to dose reductions with cabozantinib were diarrhea (16%), palmar–plantar erythrodysesthesia syndrome (11%), and fatigue (10%); three treatment-related deaths occurred, one in the cabozantinib arm and two in the everolimus arm.

Comment

As noted by editorialists, based on current data, cabozantinib is a salvage treatment for patients whose tumors progress during VEGF therapy. Limiting its use is the current lack of definitive survival data and its rather considerable toxicity profile, which led to dose reductions in >60% of patients. Ongoing studies may provide insight into whether cabozantinib is just another VEGFR TKI or something more.

Editor Disclosures at Time of Publication

  • Disclosures for Robert Dreicer, MD, MS, FACP, FASCO at time of publication Consultant / Advisory board Medivation; Genetech/Roche; Bind Pharmaceuticals; Astellas Editorial boards Urology; Clinical Genitourinary Cancer; Current Urology Reports Leadership positions in professional societies National Cancer Institute (Co-Chair, GU Oncology Steering Committee); American Board of Internal Medicine (member, Medical Oncology Test Writing Committee); Bladder Cancer Advocacy Network (member, scientific advisory board)

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