Cabozantinib linked to high rates of disease control, reduction of bone metastases

Cabozantinib effectively controlled advanced prostate, liver and ovarian cancers, tumors that are typically resistant to existing therapies, phase 2 results indicated.

The drug, an oral inhibitor of MET and VEGF receptor-2, also fully or partially eliminated bone metastases in patients with melanoma and breast and prostate cancers, said Michael S. Gordon, MD, a medical oncologist at Pinnacle Oncology Hematology in Scottsdale, Ariz. Gordon discussed the results during a press conference in advance of the 2011 ASCO Annual Meeting.

“Cabozantinib demonstrated antitumor activity in 12 of 13 tumor types studied,” he said. “We saw what we consider unprecedented bone scan improvement in the patients with prostate cancer, antitumor activity in ovarian cancer with an approximately 25% objective partial response rate at 12 weeks, leading to the expansion of these cohorts to identify more accurately the antitumor activity of this drug.”

There were 398 patients in the study evaluable for disease control, defined as partial response and stable disease, all of whom had advanced, progressive solid tumors, and 154 patients (39%) had bone metastases at baseline. All patients were assigned to 100 mg daily cabozantinib (Exelixis Inc.) for 12 weeks. Patients who had partial responses stayed on the drug, those with stable disease were randomly assigned to cabozantinib or placebo, and patients with progressive disease were removed from the trial.

Overall response rate was 9%. Researchers observed the highest disease control rates in liver cancer (76%), prostate cancer (71%) and ovarian cancer (58%).

Fifty-nine of 68 patients with bone metastases, including those with melanoma and breast and prostate cancers, had partial or complete disappearance of the cancer on bone scans. Gordon said many of those patients had significant pain relief as a result.

“A near complete resolution was seen in 86% of the prostate cancer patients enrolled in the trial. Typically, this was accompanied by a relief of pain and a reduction in the need for pain medications,” Gordon said. “Bone scan improvements are not limited to [prostate cancer], but were also seen in patients with bone cancer, melanoma, kidney cancer and thyroid cancer.”

Researchers have expanded the study to include more patients with castration-resistant prostate cancer because of the unexpected pain relief findings. Similarly, because of the high rate of lasting responses in ovarian cancer patients, researchers have also expanded the study to evaluate cabozantinib’s efficacy in platinum-resistant/refractory ovarian cancer, a particularly resistant form of the disease. – by Jason Harris

For more information:

Gordon MS. #3010. To be presented at: 2011 ASCO Annual Meeting; June 3-7, 2011; Chicago.

We see what are early signs of benefit by going after not just one pathway, but the entire network. We saw some very important tumor shrinkages, which, even more importantly, translated into benefit for patients — less pain, stronger bones. This kind of approach, which is encouraging theoretically, is also encouraging practically.

– Mark G. Kris, MD
Chair, ASCO Cancer Communications Committee

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