Cabozantinib Shrinks Tumors and Bone Metastases in Prostate and Other Cancers || NCI Cancer Bulletin for May 31, 2011 - National Cancer Institute

Cabozantinib Shrinks Tumors and Bone Metastases in Prostate and Other Cancers

In a phase II clinical trial, the drug cabozantinib (or XL184) shrank tumors or halted their growth in patients with several types of solid tumors, including ovarian, liver, and prostate cancer. The drug also shrank bone metastases in patients with breast and prostate cancers and melanoma. Dr. Michael Gordon of Pinnacle Oncology Hematology in Scottsdale, AZ, presented the findings at a May 18 press briefing held in advance of the American Society of Clinical Oncology (ASCO) annual meeting.

Cabozantinib is a targeted therapy that blocks the action of the cell-signaling molecules hepatocyte growth factor receptor (MET) and vascular endothelial growth factor receptor 2 (VEGFR2) and may inhibit other signaling molecules as well. MET signaling can contribute to the growth and spread of cancer cells through the body (metastasis), and VEGFR2 plays a role in tumor blood vessel growth.

Of the 483 patients that Dr. Gordon and his colleagues enrolled in the trial, 398 were evaluated for tumor response during treatment. The trial employed a design called randomized discontinuation. All of the patients received cabozantinib for 12 weeks. Patients whose disease progressed during the first 12 weeks were removed from the trial, those whose tumors shrank remained on the drug, and those whose disease remained stable were randomly assigned to continue taking cabozantinib or a placebo to determine the drug's true role in stabilizing their disease.

The best results were seen in patients with liver, prostate, and ovarian cancer: 22 of 29 patients with liver cancer, 71 of 100 patients with prostate cancer, and 32 of 51 with ovarian cancer experienced either partial tumor shrinkage or stable disease.

Fifty-nine out of 68 patients who had bone metastases had their metastases shrink or disappear during the trial. Many of these patients experienced pain relief and a reduction in the need for narcotic pain medication.

These results show the benefit of "going after not just one pathway but…going after [an] entire network" of signaling molecules, stated Dr. Mark Kris, ASCO's Cancer Communications Committee chair, who moderated the press briefing.

Dr. Gordon explained that the drug's "exceptional activity" in shrinking metastases in patients with prostate cancer and the strong response among ovarian cancer patients led the researchers to expand the study to include 150 patients with each of those cancers in a nonrandomized arm of the trial. Results from those groups will be presented at the ASCO annual meeting next month in Chicago.

Also in the Journals: Cabozantinib May Shrink Some Rare Thyroid Tumors

In a phase I trial of cabozantinib, researchers led by Dr. Razelle Kurzrock of the University of Texas M. D. Anderson Cancer Center found that the targeted drug can shrink tumors in patients with metastatic medullary thyroid cancer (MTC) or MTC that could not be removed surgically. Results from 37 patients with advanced MTC treated with cabozantinib were published online May 23 in the Journal of Clinical Oncology.

Of the 35 patients whose tumors could be measured for response to the drug, 10 had tumors that shrank (a partial response). Fifteen of the 37 patients had tumors that remained stable for at least 6 months. Ninety percent of the 85 patients in the trial experienced at least one side effect, though almost half of those side effects were mild.

The partial responses seen in 10 of the patients "is remarkable…for a disease with essentially no conventional therapeutic options," wrote Drs. Yariv Houvras and Lori Wirth of Massachusetts General Hospital in an accompanying editorial. A phase III trial testing cabozantinib in patients with MTC is currently under way.

NCI Cancer Bulletin for May 31, 2011 - National Cancer Institute