The experimental drug cabozantinib achieved high rates of disease control and shrunk or eliminated bone metastases in a range of advanced cancers, according to results from a phase II trial.
The overall response rate was only 9%, but cabozantinib monotherapy was shown to stabilize disease after 12 weeks in 76% of participants with liver cancer, 71% of those with prostate cancer, and 58% of those with ovarian cancer. The drug achieved disease control rates of 45% in melanoma, 45% in breast cancer, and 40% in non–small cell lung cancer.
Moreover, cabozantinib surprised investigators by shrinking or eliminating bone metastases in 59 of 68 people who entered the study with bone metastases. This outcome was most pronounced in castrate-resistant prostate cancer, with "complete or partial bone scan resolution" in 86% of prostate cancer patients, lead author Dr. Michael S. Gordon said during a press briefing at which the American Society of Clinical Oncology (ASCO) offered a preview of studies to be presented at its annual meeting in June.
The study has been expanded to include more patients with castrate-resistant prostate cancer and with platinum-resistant or refractory ovarian cancer, and phase III trials are contemplated.
The findings suggest that cabozantinib, an oral tyrosine kinase inhibitor also known as XL184, may be effective across a range of solid tumors, possibly because of its action, which targets two pathways of tumor growth: vascular endothelial growth factor 2 (VEGF2) and MET.
"Cabozantinib demonstrated antitumor activity in 12 of 13 tumor types studied," said Dr. Gordon of Pinnacle Oncology Hematology in Scottsdale, Ariz. It also showed "unprecedented bone scan improvement," he added.
For their study, Dr. Gordon and his colleagues analyzed 398 patients with progressive measurable disease, and of whom 39% had bone metastases at enrollment.
All patients received cabozantinib 100 mg daily over 12 weeks in an open-label setting. At 12 weeks, patients with progressive disease (growth of 20% or more) were removed from the trial; patients with a partial response (shrinkage of 30% or more) stayed on the drug; and patients with stable disease were randomized to cabozantinib or placebo. This design, called a discontinuation trial, allows investigators to assess whether patients are "stable in spite or because of the drug," Dr. Gordon explained.
The findings on bone metastases were particularly striking, as they included patients with breast cancer, prostate cancer, and melanoma who experienced either partial or complete disappearance of the cancer on bone scans, often with improvement seen after 6 weeks of treatment. Improvement in bone scans was typically accompanied by relief of pain and less need for pain medications, a reduction in markers of bone reabsorption, and "sustained increases in hemoglobin in patients previously anemic," Dr. Gordon said.
The most common grade 3 or higher adverse events in the study were fatigue (9%), hand-foot syndrome (8%), and hypertension (5%). The discontinuation rate for adverse events was 12%.
Dr. Mark G. Kris, chief of the thoracic oncology service at Memorial Sloan-Kettering Cancer Center, New York, and chair of cancer communications for ASCO, commented at the press conference that the cabozantinib findings showed "an evolution in targeted cancer therapies" that go after "not just one pathway but the entire network."
"Here we are attacking multiple targets MET and VEGF, and we saw some very important tumor shrinkages," in common types of cancer, Dr. Kris said, along with benefits including stronger bones and less pain among patients with bone metastases.
The study was funded by Exelixis, the manufacturer of cabozantinib. Dr. Gordon said that he did not own stock in Exelixis or have other conflicts of interest. Several of his coauthors disclosed stock ownership in and/or employment with Exelixis.