Sanofi-aventis announced results from a phase-3 trial which demonstrated cabazitaxel, an investigational compound, plus prednisone/prednisolone significantly improved overall survival and progression-free survival in patients with metastatic (advanced) hormone-refractory prostate cancer whose disease progressed following treatment with docetaxel-based chemotherapy. The TROPIC trial compared the combination of cabazitaxel plus prednisone/prednisolone to the active agent mitoxantrone plus prednisone/prednisolone.

For many patients with metastatic hormone-refractory prostate cancer, their disease continues to progress despite prior chemotherapy. Currently, there are no approved therapies to treat these patients.

“These are significant results in the development of this investigational drug,” said Dr Oliver Sartor, North American principal investigator, Piltz professor for Cancer Research at Tulane Medical School, New Orleans. “Improved overall survival was demonstrated in this trial – and these are the first data to show a statistical improvement in overall survival in patients with this difficult-to-treat and aggressive form of prostate cancer.”

Tropic was designed to assess patients with metastatic hormone-refractory prostate cancer whose disease had progressed following treatment with docetaxel-based chemotherapy. Results showed that the combination of cabazitaxel and prednisone/prednisolone significantly reduced the risk of death by 30% [HR=0.70 (95% CI: 0.59-0.83); P<0.0001] with a clinically meaningful improvement in the median overall survival of 15.1 months in the cabazitaxel combination arm vs. 12.7 months in the mitoxantrone combination arm. Patients who received the combination treatment with cabazitaxel also experienced a significant increase in median progression-free survival [2.8 months vs. 1.4 months [HR=0.74 (95% CI: 0.64 - 0.86); P<0.0001].

The most frequent grade 3/4 hematological adverse events with cabazitaxel included neutropenia (81.7%), febrile neutropenia (7.5%) and infections (10.2%); the most frequent grade 3/4 non-hematological adverse events included nausea (1.9%), vomiting (1.9%) and diarrhea (6.2%). Most frequent treatment-emergent adverse events leading to discontinuation with the cabazitaxel arm were neutropenia (2.4%), hematuria (1.3%), diarrhea (1.1%) and fatigue (1.1%). Grade 3/4 peripheral neuropathy occurred in 0.5% patients in the cabazitaxel arm vs. 0.3% in the mitoxantrone arm. Deaths due to adverse events were 4.9% in the cabazitaxel arm (predominantly due to neutropenia and its complications) vs. 1.9% in the mitoxantrone arm.

“These are compelling results which we are looking forward to sharing with the health care and oncology community,” said Debasish Roychowdhury, senior vice president, Global Oncology, sanofi-aventis. “Providing new options and hope for patients with serious diseases, such as metastatic hormone-refractory prostate cancer, is what drives our ongoing commitment to researching and exploring novel anti-cancer compounds and to bringing these medicines to patients.”

Results will be presented by Dr Sartor in San Francisco, CA on March 5 at the 2010 Genitourinary Cancers Symposium sponsored by the American Society for Clinical Oncology (ASCO), the American Society for Radiation Oncology (ASTRO) and the Society of Urologic Oncology (SUO).

Cabazitaxel is a novel investigational taxane compound that may be active in cell lines refractory to taxanes.