[June 12, 2013] Exelixis announces encouraging data from Phase II prostate cancer trial Tweet Jun 12, 2013 (Datamonitor via COMTEX) -- Exelixis, Inc., a biotechnology company, has announced the updated interim data from 144 docetaxel-pretreated patients with metastatic castration-resistant prostate cancer, or mCRPC, and bone metastases treated with cabozantinib in an ongoing non-randomized expansion, or NRE, cohort of its Phase II randomized discontinuation trial. Median overall survival was 10.8 months in a patient population in which 73% of patients had received two or more prior therapies including docetaxel and abiraterone, enzalutamide, and/or cabazitaxel. Furthermore, a retrospective analysis of the interim data shows that early responses in bone scan, circulating tumor cell (CTC) levels, and pain are associated with longer median overall survival (OS) as compared to non-responders. These post hoc findings, particularly the bone scan response results, support the rationale for potential future prospective validation of the association of bone scan response with OS in Exelixis' ongoing Phase III COMET trials in mCRPC. "This clinical trial enrolled a heavily pretreated mCRPC population that has not been studied previously. These patients experienced disease progression despite treatment with docetaxel and additional therapies that included abiraterone, enzalutamide, or cabazitaxel. In this context the results are encouraging," said Dr Scher. "Patients with such advanced disease have limited options, and the data from this cohort suggest that cabozantinib has the potential to be an important treatment option for patients with mCRPC. The preliminary data suggest that these early response indicators are associated with longer median overall survival and warrant further prospective evaluation in Phase III. The ongoing Phase III trials will help to define the potential utility of cabozantinib in mCRPC." The interim results comprise data from 144 men with mCRPC in the NRE cohort of an ongoing Phase II randomized discontinuation trial. All patients had disease progression in either bone or soft tissue disease within 6 months of completion of docetaxel treatment, and the protocol differed from typical CRPC studies in that it excluded patients who progressed by PSA criteria alone, who generally have a better overall prognosis. All patients also had bone metastases on bone scan and 31% had measurable soft tissue disease. Seventy three percent of patients had received at least two prior lines of therapy for mCRPC, including docetaxel in all patients. In 36% of patients, disease progression was very rapid, occurring less than one month following the last dose of taxane therapy. Clinically significant pain, defined as baseline pain score by Brief Pain Inventory (BPI) greater than or equal to 4, was present in 47% of patients. Eighty percent of patients had a CTC count greater than or equal to 5/7.5 mL of blood. Patients received a 100 mg or 40 mg daily dose of cabozantinib. The median OS in the 144 patients was 10.8 months (95% confidence interval 9.1-13.0). Bone scan response (greater than or equal to 30% decrease from baseline in the Technetium-99m methylene diphosphonate bone scan lesion area determined by computer assisted detection) was observed in 65% of evaluable patients, CTC response (conversion from greater than or equal to 5 CTC/7.5 mL of blood to < 5 CTC/7.5 mL of blood) in 32% of evaluable patients, and pain response (greater than or equal to 30% decrease from baseline in worst pain observed at 2 consecutive assessments greater than or equal to 6 weeks apart) in 43% of evaluable patients. In univariate analyses, longer OS was associated with bone scan response at week 6, CTC response at week 6, and pain response. These findings were further examined and confirmed in sensitivity analyses after adjusting for significant baseline covariates, such as LDH, presence or absence of visceral metastasis, and bone scan lesion area (bone disease burden), which were selected from a stepwise Cox regression model. Across dose levels, the most common adverse events (AEs) of grade 3 or higher were fatigue, hypertension, and venous thrombosis. 25% of patients in the 40 mg dose cohort experienced one dose reduction due to an AE, and 84% of patients in the 100 mg dose cohort experienced at least one dose reduction due to an AE. Overall, the lower starting dose of 40 mg was better tolerated with lower rates of dose reduction and interruption. "These data provide additional evidence that cabozantinib has clinical activity against multiple aspects of metastatic disease in this patient population," said Michael M. Morrissey, Ph.D., president and CEO of Exelixis. "The overall survival results are encouraging given that the patients enrolled in the NRE cohort comprise a highly refractory and advanced mCRPC population, and are similar to those being enrolled in our ongoing Phase III COMET trials. We believe that these data provide continued support for our clinical strategy in this indication." http://www.datamonitor.com Republication or redistribution, including by framing or similar means, is expressly prohibited without prior written consent. Datamonitor shall not be liable for errors or delays in the content, or for any actions taken in reliance thereon [ Back To TMCnet.com's Homepage ]