Men with castrate-resistant prostate cancer in whom docetaxel therapy fails may soon have a new treatment option, according to research presented at the 2010 Genitourinary Cancers Symposium in San Francisco, cosponsored by ASCO, the American Society for Therapeutic Radiology and Oncology, and the Society of Urologic Oncology. Results of the TROPIC trial, a double-blind, randomized phase III investigation of 755 men with castration-resistant prostate cancer whose disease progressed after treatment with a docetaxel-based regimen, indicated that the novel taxane cabazitaxel reduced the risk of death by 30% compared with mitoxantrone.

"Cabazitaxel will represent a new therapeutic option for these very difficult-to-treat patients," said lead researcher Oliver Sartor, MD, Piltz Professor for Cancer Research at Tulane Cancer Center in New Orleans. Dr. Sartor noted that treatments for men with metastatic prostate cancer who progress despite docetaxel are limited to supportive care, investigational agents, or hospice.

TROPIC Study

The TROPIC study (Treatment of Hormone-refractory Metastatic Prostate Cancer Previously Treated with a Taxotere-containing Regimen) is the first large randomized controlled trial to show an improvement in overall survival for men in whom docetaxel therapy fails. In the trial, conducted at 132 centers in 26 countries, patients were randomized to either cabazitaxel at 25 mg/m2 or mitoxantrone at 12 mg/m2 three times per week, and both groups received 10 mg/d of prednisone. The median overall survival for men who received cabazitaxel was 15.1 months, compared to 12.7 months for those who received mitoxantrone (HR = 0.70; 95% CI = 0.59-0.83; P ≤ .001). The median follow-up of patients was 12.8 months, although the trial lasted for 5 years. At the 2-year endpoint, cabazitaxel more than doubled survival compared to mitoxantrone.

Dr. Sartor pointed out that the patients enrolled in the trial had very advanced disease; more than half of patients had measurable disease, and almost 25% had visceral disease. The median time from their last docetaxel treatment to progression was less than 1 month, and patients had undergone a median number of 7.5 cycles of docetaxel.

Analysis of progression-free survival and response rates in both groups showed a significant advantage in the cabazitaxel arm. When the researchers looked at results in subgroups, such as patients who had been heavily treated with docetaxel or had progressed during their last docetaxel regimen, patients on cabazitaxel also survived longer.

As expected, the major serious adverse event in the cabazitaxel arm was neutropenia; 81.7% of those on cabazitaxel experienced grade 3/4 neutropenia vs 58% in the mitoxantrone arm. Rates of grade 3/4 febrile neutropenia in the cabazitaxel arm were 7.5% for cabazitaxel recipients vs 1.3% for those on mitoxantrone. Although the most common reason for death in the study was progressive disease, 18 deaths in the cabazitaxel arm resulted from adverse events-most from neutropenia. "This is an adverse event that needs to be anticipated and monitored carefully," Dr. Sartor said. Besides neutropenia, the most common adverse events in patients receiving cabazitaxel were diarrhea, fatigue, and asthenia.

Major Clinical Advance

Dr. Sartor noted that future clinical trials will be testing cabazitaxel in less advanced prostate cancers, and he anticipated that it may be investigated for other tumors as well. The findings from the TROPIC study will form the basis for submission to the FDA for approval of cabazitaxel, he added.

For more information on cabazitaxel and presentation of the final results of the TROPIC trial, watch for abstract 4508 on June 6 at the 2010 Annual Meeting.

Reference

1. Sartor AO, Oudard S, Ozguroglu M, et al. Cabazitaxel or mitoxantrone with prednisone in patients with metastatic castration-resistant prostate cancer (mCRPC) previously treated with docetaxel: Final results of a multinational phase III trial (TROPIC). 2010 Genitourinary Cancers Symposium. Abstract 9. Presented March 5, 2010.

Barbara Boughton is a freelance reporter based in the San Francisco area and coauthor of Reduce Your Cancer Risk.