Cabazitaxel/Prednisone Combination Gets EU Marketing Approval

Becky McCall

March 25, 2011

March 25, 2011 (Vienna, Austria) — Cabazitaxel (Jevtana, Sanofi-Aventis) has been approved by the European Commission for use in combination with prednisone in the treatment of patients with metastatic hormone-refractory prostate cancer (mHRPC) previously treated with a docetaxel-containing regimen. The approval applies to 27 member states of the European Union, as well as Iceland, Lichtenstein, and Norway.

The news was announced here at the European Association of Urology (EAU) 26th Annual Congress, where a subanalysis of secondary end points from the phase 3 TROPIC (Treatment of Hormone-Refractory Metastatic Prostate Cancer Previously Treated With a Taxotere-Containing Regimen) trial was also presented, reigniting discussion about the drug. The European Commission approval follows a positive opinion from the Committee for Medicinal Products for Human Use of the European Medicines Agency in January, and approval by the US Food and Drug Administration and authorities in Brazil last year.

In the phase 3 TROPIC clinical study, presented at the American Society of Clinical Oncology 2010 annual meeting, as reported by Medscape Medical News, the cabazitaxel–prednisone combination was the first to show a significant survival benefit for patients with mHRPC.

TROPIC's initial findings showed that cabazitaxel, used as second-line therapy in mHRPC, increased survival by 28%, compared with standard-therapy mitoxantrone (Novantrone, OSI Oncology). Patients treated with cabazitaxel had a median survival of 15.1 months, compared with 12.7 months for patients receiving mitoxantrone — a statistically significant difference.

Stephane Oudard, MD, head medical oncologist from the Georges Pompidou European Hospital, Paris, France, and Bertrand Tombal, MD, from Clinique Unversitaire Saint Luc, Brussels, Belgium, said the recent European approval is good news for patients.

Dr. Oudard provided an overview of results to date that have been presented at previous meetings. "We have data that show that cabazitaxel improves overall survival, but now there are additional data on the mean overall survival, compared to the median overall survival. Median is useful for oncologists, but mean is useful for economists to make a complete analysis. These data showed that the mean overall survival is 18 months [with cabazitaxel], compared to 14 months [with mitoxantrone]."

Dr. Oudard also commented on the need to lower the occurrence of febrile neutropenia, which is higher with cabazitaxel. "This is important because if the treatment is working but the patient is suffering from febrile neutropenia, then it's not useful. By lowering neutropenia and febrile neutropenia, we would have a drug that is active and safe."

He added that cabazitaxel is now being tested as first-line therapy in a trial comparing cabazitaxel 25 or 20 mg/m2 with docetaxel to determine the incidence of neutropenia with a lower dose. "We might close one dosage arm if we see no difference. The patients in the TROPIC trial were highly treated with docetaxel, and they had a very low bone cell reserve."

During Dr. Tombal's presentation here at the EAU, he reported that "the goal of this poster is to investigate other end points; namely, objective tumor response, defined as disease control, in terms of partial response, complete response, or stable disease, which showed an advantage in favor of cabazitaxel."

In TROPIC, 405 men were evaluated for disease control, which was achieved in 61.7% of patients receiving cabazitaxel and 47.5% of those receiving mitoxantrone (P = .004).

The secondary end point was pain progression assessed by pain score (Eastern Cooperative Oncology Group criteria), decrease in pain intensity, and analgesic use. "There was no difference between men on cabazitaxel and mitoxantrone, and the pain score remained stable during treatment. A similar proportion of men experienced worsening in the 2 groups," Dr. Tombal told Medscape Medical News.

Session moderator N.A. Mottet, MD, a urologist from Clinique Mutualiste, in St. Etienne, France, asked whether cabazitaxel could be considered the standard of care for mHRPC in the light of these results. Dr. Tombal replied that he believes there is no standard of care.

"For me, the only standard of care is sitting with your colleague oncologists and radiation oncologists and using the armamentarium available. We need to take into account patient individuality and tailor treatment — whether abiraterone, or cabazitaxel, or whatever. It's like baseball; it's not until you have a home run that you win the game. It's a nice hit, but we need to keep searching," he replied.

Dr. Tombal added that chemotherapy is about extending survival. "What would be unacceptable is if extending survival comes with a deterioration of quality of life. We have to balance the 2 . . . and of course this is very difficult to measure."

The TROPIC study was supported by Sanofi-Aventis. Dr. Oudard reports associations with Sanofi-Aventis, Roche, and Pfizer. Dr. Tombal is a paid consultant for Sanofi-Aventis and a TROPIC study investigator. Dr. Mottet has disclosed no relevant financial relationships.

European Association of Urology (EAU) 26th Annual Congress; Poster 91. Presented March 21, 2011.