Among patients with metastatic castration-resistant prostate cancer (mCRPC) who progressed within 12 months despite previous treatment with docetaxel and either abiraterone or enzalutamide (in either order), use of cabazitaxel as third-line treatment rather than switching patients to the other antiandrogen provides better outcomes, according to study results presented at the European Society for Medical Oncology 2019 Congress in Barcelona, Spain, and published concurrently in the New England Journal of Medicine.

Ronald de Wit, MD, of Erasmus Medical Center in the Netherlands, and colleagues compared these third-line treatments in the CARD trial (NCT02485691). The investigators randomly assigned 255 mCRPC patients who had previously received docetaxel and abiraterone or enzalutamide (both androgen-signaling-targeted inhibitors) to receive cabazitaxel (25 mg/m2 with prednisone and prophylactic granulocyte colony-stimulating factor), or the other androgen-signaling-targeted inhibitor. After a median follow-up duration of 9.2 months, the median imaging-based progression-free survival—the study’s primary outcome—was 8.0 months with cabazitaxel vs 3.7 months with the alternate antiandrogen. Cabazitaxel recipients had a significant 46% decreased risk of imaging-based progression or death compared with those treated with the alternate antiandrogen.

Median overall survival was also longer with cabazitaxel than with alternate antiandrogen (13.6 vs 11.0 months, respectively), corresponding to a significant 36% lower risk for death with cabazitaxel.

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PSA response occurred in 35.7% vs 13.5% of the cabazitaxel and alternate antiandrogen arms, respectively. Tumor response occurred in 36.5% vs 11.5%, and pain reduction occurred in 45.0% vs 19.3%.

Adverse events of grade 3 or higher occurred in 56.3% of patients receiving cabazitaxel and in 52.4% of those receiving the alternative antiandrogen. The investigators observed no new safety signals.

“The results of the CARD trial are in agreement with those of previous studies that have shown poor outcomes with a second androgen-signaling-targeted inhibitor,” Dr de Wit’s team wrote. “This is probably due to the fact that these agents target the same pathway and thus share common mechanisms of resistance. Conversely, taxanes, owing to their different mechanism of action, are able to overcome several mechanisms of resistance to androgen-signaling-targeted inhibitors, such as increased androgen-receptor signaling and PTEN (phosphatase and tensin homologue) loss.”

Cabazitaxel also might have greater intratumoral penetration than docetaxel in treatment-resistant tumors, the researchers noted.

In an interview with Renal & Urology News, Alicia K. Morgans, MD, MPH, of Northwestern University Feinberg School of Medicine in Chicago, who was not involved in the study, said the CARD findings are practice changing.

“Cabazitaxel offers men with mCRPC who experience progression on an AR [androgen receptor] targeted agent and docetaxel superior disease control than sequencing in an alternate AR directed therapy,” she said. “Physicians should no longer continue trying AR directed treatments after response and failure of an initial AR directed therapy. Urologists will need to partner with medical oncologists to provide this treatment option to patients, but multidisciplinary care ultimately will benefit patients, as will having access to all life-prolonging therapies available.”

The trial was sponsored by Sanofi, the makers of cabazitaxel (Jevtana®).

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de Wit R, de Bono J, Sternberg CN, et al. Cabazitaxel versus Abiraterone or enzalutamide in metastatic prostate cancer [published online September 30, 2019]. N Engl J Med. doi:10.1056/NEJMoa1911206