2019 Top Stories in Advanced Prostate Cancer: Cabazitaxel vs Abiraterone or Enzalutamide in Metastatic Prostate Cancer

[Balsam01]

My choice for top story this year is the phase III CARD trial published in The New England Journal of Medicine in late September of this year.1 The investigators showed an improvement in imaging-based progression-free survival with cabazitaxel versus an androgen signaling–targeted inhibitor (abiraterone or enzalutamide) in men who had previously been treated with docetaxel or the other androgen signaling–targeted inhibitor (ie, abiraterone or enzalutamide).

A total of 255 patients were randomized 1:1 to either cabazitaxel at 25 mg/m2 or to the androgen signaling–targeted inhibitor abiraterone at 1000 mg/day or enzalutamide at 160 mg/day.

The median imaging-based progression-free survival was 8.0 months with cabazitaxel and 3.7 months with the androgen signaling–targeted inhibitor (HR, 0.54; P<.001). Median overall survival was 13.6 months for cabazitaxel versus 11.0 months for the androgen signaling–targeted inhibitor (HR, 0.64; P=.008)

PSA response, defined as a reduction in the PSA level of at least 50% from baseline, confirmed by a second value obtained at least 3 weeks later, was 35.7% with cabazitaxel and 13.5% with the androgen signaling–targeted inhibitor (P<.001). There was improved tumor response with cabazitaxel; it was 37% in the cabazitaxel arm and 12% in the androgen signaling–targeted inhibitor arm (P=.004).

There were similar rates of serious adverse events in both groups: 38.9% with cabazitaxel and 38.7% with the androgen signaling–targeted inhibitor. However, there were more adverse events that lead to a discontinuation of therapy in the cabazitaxel group, 19.8% versus 8.9%. Disease progression as the reason for discontinuation was more frequent in the androgen signaling–targeted inhibitor group (71% vs 43.7%).

The authors address the dosing of cabazitaxel at 25 mg/m2 and cite the PROSELICA trial,2 which demonstrated noninferiority of cabazitaxel at 25 mg/m2 when compared with 20 mg/m2. I think it would be unlikely that there would have been a difference seen in this trial with the 20 mg/m2 dosing.

Based on this study in patients who have progressed on both docetaxel and an androgen signaling–targeted inhibitor, the better option for next-line therapy would be cabazitaxel over the other androgen signaling–targeted inhibitor.

Written by Brian E Lewis MD, MPH, FACP

Additional Info

References

Disclosures

1. de Wit R, de Bono J, Sternberg CN, et al. Cabazitaxel versus Abiraterone or Enzalutamide in Metastatic Prostate Cancer. N Engl J Med. 2019 Sep 30. doi:10.1056/NEJMoa1911206. [Epub ahead of print.]

2. Eisenberger M, Hardy-Bessard AC, Kim CS, et al. Phase III Study Comparing a Reduced Dose of Cabazitaxel (20 mg/m2) and the Currently Approved Dose (25 mg/m2) in Postdocetaxel Patients With Metastatic Castration-Resistant Prostate Cancer-PROSELICA. J Clin Oncol. 2017;35(28):3198-3206.