In having discussions with many men who have advanced prostate cancer it seems that the most common pattern of drug treatment sequencing for men with advanced, castration resistant prostate cancer after they have failed either of the second-line treatments of abiraterone (Zytiga) or enzalutamide (Xtandi) is either chemotherapy with docetaxel or the other second-line therapy. To translate this very long statement, men who have failed Zytiga will usually get either Xtandi or docetaxel and men who have failed Xtandi will often be offered docetaxel or Zytiga.

Is this the best sequencing pattern?

Evidence shows us that when the other 2nd line therapy is offered after the failure of one of the second-line treatments, there is limited or no benefit achieved. This sequencing pattern might not be the best option!

This observation is confirmed by recent results from the CARD trial that were presented during a Presidential Symposium at the European Society for Medical Oncology Congress 2019 and published online simultaneously in The New England Journal of Medicine there might be a superior option.

According to the presentation, after the failure of one of these second-line treatments (Zytiga or Xtandi), the administration of the third-line treatment of cabazitaxel (Jevtana) was superior to the use of another second-line treatment. Cabazitaxel was superior in extending progression-free survival and overall survival in men with metastatic castration-resistant prostate cancer who failed either Xtandi or Zytiga and docetaxel.

These results provide the first evidence from a randomized phase III trial that shows a superior survival benefit with this third-line therapy after the failure of Zytiga or Xtandi.

What the CARD STUDY tells us:

The CARD study confirmed that cabazitaxel should be offered as third-line therapy after docetaxel and abiraterone or enzalutamide in men with metastatic castration-resistant prostate cancer who are fit for chemotherapy.
Cabazitaxel extended survival as third-line therapy.
CARD is the first phase III study to show a survival benefit for third-line therapy in this setting.
The sequence of abiraterone or enzalutamide did not seem to matter.

This result should now inform clinical practice.

Cabazitaxel should be considered, in men who are still able to tolerate chemotherapy, after the failure of Xtandi or Zytiga and chemotherapy with docetaxel as opposed to another second-line treatment.

Third-Line Cabazitaxel Improves Outcomes in Patients With Metastatic Prostate Cancer