Medicine Matters oncology

Hello, I am Ronald de Wit. I am a Professor in medical oncology at the Erasmus University Medical Center in Rotterdam, the Netherlands. And I'm the lead investigator of the CARD study. The CARD study is an open label, randomized study, between cabazitaxel and either abiraterone or enzalutamide in patients who have previously been treated with docetaxel and either abiraterone or enzalutamide in any sequence.

Now, I think the key result is the radiographic progression free survival, which was robustly positive. The median radiographic progression free survival on cabazitaxel was 8 months, and on abi or enza, it was 3.7 months. So progression free survival was more than doubled. Hazard ratio 0.54-- statistically highly significant. 

We looked into the subgroups, a preplanned subgroup analysis, and that analysis showed that there was no impact of the sequence-- docetaxel first or after the AR targeted agent. And there was no impact of whether or not patients had been responding to prior AR targeted agent. So also the patients who had been responding to the AR targeted agent, and had progressed within 6 to 12 months, they did not do very well. And still, in that patient population, cabazitaxel was fairly superior.

Now, the superior efficacy also translated into a survival benefit. Median OS, on cabazitaxel, was 13.6 months, and on abi or enza it was 11 months. Hazard ratio 0.64. So there was a 36% reduction in the risk of death.

Interestingly, we also collected data on the post progression treatment-- that was not preplanned, but we had some information about post progression management. And a third of the patients who had been treated with abi or enza had been subsequently receiving cabazitaxel. And interestingly, that did not confound the survival benefit. And also of interest, 22% of the patients received palliative radiotherapy as the only treatment measure indicating that presumably these patients had become too frail. So I think this is a solid argument that we should not lose the opportunity of administering the most effective treatment.

In terms of side effects, it was quite well balanced. And the use of cabazitaxel plus G-CSF prophylaxis resulted in an incidence of neutropenic fever in only 3.2%.

So in conclusion, CARD reached the primary endpoint superior radiographic progression free survival more than doubled. Superior overall survival, a reduction in a risk of death by 36%, and a very manageable safety profile.

And I think this is going to change the treatment paradigm of crossing over between the AR targeted agents, which doesn't really make sense. And I think that we should use cabazitaxel earlier on and not keep on crossing off the AR targeted agents. Thank you.