Targeting PSMA in Prostate Cancer Treatment - Episode 8

Reviewing Data from the CARD Trial

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Tanya Dorff, MD, explains safety and efficacy data from the CARD trial.

Alicia Morgans, MD, MPH: Why don't we dive into another study that helps us understand what we can do after progression on 2 lines of therapy? This is the CARD trial. Tanya, can you walk us through that, please?

Tanya Dorff, MD: The CARD study looked at cabazitaxel vs a second AR [androgen receptor]-targeted drug in men with metastatic castrate-resistant prostate cancer which had progressed on an AR-targeted agent, and they could have had docetaxel or not. They were randomized to receive either cabazitaxel at the 25 mg per meter-squared [25 mg/m²] dose or the alternative AR agent, either ABI [abiraterone] if they had been on enzalutamide previously, or enzalutamide if they had been on ABI previously. The primary end point was radiographic progression-free survival, with key secondary end points, including overall survival as well as objective responses, pain response, skeletal events, and quality of life. This was a unique patient population in my view, because if you look at how they were progressing at the time of study entry, the bulk of the patients that get put on are progressing based on prostate-specific antigen [PSA] alone, and here about two-thirds were progressing in terms of pain. I would just put a caveat that this is not every prostate cancer patient. In terms of visceral metastases, it was below 20%, so in that way, it is quite representative. There was a good balance from the randomization in terms of how long the previous treatment had been effective. The radiographic progression-free survival was significantly better with cabazitaxel compared with the second AR-targeted agent. It was 8 months compared with 3.7 months, so it was a big difference—statistically significant—and a hazard ratio of 0.54. Looking at the subgroups, some subgroups were a little bit small—like the visceral subgroup—but generally speaking, the forest plot shows that cabazitaxel was really better for the various types of patients who were included. In terms of progression-free survival for cabazitaxel, it was 4.4 months median, and for the ABI or ENZA [enzalutamide] second AR-agent, it was 2.7 months. Again, very statistically significant. Overall survival was 13.6 months compared with 11 months, with a hazard ratio of 0.64. Although this was not as large a trial as VISION, I think this really did change practice, and hopefully, raised awareness that a second AR-targeted agent may not be the most effective strategy. This doesn't mean it's never a choice, but for someone who's a cabazitaxel candidate, this is really more effective. Now, one thing that people worry about when they're looking at cabazitaxel is tolerability. I think this trial was reassuring. There was a significant population of patients who were over 70 years old included in the trial, and yet the serious adverse events were really similar between the 2 arms. It was about 39%, whether you were on cabazitaxel or the second AR-targeted agent. Maybe we have to rethink how we view tolerability. Again, this was with the 25 mg/m² dosing. Of course, for patients who had up-front docetaxel and then maybe were just on castration maintenance, and then maybe got an AR targeted agent, you could reach for docetaxel as a rechallenge but I think the CARD data just really provide compelling evidence of the efficacy of this agent in this particular population.

Alicia Morgans, MD, MPH: Thank you for walking us through that and for thinking through the tolerability, particularly in our older patients, even at this 25 mg/m² dose. I think that's really, really important.

Transcript edited for clarity.