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The patient described in the Presurvey had mCRPC with extensive bone and visceral metastases. The patient’s disease is symptomatic, and he has no actionable genetic mutations. His previous therapies include ADT alone, ADT plus enzalutamide, and docetaxel. Using these characteristics, all 5 experts would recommend cabazitaxel in our tool.
The FDA-approved agents in mCRPC include the AR signaling inhibitors abiraterone and enzalutamide, cytotoxic chemotherapy such as docetaxel and cabazitaxel, cellular-based immunotherapy agent sipuleucel-T, and the radiopharmaceutical radium-223. Additional agents are approved for mCRPC with specific types of mutations.
With so many agents available in mCRPC, a practical clinical question is how to best sequence these therapies, especially for later lines of therapy. The phase IV CARD study was designed to provide a clear answer to the question of whether to switch to the other AR inhibitor or to chemotherapy after disease progression on abiraterone or enzalutamide.
The randomized CARD trial enrolled patients with mCRPC who had previously received at least 3 cycles of docetaxel and experienced disease progression after ≤ 1 year on either abiraterone or enzalutamide. Patients were assigned to either cabazitaxel plus prednisone or the alternate AR-targeted therapy. Thus, if patients received previous enzalutamide, they would be switched to abiraterone, and vice versa. The primary endpoint was imaging-based PFS, and key secondary endpoints included OS.
Compared with switching to the alternate AR inhibitor, cabazitaxel was superior, with an improvement in median imaging-based PFS from 3.7 months to 8 months, with a HR of 0.54 and P < .001.
Cabazitaxel also significantly improved OS vs AR inhibitor switch, with a HR of 0.64 (P = .008) and an increase in median OS from 11 months to 13.6 months.
The results from the prospective CARD study are consistent with abundant single-institution data reporting that switching from one AR inhibitor to the other has a low response rate and short response duration.
The sequencing question is very important in mCRPC. The consequence of overlapping timelines of multiple FDA-approved therapies is that we have limited information on optimal sequencing of approved therapies. I think the CARD study, in combination with other data, strongly makes the case that a switch from one AR inhibitor to the other confers very limited benefit to patients. For patients who are candidates for additional chemotherapy after docetaxel and an AR inhibitor, the preferred choice would be cabazitaxel. There may be a role for switch therapy in selected patients, particularly patients who had a long period of benefit from the first AR pathway inhibitor, and in those who are not suitable candidates for second-line chemotherapy.
Now let’s revisit the polling question regarding one of our earlier patient cases.