Real-World Cabazitaxel Use and Outcomes in Metastatic Castrate-Resistant Prostate Cancer: The Impact of Response to First ARPI

In metastatic prostate cancer, optimal sequence of therapies is uncertain. We retrospectively analyzed the treatments and responses of 592 such patients, finding poor response to a first androgen receptor pathway inhibitor helped identify those who appear to derive more benefit from cabazitaxel chemotherapy. Clinicians underutilized cabazitaxel over the study period. These real-world results can support clinician therapeutic decision making. Background: For post-docetaxel treatment of metastatic castrate-resistant prostate cancer (mCRPC), cabazitaxel has demonstrated superior third line PFS and OS compared to androgen receptor pathway inhibitors (ARPIs) in patients who progress within 12 months on first ARPI. The impact of first ARPI response, in particular responses beyond 12 months, on cabazitaxel outcomes in real-world populations is uncertain, as are other factors impacting cabazitaxel use. Materials and Methods: mCRPC patients in Alberta, Canada who received docetaxel from October 1, 2012 to December 31, 2017 were included. We reviewed mCRPC therapies, correlating cabazitaxel use with patient characteristics and TROPIC trial inclusion/exclusion criteria. OS and PFS were evaluated in patients who received cabazitaxel, stratified by time to progression on first ARPI = 12 months (poor ARPI responders, PAR) or >12 months (strong ARPI responders, SAR), using the Kaplan-Meier method. Results: PAR patients had inferior OS compared to SAR patients (12.3 vs. 24.8 months, P <.001). OS was longer in PAR patients receiving cabazitaxel compared to those not treated with cabazitaxel (16.9 vs. 10.3 months, P =.015), but this benefit was not seen in the SAR group (17.1 vs. 32 months, P =.084). Cabazitaxel use was associated with reduced PFS first line post-docetaxel in SAR (3.5 vs. 14.7 months, P <.001) but not PAR patients. Of 592 patients, 170 (29%) received cabazitaxel post-docetaxel, compared to 280 (47%) and 250 (42%) for abiraterone and enzalutamide. 238 patients (40%) did not have a discussion of cabazitaxel documented. Cabazitaxel use was increased in patients who fit TROPIC trial criteria (P <.001). Conclusions: In a real-world mCRPC cohort, cabazitaxel use was associated with longer OS among PAR patients, but crucially not among strong ARPI responders. Cabazitaxel was used less frequently and later than ARPIs post-docetaxel. These data help support first ARPI progression time as a consideration in treatment sequencing.