Pain Progression at Initiation of Cabazitaxel in Metastatic Castration-Resistant Prostate Cancer (mCRPC): A Post Hoc Analysis of the PROSELICA Study

SIMPLE SUMMARY: Despite the emergence of new therapies during the last decade, metastatic castration-resistant prostate cancer (mCRPC) remains fatal. Recent work showed that the timing of treatment initiation seems critical for patient outcomes. Thus, it is key to identify factors that can help in deciding when to start treatment. In the PROSELICA prospective international phase III trial (NCT01308580), mCRPC patients received cabazitaxel at two dose levels. We performed a retrospective analysis to determine what type of disease progression patients displayed at the cabazitaxel initiation and how this progression affected the patient’s clinical outcomes. Pain progression was associated with aggressive disease and shorter survival, compared to other progression types (rise in serum PSA levels and/or alterations observed on CT scan or bone scan). Systematic classification of patients enrolled in future phase III trials according to disease progression at treatment initiation may help further practitioners to determine the best timeline for treatment initiation. ABSTRACT: Background: In the PROSELICA phase III trial (NCT01308580), cabazitaxel 20 mg/m(2) (CABA20) was non-inferior to cabazitaxel 25 mg/m(2) (CABA25) in mCRPC patients previously treated with docetaxel (DOC). The present post hoc analysis evaluates how the type of progression at randomization affected outcomes. Methods: Progression type at randomization was defined as follows: PSA progression only (PSA-p; no radiological progression (RADIO-p), no pain), RADIO-p (±PSA-p, no pain), or pain progression (PAIN-p, ±PSA-p, ±RADIO-p). Relationships between progression type and overall survival (OS), radiological progression-free survival (rPFS), and PSA response (confirmed PSA decrease ≥ 50%) were analyzed. Results: All randomized patients (n = 1200) had received prior DOC, and 25.7% had received prior abiraterone or enzalutamide. Progression type at randomization was evaluable in 1075 patients (PSA-p = 24.4%, RADIO-p = 20.8%, PAIN-p = 54.8%). Pain progression was associated with clinical and biological features of aggressive disease. Median OS from CABA initiation or date of mCRPC diagnosis, all arms combined, was shorter in the PAIN-p group than in the RADIO-p or the PSA-p groups (12.0 versus 16.8 and 18.4 months, respectively, p < 0.001). In multivariate analysis, all arms combined, PAIN-p was an independent predictor of poor OS (HR = 1.44, p < 0.001). PSA response, rPFS, and OS were numerically higher with CABA25 versus CABA20 in patients with PAIN-p. Conclusions: This post hoc analysis of the PROSELICA phase III study shows that pain progression at initiation of CABA in mCRPC patients previously treated with DOC is associated with a poor prognosis. Disease progression should be carefully monitored, even in the absence of PSA rise.