First results from a randomized phase II study of cabazitaxel (CBZ) versus an androgen receptor targeted agent (ARTA) in patients with poor-prognosis castration-resistant prostate cancer (mCRPC).

5059 Background: In the OSTRICh trial, poor-prognosis mCRPC patients were randomized between CBZ and ARTA, following progression on docetaxel (DOC) treatment. Methods: The OSTRICh trial is an open label, multicenter, phase IIb study. Patients with poor-prognosis mCRPC (visceral metastases AND/OR < 12 months responsive to androgen deprivation AND/OR progressing during or within 6 months after DOC completion), were randomized 1:1 between CBZ (25 mg/m 2 IV Q3W and prednisone 2 d 5 mg PO) and ARTA (daily abiraterone 1000 mg and prednisone 2 d 5 mg PO OR enzalutamide 160 mg PO). Life prolonging therapy between DOC and randomization was not allowed. Primary endpoint was to establish the Clinical Benefit Rate (no radiotherapy, no ECOG PS increase ≥2, no change of therapy AND no radiological progression) at 12 weeks (CBR) in the study arms, while formal comparison of the CBR was a secondary endpoint. A Fisher Exact test was used to assess differences in rates and a log rank test to assess differences in progression free and overall survival. All time to event endpoints were estimated with the Kaplan-Meier method and censored at last follow-up. Results: A total of 106 patients were randomized, 53 in each arm. Baseline median age was 70 (IQR 67-75) years and PSA 79.4 (IQR 29.0 - 160) ng/ml. ECOG PS score was 0/1 in 99 (93%) and 2 in 7 (7%) patients. Al patients fulfilled the criteria for poor-prognosis disease. Thirty-six (34%) patients received DOC in the metastatic hormone sensitive stage, while 41 (39%) previously received ARTA. Twenty-six of 43 evaluable patients in the CBZ arm had clinical benefit at 12 weeks (CBR: 60%, 95% CI: 44%-75%) and 20 of 39 (CBR: 51%, 95% CI: 35%-68%) in the ARTA arm (p = 0.50). At 12 weeks, 30 of 34 (88%, 95% CI: 73% - 97%) patients in the CBZ arm and 24 of 36 (67%, 95% CI: 49% - 81%) patients in the ARTA arm had no radiological progression (p = 0.046). After a median follow-up of 16.4 months (95% CI: 13.6–27.8), a serum PSA decrease ≥50% from baseline was established in 12 (23%, 95% CI: 12% - 36%) and 26 (49%, 95% CI: 35% - 63%)(p = 0.008) patients treated with CBZ and ARTA, respectively. Median radiological progression free survival (rPFS) was 6.0 months (95%CI: 4.11-14.5) in the CBZ arm and 5.8 months (95% CI: 5.22-10.2) months in the ARTA arm (p = 0.5), while median overall survival (OS) was 15.3 months (95%CI 9.49-22.4) and 13.8 months (95%CI 11.7-16.4) in CBZ and ARTA treated patients, respectively (p = 0.8). Grade ≥3 adverse events (AEs) occurred in 15 (29%) and 8 (15%) of patients treated with CBZ and ARTA, respectively. Conclusions: No significant difference in CBR was established between CBZ and ARTA treated patients. However, at 12 weeks significantly more CBZ treated patients had no radiological progression, while ≥50% PSA response rates were higher in ARTA treated patients. Clinical trial information: NCT03295565.