Phase II, Multicenter, Randomized Trial of Docetaxel plus Prednisone with or Without Cediranib in Men with Chemotherapy‐Naive Metastatic Castrate‐Resistant Prostate Cancer

LESSONS LEARNED. The negative results are consistent with the negative results of large phase III trials in which docetaxel plus antiangiogenic agents were used in patients with metastatic castrate‐resistant prostate cancer (mCRPC). The negative data underscore that, despite a sound biological rationale and supportive early‐phase clinical results, adding antiangiogenic agents to docetaxel for mCRPC is a great challenge. BACKGROUND. Inhibition of vascular endothelial growth factor (VEGF) signaling abrogates tumor‐induced angiogenesis to constrain tumor growth, and can be exploited therapeutically by using cediranib, an oral tyrosine kinase inhibitor of VEGF receptor signaling. Our preliminary phase I trial data showed that adding cediranib to docetaxel plus prednisone (DP) was safe and feasible, with early evidence for efficacy in patients with metastatic castrate‐resistant prostate cancer (mCRPC). METHODS. This multicenter phase II trial assessed whether adding cediranib to DP improves efficacy of DP in patients with mCRPC. Chemotherapy‐naive patients with mCRPC were randomly assigned to receive either docetaxel (75 mg/m(2) intravenously every 3 weeks) with prednisone (5 mg twice daily) plus cediranib (30 mg once daily; the DP+C arm) or DP only (the DP arm). The primary endpoint was to compare 6‐month progression‐free survival (PFS) rate between the two arms. Secondary endpoints included 6‐month overall survival (OS), objective tumor and prostate‐specific antigen (PSA) response rates, biomarkers, and adverse events. RESULTS. The 6‐month PFS rate in a total of 58 patients was only numerically higher in the DP+C arm (61%) compared with the DP arm (57%). Similarly, the 6‐month OS rate, objective tumor and PSA response rates, and biomarkers were not significantly different between the two arms. Increased baseline levels of interleukin 6 (IL‐6), however, were significantly associated with increased risk of progression. Neutropenia was the only grade 4 toxicity (38% in the DP+C arm vs. 18% in the DP arm). CONCLUSION. Combining cediranib with docetaxel + prednisone failed to demonstrate superior efficacy, compared with docetaxel + prednisone, and added toxicity. Our data do not support pursuing the combination further in patients with mCRPC.