Safety and effectiveness of the radium‐223–taxane treatment sequence in patients with metastatic castration‐resistant prostate cancer in a global observational study (REASSURE)

Abstract Background Radium‐223 and taxane chemotherapy each improve survival of patients with metastatic castration‐resistant prostate cancer (mCRPC). Whether the radium‐223–taxane sequence could extend survival without cumulative toxicity was explored. Methods The global, prospective, observational REASSURE study (NCT02141438) assessed real‐world safety and effectiveness of radium‐223 in patients with mCRPC. Using data from the prespecified second interim analysis (data cutoff, March 20, 2019), hematologic events and overall survival (OS) were evaluated in patients who were chemotherapy‐naive at radium‐223 initiation and subsequently received taxane chemotherapy starting ≤90 days (“immediate”) or >90 days (“delayed”) after the last radium‐223 dose. Results Following radium‐223 therapy, 182 patients received docetaxel (172 95%) and/or cabazitaxel (44 24%); 34 patients (19%) received both. Seventy‐three patients (40%) received immediate chemotherapy and 109 patients (60%) received delayed chemotherapy. Median time from last radium‐223 dose to first taxane cycle was 3.6 months (range, 0.3–28.4). Median duration of first taxane was 3.7 months (range, 0–22.0). Fourteen patients (10 in the immediate and four in the delayed subgroup) had grade 3/4 hematologic events during taxane chemotherapy, including neutropenia in two patients in the delayed subgroup and thrombocytopenia in one patient in each subgroup. Median OS was 24.3 months from radium‐223 initiation and 11.8 months from start of taxane therapy. Conclusions In real‐world clinical practice settings, a heterogeneous population of patients who received sequential radium‐223–taxane therapy had a low incidence of hematologic events, with a median survival of 1 year from taxane initiation. Thus, taxane chemotherapy is a feasible option for those who progress after radium‐223. Clinical Trial Registration ClinicalTrials.gov identifier NCT02141438. Plain Language Summary Radium‐223 and chemotherapy are treatment options for metastatic prostate cancer, which increase survival but may affect production of blood cells as a side effect. We wanted to know what would happen if patients received chemotherapy after radium‐223. Among the 182 men treated with radium‐223 who went on to receive chemotherapy, only two men had severe side effects affecting white blood cell production (neutropenia) during chemotherapy. On average, the 182 men lived for 2 years after starting radium‐223 and 1 year after starting chemotherapy. In conclusion, patients may benefit from chemotherapy after radium‐223 treatment without increasing the risk of side effects.