Conti, Peter S.

5048 Background: Ra-223, an alpha-emitting radionuclide, is the first agent of its kind approved for the treatment of mCRPC. Although a pivotal phase 3 study evaluated its short-term safety, there is a need to investigate its long-term safety. The REASSURE study prospectively examined the long-term safety of Ra-223, including secondary primary malignancies (SPMs), in a large patient (pt) population enrolled across Europe, the United States, Israel, and Latin America. Methods: We report final analyses (data cut-off Oct 24, 2024) of REASSURE (NCT02141438), a global, noninterventional study (enrolment 2014–2017). Primary outcomes were the incidence of SPMs, short- (30 days) and long-term (7 years) safety events, and bone marrow suppression (BMS) management in pts who had ≥1 Ra-223 dose. Secondary outcomes included overall survival (OS). Results: Analyses included 1472 pts; median follow-up was 17 months (range 0.3–95.4). Median age was 73 years and 80% of pts had an ECOG PS of 0/1. In evaluable pts, median alkaline phosphatase, prostate-specific antigen, and lactate dehydrogenase levels were 133 U/L, 59 ng/mL, and 266 U/L, respectively. Overall, 81% of pts had bone-only metastases at baseline; 19% of pts had metastases in the bone plus other sites (mostly lymph nodes). Prior treatments included abiraterone (48% of pts), enzalutamide (39%), docetaxel (39%), and cabazitaxel (9%). Pts received a median of 6 Ra-223 doses; 67% received ≥5 doses. SPMs occurred in 2% of pts (25 SPMs in 24 pts). Of these pts, 16 (67%) and 1 (4%) had received prior or concomitant radiotherapy, respectively. Overall, 3% of pts had drug-related serious adverse events >30 days after completing Ra-223. Fractures were reported in 10% of pts and were less common in pts with (7% of 605) than without (12% of 867) concomitant BHA use. During Ra-223 and up to 30 days after the last dose, there was no notable difference in the incidence of abnormal platelet counts between pts with (3%) or without (2%) prior chemotherapy; similar findings were seen for abnormal neutrophil counts (5% and 5%, respectively). BMS treatments, assessed from the start of Ra-223, were more common in pts who had received prior taxanes (38%) than in those who had not (26%). The most common life-prolonging therapies received after Ra-223 were docetaxel (18%), enzalutamide (15%), abiraterone (11%), and cabazitaxel (11%). Median OS was 15.6 months (95% CI, 14.6, 16.4); pt subgroups that survived the longest will be characterized and presented. Conclusions: This real-world safety analysis of pts with mCRPC is the longest follow-up of a radiopharmaceutical reported to date and supports the well-established favorable safety profile of Ra-223. The incidence of SPMs was low. The rate of fracture was low, especially in the presence of BHAs. Prior taxane chemotherapy use had no impact on hematological toxicity. Clinical trial information: NCT02141438 .

e17040 Background: Our aim was to evaluate two distinct clinical settings catering to US patients with metastatic castration-resistant prostate cancer (mCRPC): academic (A) and community (C) practice. We used data from a real-world non-interventional study (REASSURE; NCT02141438) examining the use of 223Ra. Methods: Patients with mCRPC who received at least one dose of 223Ra in the US were included. Enrolment occurred between 2014 and 2017; median follow-up was nearly 12 months. Our analysis included patient disease characteristics, treatment history, short- and long-term safety of 223Ra, patient overall survival (OS), and patient-reported pain (Brief Pain Inventory – Short Form [BPI–SF] scores). A clinically meaningful pain response was a ≥2-point decrease from a baseline score of ≥2 in the BPI-SF worst pain item during treatment until last dose. Results: Analysis included 498 patients (A: 147; C: 351). Comparing A with C, the median ages were 70 and 76 years, respectively, and the majority of patients (74% and 84%) had bone-only metastases. A higher percentage of patients in A (69%) than in C (49%) had completed at least one life-prolonging therapy (LPT) prior to 223Ra; these included abiraterone (A: 38%; C: 19%), enzalutamide (A: 32%; C:17%), docetaxel (A: 38%; C: 19%), and sipuleucel-T (A: 18%; C: 25%). Most patients received 5–6 223Ra injections in both settings (A: 65%; C: 71%). 223Ra was used concomitantly with LPTs in 48% of patients in A and 57% in C, predominantly with abiraterone (A: 25%; C: 25%) or enzalutamide (A: 25%; C: 36%); fewer patients in A (35%) received concomitant bone health agents than in C (52%). For safety outcomes, refer to the table. During treatment, 47% and 62% of patients with a baseline BPI-SF ≥2 had a clinically meaningful pain response in A and C, respectively. The median OS was 17.2 months (95% CI 14.0–19.4) in A and 18.4 months (14.8–21.0) in C. More patients in A (42%) than in C (26%) received a LPT after 223Ra, most commonly docetaxel (A: 25%; C: 12%). Conclusions: Patients treated in A tended to be younger and more heavily treated, as evidenced by a higher number of patients receiving LPTs prior to and following 223Ra treatment. Bone health agents were more frequently used in C. Additionally, more patients in C had a clinically meaningful pain response and more drug-related AEs were reported in A. Despite the observed differences, overall survival was comparable for both practice settings. Clinical trial information: NCT02141438 . [Table: see text]

Abstract Background: As the first radiolabled monoclonal antibody approved for the treatment for the treatment of cancer, yttrium 90 (90Y) ibritumomab tiuxetan (Zevalin®) achieves both high response rates and durable remissions in patients with relapsed or refractory, low-grade, follicular, or transformed B-cell NHL. Because of the stability of 90Y ibritumomab tiuxetan and its favorable pharmacokinetic profile (ie, predictable urinary clearance and absence of dehalogenation), dosing is based on patient weight and platelet counts. Yttrium 90 ibritumomab tiuxetan is typically delivered at a dose of 0.4 mCi/kg (in patients with platelets >150,000/mm3) or 0.3 mCi/kg (in patients with platelets ≤150,000/mm3) to a maximum recommended dose (MRD) of 32 mCi. However, patients >80 kg with platelet counts exceeding 150,000/mm3 may receive a lower drug concentration (ie, <0.4 mCi/kg 90Y) as a result of dose capping. We evaluated whether the 32 mCi dose cap influences the safety or efficacy of ibritumomab tiuxetan therapy in patients >80 kg. Methods: Efficacy and safety data were collected for patients from 3 registrational trials that received either 0.4 mCi/kg 90Y (patients ≤80 kg) or 32 mCi 90Y (patients >80 kg). Results: Clinical responses in 170 patients were evaluated. Patients ≤80 kg (n = 103) had a median weight of 70 kg (range, 45–80 kg) versus a median weight of 95 kg (range, 81–159) for patients >80 kg (n = 67). Gender (41% M vs 73% M, respectively; P <.01) was the only significantly different baseline characteristic between the ≤80 kg and >80 kg groups. Similar efficacy and safety results were reported for both subsets of patients. Overall response rates of 79% and 70% were observed for patients ≤80 kg and >80 kg, respectively (P =.27); and no significant differences were seen in complete response rates (28% vs 34%, respectively; P =.40). Median TTP (8.9 months vs 9.5 months; P =.53) and median DR (8.5 months vs 11.5 months; P =.34) were equivalent between the 2 weight-based groups. In addition, there were no statistically significant differences in safety measures including grade 3/4 nonhematologic adverse events, neutropenia, thrombocytopenia, or anemia. Conclusions: As a consequence of dose capping at an MRD of 32 mCi, 39% of patients received a lower dose/kg of 90Y ibritumomab tiuxetan. However, despite the difference in dose administered on a unit of body weight basis, the efficacy and safety results were similar between patients ≤80 kg and >80 kg. We conclude that the 32 mCi dose cap does not influence the efficacy or safety profile of 90Y ibritumomab tiuxetan for patients >80 kg.