Given, Robert

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]

TPS389 Background: Recent data have shown that up to 25% of patients with advanced prostate cancer, including mCRPC, have a deleterious germline or somatic mutation in BRCA1, BRCA2, ATM, or another homologous recombination DNA repair gene. Such mutations can be used as a molecular marker to select patients for targeted treatment with poly(ADP-ribose) polymerase inhibitors (PARPis), which are lethal to cells with HRD. Treatment with PARPis has shown preliminary evidence of antitumor activity in patients with mCRPC and a mutation in a homologous recombination DNA repair gene (Mateo et al. N Engl J Med. 2015;373:1697-708). These data provide a compelling rationale for evaluating rucaparib, a potent inhibitor of PARP1, PARP2, and PARP3, in patients with mCRPC associated with HRD. Methods: TRITON3 (NCT02975934) is a randomized, phase 3 study evaluating rucaparib 600 mg BID vs physician’s choice of abiraterone, enzalutamide, or docetaxel in patients with mCRPC and a deleterious germline or somatic BRCA1, BRCA2, or ATM mutation (identified by prior local testing or central testing during screening). Patients must have progressed on androgen receptor signaling–directed therapy in the mCRPC setting; prior PARPi treatment or chemotherapy for mCRPC are exclusion criteria. Patients will be randomly assigned in a 2:1 ratio to either rucaparib or physician’s choice, with the possibility for cross over from the comparator treatment to rucaparib upon radiographic progression confirmed by independent radiology review. The primary endpoint is radiographic progression-free survival (modified RECIST v1.1/PCWG3 criteria) assessed by independent radiology review. Secondary endpoints include objective response rate, duration of response, patient-reported outcomes, overall survival, and safety. Pretreatment blood samples collected from all patients will enable development of a noninvasive plasma-based companion diagnostic to select patients who may benefit from rucaparib treatment. Patients (≈400) will be enrolled at > 100 sites worldwide. Clinical trial information: NCT02975934.