Lindberg, Henriette

5054 Background: Rucaparib significantly improved radiographic progression-free survival (rPFS) versus physician’s choice of docetaxel or an androgen-receptor pathway inhibitor (ARPI) (abiraterone or enzalutamide) in men with BRCA mutations who were chemotherapy-naïve in the mCRPC setting and had received one prior ARPI in the phase 3 TRITON3 trial (NCT02975934). This post-hoc analysis evaluated whether the timing of prior ARPI therapy impacted the efficacy of rucaparib. Methods: Patients were randomized 2:1 to rucaparib (600 mg BID) or physician’s choice of docetaxel or ARPI, after progression on 1 prior second-generation ARPI in any setting. The primary endpoint was rPFS. Outcomes were analyzed according to whether patients received the prior ARPI in the metastatic castration sensitive (mCSPC) or castration resistant (mCRPC) setting. Data cutoff was August 25, 2022. Results: Of the 302 BRCA1/2 patients, 68 received prior ARPI in the mCSPC setting (42 rucaparib; 26 physician’s choice) and 234 in the mCRPC setting (159 rucaparib; 75 physician’s choice). Baseline characteristics were generally similar. Prior treatments in the mCSPC and mCRPC groups, respectively, included abiraterone (73.5% vs 53.0%), enzalutamide (29.4% vs 48.3%), and docetaxel (17.6% vs 24.8%). Median rPFS favored rucaparib over physician’s choice in both groups (mCSPC: 13.6 vs 8.2 months; HR 0.60 [95% CI, 0.32–1.15]; mCRPC: 11.2 vs 5.8 months; HR 0.43 [95% CI, 0.30–0.61]). Median OS was similar between treatments in both settings (mCSPC: 23.2 vs 21.7 months; HR 0.81 [95% CI, 0.47–1.41]; mCRPC: 23.2 vs 21.0 months; HR 0.91 [95% CI, 0.66–1.25]). Treatment-related adverse events occurred at comparable rates (89.6% vs 86.1%). Conclusions: Rucaparib demonstrated efficacy in patients with BRCA-mutated mCRPC, regardless of whether prior ARPI was administered in the mCSPC or mCRPC setting. Clinical trial information: NCT02975934 .

155 Background: Primary results from the randomized, multicenter, open-label, phase 3 TRITON3 (NCT02975934) study of rucaparib, a poly(ADP-ribose) polymerase inhibitor (PARPi) in patients with chemotherapy-naive mCRPC and BRCA1/2 (BRCA) vs the control arm of physician’s choice of DTX or ARPI (abiraterone acetate [ABI] or enzalutamide [ENZ]) demonstrated that rucaparib significantly improved radiographic progression-free survival (rPFS, primary efficacy endpoint) vs physician’s choice. Here, we report final OS and safety results from TRITON3. Methods: Patients with disease progression after 1 prior second-generation ARPI in any setting were randomized 2:1 to rucaparib 600 mg BID or physician’s choice of DTX, ABI, or ENZ (control). OS was a key secondary endpoint tested initially in the BRCA subgroup, followed by the intent-to-treat (ITT) population in an ordered step-down multiple-comparisons procedure. Crossover from placebo to rucaparib was allowed after radiographic progression was confirmed by independent radiology review. Results: As of March 1, 2024 (final analysis data cutoff),patients with BRCA (N = 302) and ATM (N = 103) alterations were randomized (ITT, N = 405). After an overall median follow-up of 44.0 months, median OS in the BRCA subgroup in the rucaparib arm was 23.2 months vs 21.2 months for the physician’s choice control arm (HR, 0.91 [95% CI, 0.68–1.20]; P = 0.5044; Table). Hierarchical testing did not continue due to lack of statistical significance. No OS benefit was observed in the ITT population or ATM subgroup (Table). Median duration of treatment in rucaparib and physician’s choice arms was 8.3 and 5.1 months, respectively. The most frequent any-grade treatment emergent adverse event (TEAE) in the rucaparib (n = 270) and physician’s choice (n = 130) arms was asthenia/fatigue (61.5% and 63.1%, respectively). The most frequent grade ≥3 TEAE was anemia (23.7%) with rucaparib, and asthenia/fatigue (9.2%) with physician’s choice. Of the 135 patients in the physician’s choice arm, 77 patients had radiographic progression and 70 crossed over to rucaparib. Conclusions: Rucaparib remains the only PARPi to show improved rPFS vs a DTX-containing control arm and has a similar OS even when most patients cross over to rucaparib. Safety was consistent with prior reports. These data support rucaparib as a treatment option for patients with BRCA-mutated mCRPC. Clinical trial information: NCT02975934 . Median OS at final analysis. Group Rucaparib, n Physician's choice, n Rucaparib, months Physician's choice, months HR (95% CI) a BRCA 201 101 23.2 21.2 0.91 (0.68–1.20) ITT 270 135 22.8 21.7 0.99 (0.78–1.26) ATM 69 34 18.4 22.1 1.21 (0.77–1.90) a Calculated by stratified Cox proportional hazard model.

AbstractBackgroundBladder cancer (BC) patients with advanced disease have poor outcomes. The use of patient‐reported outcomes (PROs) could lead to improvements in symptom management and hence quality of life (QoL). The aim of this study is to report correlations between selected PROs and QoL and thus to present symptoms that influence QoL. Identification of these symptoms during treatment can lead to earlier symptom management and thus secure improvements in QoL.MethodsBC patients in chemo‐ or immunotherapy for locally advanced or metastatic disease reported weekly PROs for the duration of their treatment. The PROs included EORTC QLQ‐C30 and QLQ‐BLM30 and 45 selected PRO‐CTCAE items. Spearman's correlation analysis was performed for all PRO‐CTCAE items and QLQ‐C30 global QoL and subdomains.ResultsIn this study, 78 BC patients reported 724 questionnaires. Spearman's analysis showed significant correlations between almost all PRO‐CTCAE items and the expected domain of QoL. The PRO‐CTCAE items with the strongest correlations with QoL were anxiety (F, frequency item) and emotional function (rs = −0.603, P < .0001), concentration (S, severity item) and cognitive function (rs = −0.704, P < .0001), discouraged (F) and emotional function (rs = −0.659, P < .0001), fatigue (S) and role function (rs = −0.659, P < .0001) and sad (F) and emotional function (rs = −0.711, P < .0001). The weakest correlations were found for the PRO‐CTCAE items urinary frequency, incontinence and urge, all with variations in the direction and significance of the correlations.ConclusionsThis study delivers information on which PROs may influence QoL for patients in clinical trials or daily clinic. Psychological issues have a strong impact on QoL and should be dealt with during treatment to secure the best possible QoL for BC patients.