Patient reported outcomes (PRO) and tolerability of capivasertib (capi) plus abiraterone (abi) versus placebo (pbo) plus abi in patients (pts) with PTEN-deficient metastatic hormone-sensitive prostate cancer (mHSPC): CAPItello-281.

14 Background: An unmet need for targeted treatments exists for pts with PTEN deficient mHSPC. In the Phase 3 CAPItello-281 study (NCT04493853), capi+abi significantly improved radiographic progression-free survival vs pbo+abi in pts with PTEN deficient de novo mHSPC (HR 0.81 95% CI 0.66, 0.98; P =0.034). Here, we report on PRO and tolerability. Methods: Pts with PTEN deficient tumors (≥90% of viable malignant cells with no specific cytoplasmic staining by immunohistochemistry) received (1:1) capi or pbo with abi + prednisone/prednisolone and androgen deprivation therapy. Health-related quality of life (HRQoL) was assessed using the Functional Assessment of Cancer Therapy–Prostate (FACT–P) questionnaire. Clinically meaningful change thresholds: ±10 points for FACT-P total score and ±3 points for FACT-P physical wellbeing (PWB) and functional wellbeing (FWB) subscores. Common adverse events (AEs) related to AKT inhibition are summarized descriptively. Results: Of 1012 pts randomized to capi+abi (n=507) or pbo+abi (n=505), 503 in each arm received ≥1 dose; median (range) total treatment duration was 13.6 (0.1–46.6) vs 14.9 (0.1–47.1) months, 47.5% and 53.5% were ongoing capi or pbo. 60.9% and 62.8% in the capi+abi and pbo+abi arm completed the FACT-P. There were no clinically meaningful differences in least-squares mean change from baseline between arms in FACT-P total score (difference 0.4; 95% CI –1.97, 2.78), PWB (–0.4; 95% CI –0.89, 0.14) and FWB (–0.3; 95% CI –1.01, 0.37) subscores. Time to deterioration (TTD) in PWB was faster with capi+abi (HR 1.43 95% CI 1.15, 1.78); TTD in FACT-P total score and FWB showed no difference between arms (HR 1.10 95% CI 0.89, 1.37; HR 1.06 95% CI 0.86, 1.32). Most common AEs in the capi+abi arm occurred early and were manageable (Table). Conclusions: Common capi-associated AEs occur early and are clinically manageable. While pts in the capi+abi arm had more symptomatic AEs (eg diarrhea, rash) consistent with faster decline in self-reported PWB compared with pts in the pbo+abi arm, this did not affect other functional aspects of life (eg work, sleep) and overall HRQoL, allowing for continued treatment with capi+abi. Clinical trial information: NCT04493853 . Diarrhea Rash Hyperglycemia Capi+abi Pbo+abi Capi+abi Pbo+abi Capi+abi Pbo+abi Any grade AE, n (%) 261 (51.9) 40 (8.0) 178 (35.4) 35 (7.0) 191 (38.0) 65 (12.9) Median (IQR) time to onset, days 12 (3–43) 142 (28–339) 13 (11–43) 78 (37–195) 54 (15–114) 114 (71–326) Led to dose reduction, n (%) 22 (4.4) 0 43 (8.5) 2 (0.4) 33 (6.6) 1 (0.2) Led to dose interruption, n (%) 63 (12.5) 1 (0.2) 85 (16.9) 3 (0.6) 55 (10.9) 4 (0.8) Led to dose discontinuation, n (%) 5 (1.0) 0 24 (4.8) 0 5 (1.0) 0 Supportive txt given, n (%) 167 (33.2) 19 (3.8) 146 (29.0) 20 (4.0) 127 (25.2) 23 (4.6) Recovered/recovering, n (%) 238 (47.3) 36 (7.2) 164 (32.6) 28 (5.6) 140 (27.8) 43 (8.5)