A randomised, multicentre, phase II trial of active surveillance with or without six months of apalutamide for prostate cancer.

363 Background: Active surveillance (AS) is standard of care for low-risk and selected intermediate risk prostate cancer (PC). However, 20 to 50% of patients (pts) will ultimately require a local treatment following AS. This study aims to assess whether apalutamide (APA) could reduce the proportion of patients requiring local treatment within 3 years. Methods: Multicentric, open label, non-comparative phase II study conducted in pts with low to intermediate risk PC randomized between APA 6 months (240 mg/d) with AS vs AS alone. The primary objective was to evaluate the proportion (π) of patients requiring a local treatment in the APA+AS arm with the aim of rejecting the null hypothesis π ≥ 30% with a 5% significance level, using an exact one-sided test for proportions. The secondary objectives were to assess pathological progression (pPFS: Gleason score or a higher % of positive cores against baseline), PSA progression (bPFS: rise in PSA levels ≥ 25%/baseline) and APA safety. Results: Between 09/2017 and 07/2021 51 pts were randomized in APA group (gp) and 40 in control (CTRL) gp. The median follow up was 36 mo (95%CI [36-37]). Median (range) age, PSA and PSA density were respectively 64 yrs (47-76), 6.8 μg/L (1.4-19.9) and 0.13 μg/L/cm³ (0.024-0.38); only 2 pts had ISUP 2 PC and 92% were d’Amico low risk group. In the APA gp, 1 did not receive APA (consent withdrawal), 4 discontinued early (<2 months) for AE and 46 received 6 mo of APA. Local treatment was performed in 37 % (90%CI, [25-50]) in APA gp and the primary objective was not achieved (p=0.88). In CTRL gp, the proportion was 44% (90% CI: [30–58]), not significantly different from APA gp (p=0.66). At 36 mo, bPFS was 55% (95% CI: [39–69]) for the APA gp vs. 42% (95% CI: [26–57]) for the CTRL gp (p= 0.07) and pPFS was 32% (95% CI: 18–46) for the APA gp vs. 11% (95% CI: [4–24]) for the CTRL gp (p= 0.01). APA toxicities (TRAEs) were observed in 98% of pts, with 14% grade 3 (G3) and 4% serious TRAEs (2% G3). Skin toxicity was observed in 30% (4%G3), 56% had asthenia/fatigue (4%G3), hypertension in 18% (4%G3), gynecomastia 62%, breast or nipple pain 36%, thyroid dysfunction 12% (2%G3), diarrhea 10%, nausea 14%, elevated transaminases in 24%. Conclusions: Apalutamide for low risk prostate cancer did not significantly reduce the proportion of patients requiring local treatment within three years. However, the results indicate improved pPFS in the APA gp. There were no new safety concerns. Clinical trial information: NCT03088124 .