Concomitant G-CSF use in maintaining an efficacious dose and safe delivery of docetaxel in combination with darolutamide in patients with metastatic hormone sensitive prostate cancer (mHSPC): ARASENS, a phase 3 study.

152 Background: In ARASENS, darolutamide (DARO) + androgen deprivation therapy (ADT) + docetaxel (DOC) significantly reduced risk of death by 32.5% vs placebo (PBO) + ADT + DOC in patients (pts) with mHSPC, with a similar incidence of treatment-emergent adverse events (TEAEs) between DARO and PBO treatment arms. DOC is associated with the risk of febrile neutropenia, which can be managed by DOC dose reduction and/or use of granulocyte colony stimulating factor (G-CSF). We report the impact of DOC dose intensity on the safety and efficacy of the ARASENS triplet regimen and evaluate the benefits of G-CSF use in maintaining effective dose and safe delivery of DOC. Methods: Pts were randomized to receive DARO 600 mg orally twice daily or PBO, with ADT + DOC. Baseline characteristics, G-CSF use, safety, overall survival (OS), and time to prostate-specific antigen (PSA) progression were analyzed according to DOC relative dose intensity (RDI; ≤85% vs >85%), defined as the ratio of DOC dose received vs protocol-defined full planned dose (75 mg/m 2 × 6 cycles). Results: Of the 1305 pts (DARO n=651; PBO n=654), 32 (2%) never received DOC or had no RDI data; 800 (60%) had DOC dose modifications. Of 1273 pts with DOC RDI data (DARO n=637; PBO n=636), >97% received an efficacious dose (RDI >80%), and use of DARO did not impact DOC RDI. Concomitant G-CSF was used in 48% (DARO) and 46% (PBO) of pts with DOC dose modifications vs 42% (DARO) and 45% (PBO) in the overall population, and was mainly used for secondary prophylaxis after first DOC dose in both the DOC dose modification population (DARO 184/186 [99%]; PBO 188/190 [99%]) and the overall population (DARO 269/272 [99%]; PBO 282/284 [99%]). G-CSF use was higher in pts with DOC RDI ≤85% (DARO 70%; PBO 74%) vs RDI >85% (DARO 39%; PBO 41%). Pt demographics and baseline disease characteristics were broadly similar between RDI ≤85% and >85% subgroups; >60% of pts with RDI ≤85% were from Asia Pacific. Incidences of grade ≥3 TEAEs/grade ≥3 neutropenia/grade ≥3 febrile neutropenia were higher with DOC RDI ≤85%, but DOC discontinuation rates were similar between RDI subgroups (≤85%: DARO 7%, PBO 11%; >85%: DARO 8%, PBO 11%). TEAEs leading to DOC dose modification were higher with DOC RDI ≤85% (DARO 93%; PBO 97%) vs RDI >85% (DARO 26%; PBO 25%). OS and time to PSA progression were similar between the RDI ≤85% and >85% subgroups within each treatment group. Conclusions: Appropriate DOC dose modification and G-CSF use allowed almost all pts (97%) to receive an efficacious dose of DOC, with no difference in OS and time to PSA progression for RDI ≤85% vs >85%. Addition of DARO to ADT + DOC did not increase DOC dose modification rates or G-CSF use. Clinical trial information: NCT02799602 .