255O - Darolutamide (DARO) in combination with androgen-deprivation therapy (ADT) and docetaxel (DOC) in Chinese patients (pts) with metastatic hormone-sensitive prostate cancer (mHSPC) in the phase III ARASENS study

Background

In China, DARO is approved in combination with ADT + DOC in pts with mHSPC, based on the ARASENS study in which DARO significantly improved overall survival (OS) vs placebo (PBO), with a favorable safety profile. We report the efficacy and safety of DARO in Chinese pts in ARASENS.

Methods

Pts were randomized 1:1 to receive DARO 600 mg twice daily or PBO with ADT + DOC. OS was the primary endpoint. Key secondary and exploratory endpoints included time to castration-resistant prostate cancer (CRPC), time to prostate-specific antigen (PSA) progression (≥25% increase from PSA nadir), PSA responses (undetectable PSA [<0.2 ng/mL], ≥90% PSA decrease from baseline [PSA90]), and safety (incidence/severity of treatment-emergent adverse events [TEAEs]).

Results

Of 1305 evaluable pts, 202 were from mainland China (DARO 104; PBO 98). Baseline characteristics were balanced between treatment groups and generally comparable to the overall population. In Chinese pts, DARO reduced the risk of death by 36.4% vs PBO (HR 0.64, 95% CI 0.41–0.99), even though a high proportion of pts who entered follow-up in the PBO group received subsequent life-prolonging therapy (DARO 29/49 [59.2%]; PBO 61/83 [73.5%]). Timfe to CRPC (HR 0.32, 95% CI 0.20–0.50) and time to PSA progression (HR 0.22, 95% CI 0.13–0.37) also favored DARO. More pts in the DARO vs PBO group achieved undetectable PSA (<0.2 ng/mL: 71.2% vs 19.4%) and PSA90 (87.5% vs 69.4%) at any time. Median treatment duration was longer with DARO vs PBO (41.1 vs 16.6 months), with similar proportions of pts in the two groups completing 6 cycles of DOC (DARO 82.9% vs PBO 79.2%) and requiring DOC dose modifications (68.6% vs 72.9%). Incidences of TEAEs were comparable between treatment groups; neutropenias (known toxicities of DOC) were the most common grade 3/4 TEAEs (DARO 63.8% vs PBO 61.5%; grade 3/4 febrile neutropenia 5.7% vs 2.1%, respectively).

Conclusions

In Chinese pts with mHSPC, DARO in combination with ADT + DOC improved OS, delayed time to CRPC and PSA progression, and demonstrated a similar safety profile to PBO with ADT + DOC, consistent with the overall ARASENS population.

Clinical trial identification

NCT02799602; June 15, 2016.

Editorial acknowledgement

Alex Morrison, OPEN Health Communications (London, UK).

Legal entity responsible for the study

Bayer AG.

Funding

Bayer AG and Orion Corporation.

Disclosure

M.R. Smith: Financial Interests, Personal, Advisory Board: Amgen, Astellas Pharma, Bayer, Janssen Oncology, Lilly, Novartis, Pfizer; Financial Interests, Personal, Research Funding, Paid to institution: Bayer; Financial Interests, Personal, Advisory Board, Paid to institution: ESSA, Janssen Oncology, Lilly, ORIC Pharmaceuticals. B. Tombal: Financial Interests, Personal, Advisory Board: Astellas Pharma, Bayer, Ferring, Janssen, Myovant, Pfizer/Astellas, Sanofi, Steba, Takeda; Financial Interests, Personal, Other, Honoraria: Amgen, Astellas Pharma, Janssen; Financial Interests, Personal, Other, Travel, accommodation, and expenses: Amgen, Astellas Pharma, Bayer, Ferring, Janssen, Sanofi. M. Hussain: Financial Interests, Personal, Advisory Board: AstraZeneca, Bayer, Convergent Therapeutics, GSK, Janssen, Merck, Novartis, Pfizer, Tempus; Financial Interests, Personal, Other, Honoraria: Astellas Pharma, AstraZeneca, Clinical Care Options, Great Debates and Updates in GU Oncology, Medscape Zero, Merck, Precisca, Targeted Oncology, UroToday; Financial Interests, Personal, Other, Patents, royalties, or other intellectual property: TITLE: SYSTEMS AND METHODS FOR TISSUE IMAGING, 3,676 Our File: Serial Number: UM-14437/US-1/PRO 60/923,385 UM-14437/US-2/ORD 12/101,753 US. 8,185,186 (US patent number) Systems and methods for tissue imaging (issued patent) EP 08745653.9 (EP application n; Financial Interests, Personal, Research Funding, Paid to institution: Arvinas, AstraZeneca, Bayer; Financial Interests, Personal, Advisory Board, Paid to institution: Genentech, PCCTC, Pfizer. Y. Niu, L. Cai, Q. Liu, N. Littleton, R. Li: Financial Interests, Personal, Other, Employment: Bayer. All other authors have declared no conflicts of interest.