LBA25 - Final overall survival (OS) analysis from ARCHES: A phase III, randomized, double-blind, placebo (PBO)-controlled study of enzalutamide (ENZA) + androgen deprivation therapy (ADT) in men with metastatic hormone-sensitive prostate cancer (mHSPC)

Background

In ARCHES (NCT02677896), ENZA + ADT reduced risk of radiographic progression and improved secondary outcomes in men with mHSPC over PBO + ADT. Here we report the final OS (after 356 events), a key secondary endpoint in ARCHES and a critical benchmark of clinical efficacy, which was immature at the time of primary analysis.

Methods

Men with de novo or relapsed mHSPC (n=1150) were randomized 1:1 to ENZA (160 mg/day) + ADT or PBO + ADT, stratified by disease volume and prior docetaxel use. At the time of data cut-off and unblinding, 180 (31.3%) patients treated with PBO + ADT crossed over to open-label ENZA + ADT. A stratified log-rank test was performed at a two-sided significance level of 0.04 for OS based on an O’Brien-Fleming boundary. Kaplan-Meier estimates of OS and time to subsequent antineoplastic therapy (TTNAnti) were reported and hazard ratios (HRs) were estimated from a stratified Cox proportional hazards model. Safety was assessed via treatment-emergent adverse events.

Results

Baseline characteristics were similar between treatment arms. As of the data cut-off of May 28, 2021, 397 (34.5%) patients remained on treatment, with a median follow-up of 44.6 months). Median treatment duration was 40.2 months on ENZA + ADT, 13.8 months on PBO + ADT, and 23.9 months for crossover patients. ENZA + ADT extended survival vs PBO + ADT (HR 0.66; 95% confidence interval 0.53, 0.81; p<0.0001) [Table] with similar results in most prespecified subgroups. ENZA + ADT continued to prolong TTNAnti vs PBO + ADT. The safety profile of ENZA + ADT vs PBO + ADT was consistent with findings from the primary analysis.

Conclusions

This final analysis demonstrates that ENZA + ADT significantly prolongs survival in men with mHSPC and, together with the acceptable safety profile, supports the clinical benefit of ENZA + ADT in men with mHSPC. Table: LBA25

Time to event efficacy endpoints

CI, confidence interval; NR, not reached.Analyses include all randomized patients. OS was defined as time from randomization to death from any cause. For patients still alive at the date of the analysis cut-off point, OS was censored on the last date the patient is known to be alive.

Clinical trial identification

NCT02677896.

Editorial acknowledgement

This study was funded by Astellas Pharma Inc. and Pfizer Inc., the co-developers of enzalutamide. Medical writing and editorial assistance were provided by Folabomi Oladosu, PhD, and Jane Beck, MA, from Complete HealthVizion, funded by the study sponsors.

Legal entity responsible for the study

Astellas Pharma Inc. and Pfizer Inc., the co-developers of enzalutamide.

Funding

Astellas Pharma Inc. and Pfizer Inc.

Disclosure

A.J. Armstrong: Financial Interests, Personal, Other, Consultant: Astellas; Financial Interests, Personal, Invited Speaker: Janssen; Financial Interests, Personal, Advisory Board: Pfizer; Financial Interests, Personal, Advisory Board: AstraZeneca; Financial Interests, Personal, Invited Speaker: Bayer; Financial Interests, Personal, Invited Speaker: BMS; Financial Interests, Personal, Invited Speaker: Forma; Financial Interests, Personal, Advisory Board: Merck; Financial Interests, Personal, Advisory Board: Dendreon; Financial Interests, Institutional, Invited Speaker: Pfizer; Financial Interests, Institutional, Invited Speaker: Janssen; Financial Interests, Institutional, Invited Speaker: Beigene; Financial Interests, Institutional, Invited Speaker: BMS; Financial Interests, Institutional, Invited Speaker: Merck; Financial Interests, Institutional, Invited Speaker: Bayer; Financial Interests, Institutional, Invited Speaker: Astellas; Financial Interests, Institutional, Invited Speaker: Dendreon; Financial Interests, Institutional, Invited Speaker: Amgen. T. Iguchi: Financial Interests, Personal, Funding, Research Funding: Astellas, Bayer; Financial Interests, Personal, Advisory Role, Consulting or advisory: Astellas Pharma Inc., Bayer, Janssen; Financial Interests, Personal, Invited Speaker, Speakers Bureau: Astellas, Bayer, Janssen, Sanofi. A.A. Azad: Financial Interests, Personal, Other, Honoraria: Janssen, Astellas, Novartis, Tolmar, Amgen, Pfizer, Bayer, Telix Pharma, Bristol Myers Squibb, Merck Serono, AstraZeneca, Sanofi, Ipsen, Merck Sharp & Dohme, Noxopharm; Financial Interests, Personal, Advisory Role, Consulting or advisory: Astellas, Novartis, Janssen, Sanofi, AstraZeneca, Bristol Myers Squibb, Tolmar, Telix Pharma, Merck, Bayer, Ipsen, Merck Serono, Amgen, Noxopharm; Financial Interests, Personal, Funding, Research Funding: Astellas, Merck Serono, Novartis, Pfizer, Bristol Myers Squibb, Sanfi, AstraZeneca, GlaxoSmithKline, Aptevo Therapeutics, MedImmune, Bionomics, Synthorx, AstraZeneca, Ipsen; Financial Interests, Personal, Other, Travel, accomodations, expenses: Astellas, Sanofi, Merck Serono, Amgen, Janssen, Tolmar, Pfizer; Financial Interests, Personal, Invited Speaker, Speaker's Bureau: Astellas, Novartis, Amgen, Bayer, Janssen, Ipsen, Bristol-Myers, Merck Serono. R.Z. Szmulewitz: Financial Interests, Personal, Funding, Research Funding: AbbVie, Astellas Pharma, Incyte, Macrogenics, Janssen Oncology; Financial Interests, Personal, Other, Honoraria: stellas Pharma; Financial Interests, Personal, Advisory Role, Consulting or advisory: AstraZeneca, AbbVie, Exelixis, Merck, Amgen, Janssen Oncology, Sanofi, Astellas Pharma, PFizer; Financial Interests, Personal, Other, Travel, accomodations, expenses: Corcept Therapeutics. J. Holzbeierlein: Financial Interests, Institutional, Funding, Research Funding: MDxHealth; Financial Interests, Personal, Advisory Role, Consulting or advisory: Basilea; Non-Financial Interests, Personal, Other, Authorship: Astellas. A. Villers: Financial Interests, Personal, Advisory Role, Consulting or advisory: Astellas Pharam Inc; Financial Interests, Personal, Research Grant, Research Funding: Astellas Pharma Inc, Janssen Oncology. A. Alcaraz: Financial Interests, Personal, Advisory Role, Consulting or advisory: Astellas Pharma Inc; Financial Interests, Personal, Other, Travel, accomodations, expenses: Olympus, Ipsen, Janssen, Bayer. B.Y. Alekseev: Financial Interests, Personal, Funding, Research Funding: AstraZeneca, Merck, Sanofi, Bayer, Astellas Pharma, Janssen, Bristol Myers Squibb, Bavarian Nordic, Pfizer, ICON Clinical Research, Eisai, MSD, Roche; Financial Interests, Personal, Other, Honoraria: AstraZeneca, Astellas Pharma, Ferring, Eisai, Janssen, Bayer, MSD, Merck, Pfizer, Roche, Sanofi, Bristol Myers Squibb; Financial Interests, Personal, Advisory Role, Consulting or advisory: AstraZeneca, Astellas, Bayer, Bristol Myers Squibb, Ferring, Janssen, Merck, Sanofi, Pfizer, MSD, Roche, Eisai; Financial Interests, Personal, Other, Travel, accomodations, expenses: AstraZeneca, Astellas Pharma, Bayer, Bristol Myers Squibb, Janssen, MSD, Pfizer, Sanofi; Financial Interests, Personal, Invited Speaker, Speaker's Bureau: Janssen, Sanofi, Ferring, Astellas Pharma, Pfizer, AstraZeneca, Bayer, Merck, Bristol Myers Squibb, MSD, Eisai, Roche. N.D. Shore: Financial Interests, Personal, Advisory Role, Consulting or advisory: Bayer, Janssen Scientific Affairs, Dendreon, Tolmar, Ferring, Astellas/Medivation, Amgen, Pfizer, AstraZeneca, Genentech/Roche, Myovant Sciences, Astellas Pharma, AstraZeneca, Merck; Financial Interests, Personal, Invited Speaker, Speakers Bureau: anssen, Bayer, Dendreon. D.P. Petrylak: Financial Interests, Personal, Funding, Research Funding: Progenics, Sanofi, Endocyte, Genentech, Merck, Astellas, Novartis, AstraZeneca, Bayer, Lilly, Innocrin Pharma, MedImmune, Pfizer, Roche, Seattel Genetics, Clovis Oncology, Bristol Myers Squibb, Advanced Accelerator Applications, Agensys, BiXCell therapeu; Financial Interests, Personal, Ownership Interest, Stock or Ownership: Bellicum Pharmaceuticals, Tyme; Financial Interests, Personal, Expert Testimony: Celgene, Sanofi; Financial Interests, Personal, Other, Honoraria: AstraZeneca, Astellas Pharma, Ferring, Eisai, Janssen, Bayer, MSD, Merck, Pfizer, Roche, Sanofi, Bristol Myers Squibb; Financial Interests, Personal, Advisory Role, Consulting or advisory: Bayer, Exelixis, Pfizer, Roche, Astellas Pharma, AstraZeneca, Lilly, Amgen, Boehringer, Bristol Myers Squibb, Clovis Oncology, Incyte, Janssen, Pharmacyclics, Seattle Genetics, Urogen Pharma, Advanced Accelerator Applications, Ipsen, Bicycle Therapeutcs,. B. Rosbrook: Financial Interests, Personal, Full or part-time Employment, Pfizer employee: Pfizer. F. Zohren: Financial Interests, Personal, Full or part-time Employment, Pfizer employee: Pfizer; Financial Interests, Personal, Ownership Interest, Stock or Ownership: Pfizer, Allovir. S. Yamada: Financial Interests, Personal, Full or part-time Employment, Astellas Pharma employee: Astellas Pharma Inc. G.P. Haas: Financial Interests, Personal, Full or part-time Employment, Astellas Pharma employee: Astellas Pharma Inc. A. Stenzl: Financial Interests, Personal, Advisory Role, Consulting or advisory: psen, Roche, Janssen, Alere, Bristol Myers Squibb, Steba Biotech, Synergo, Ferring; Financial Interests, Personal, Funding, Research Funding: Karl Storz, Astellas Pharma, AstraZeneca , Medivation, Janssen, Johnson & Johnson, Roche, Cepheid, Immatics, Bayer, Novartis, Amgen, GenomeD; Financial Interests, Personal, Expert Testimony: GBA Pharma; Financial Interests, Personal, Other, Travel, accomodations, expenses: Janssen, Ipsen, Sanofi/Aventis, CureVac, Ferring, Astellas Pharma, Amgen, AstraZeneca.