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Randomized Controlled Trial
. 2022 May 20;40(15):1616-1622.
doi: 10.1200/JCO.22.00193. Epub 2022 Apr 14.

Improved Survival With Enzalutamide in Patients With Metastatic Hormone-Sensitive Prostate Cancer

Andrew J Armstrong  1 , Arun A Azad  2   3 , Taro Iguchi  4 , Russell Z Szmulewitz  5 , Daniel P Petrylak  6 , Jeffrey Holzbeierlein  7 , Arnauld Villers  8 , Antonio Alcaraz  9 , Boris Alekseev  10 , Neal D Shore  11 , Francisco Gomez-Veiga  12   13 , Brad Rosbrook  14 , Fabian Zohren  14 , Shunsuke Yamada  15 , Gabriel P Haas  15 , Arnulf Stenzl  16
Affiliations
Randomized Controlled Trial

Improved Survival With Enzalutamide in Patients With Metastatic Hormone-Sensitive Prostate Cancer

Andrew J Armstrong et al. J Clin Oncol. .

Abstract

Clinical trials frequently include multiple end points that mature at different times. The initial report, typically based on the primary end point, may be published when key planned co-primary or secondary analyses are not yet available. Clinical Trial Updates provide an opportunity to disseminate additional results from studies, published in JCO or elsewhere, for which the primary end point has already been reported.In primary analysis, enzalutamide plus androgen deprivation therapy (ADT) improved radiographic progression-free survival (rPFS) in patients with metastatic hormone-sensitive prostate cancer (mHSPC); however, overall survival data were immature. In the phase III, double-blind, global ARCHES trial (ClinicalTrials.gov identifier: NCT02677896), 1,150 patients with mHSPC were randomly assigned 1:1 to enzalutamide (160 mg once daily) plus ADT or placebo plus ADT, stratified by disease volume and prior docetaxel use. Here, we report the final prespecified analysis of overall survival (key secondary end point) and an update on rPFS, other secondary end points, and safety. After unblinding, 180 (31.3%) progression-free patients randomly assigned to placebo plus ADT crossed over to open-label enzalutamide plus ADT. As of May 28, 2021 (median follow-up, 44.6 months), 154 of 574 patients randomly assigned to enzalutamide plus ADT and 202 of 576 patients randomly assigned to placebo plus ADT had died. Enzalutamide plus ADT reduced risk of death by 34% versus placebo plus ADT (median not reached in either group; hazard ratio, 0.66; 95% CI, 0.53 to 0.81; P < .001). Enzalutamide plus ADT continued to improve rPFS and other secondary end points. Adverse events were generally consistent with previous reports of long-term enzalutamide use. In conclusion, enzalutamide plus ADT significantly prolongs survival versus placebo plus ADT in patients with mHSPC.

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Conflict of interest statement

Andrew J. ArmstrongConsulting or Advisory Role: Bayer, Dendreon, Pfizer, Astellas Scientific and Medical Affairs Inc, AstraZeneca, Merck, Bristol Myers Squibb, Janssen, FORMA Therapeutics, Novartis, Exelixis, Myovant Sciences, GoodRxResearch Funding: Dendreon (Inst), Bayer (Inst), Pfizer (Inst), Novartis (Inst), Janssen Oncology (Inst), Astellas Pharma (Inst), Gilead Sciences (Inst), Roche/Genentech (Inst), Bristol Myers Squibb (Inst), Constellation Pharmaceuticals (Inst), Merck (Inst), AstraZeneca (Inst), BeiGene (Inst), Bristol Myers Squibb (Inst), Amgen (Inst), FORMA Therapeutics (Inst)Patents, Royalties, Other Intellectual Property: Circulating tumor cell novel capture technology (Inst)Travel, Accommodations, Expenses: Astellas Scientific and Medical Affairs Inc Arun A. AzadHonoraria: Janssen, Astellas Pharma, Novartis, Tolmar, Amgen, Pfizer, Bayer, Telix Pharmaceuticals, Bristol Myers Squibb, Merck Serono, AstraZeneca, Sanofi, Ipsen, Merck Sharp & Dohme, Noxopharm, Aculeus TherapeuticsConsulting or Advisory Role: Astellas Pharma, Novartis, Janssen, Sanofi, AstraZeneca, Pfizer, Bristol Myers Squibb, Tolmar, Telix Pharmaceuticals, Merck Sharp & Dohme, Bayer, Ipsen, Merck Serono, Amgen, Noxopharm, Aculeus TherapeuticsSpeakers' Bureau: Astellas Pharma, Novartis, Amgen, Bayer, Janssen, Ipsen, Bristol Myers Squibb, Merck SeronoResearch Funding: Astellas Pharma, AstraZeneca, Merck Serono, Merck Serono (Inst), Novartis (Inst), Pfizer (Inst), Bristol Myers Squibb (Inst), Sanofi (Inst), AstraZeneca (Inst), GlaxoSmithKline (Inst), Aptevo Therapeutics (Inst), MedImmune (Inst), Bionomics (Inst), Synthorx (Inst), Astellas Pharma (Inst), Ipsen (Inst), Lilly (Inst), Gilead Sciences (Inst), Janssen (Inst), Exelixis (Inst), MSD (Inst)Travel, Accommodations, Expenses: Astellas Pharma, Sanofi, Merck Serono, Amgen, Janssen, Tolmar, Pfizer Taro IguchiConsulting or Advisory Role: Astellas Pharma, BayerSpeakers' Bureau: Astellas Pharma, Bayer Yakuhin, Janssen, Sanofi, AstraZeneca, TakedaResearch Funding: Astellas Pharma, Bayer Yakuhin Russell Z. SzmulewitzHonoraria: Astellas PharmaConsulting or Advisory Role: AstraZeneca, AbbVie, Exelixis, Merck, Amgen, Janssen Oncology, Sanofi, Astellas Pharma, PfizerResearch Funding: AbbVie (Inst), Astellas Pharma (Inst), MacroGenics (Inst), Janssen Oncology (Inst), Plexxikon (Inst), Harpoon Therapeutics (Inst), Merck (Inst), Novartis (Inst)Patents, Royalties, Other Intellectual Property: Patent licensed by The University of Chicago, of which I am a coinventor to Corcept Therapeutics for combination AR/GR inhibition in prostate cancerTravel, Accommodations, Expenses: Corcept Therapeutics Daniel P. PetrylakStock and Other Ownership Interests: Bellicum Pharmaceuticals, TYMEConsulting or Advisory Role: Bayer, Exelixis, Pfizer, Roche, Astellas Pharma, AstraZeneca, Lilly, Amgen, Boehringer Ingelheim, Bristol Myers Squibb, Clovis Oncology, Incyte, Janssen, Pharmacyclics, Seattle Genetics, UroGen Pharma, Advanced Accelerator Applications, Ipsen, Bicycle Therapeutics, Mirati Therapeutics, Monopteros Therapeutics, Regeneron, Gilead SciencesResearch Funding: Progenics (Inst), Sanofi (Inst), Endocyte (Inst), Genentech (Inst), Merck (Inst), Astellas Medivation (Inst), Novartis (Inst), AstraZeneca (Inst), Bayer (Inst), Lilly (Inst), Innocrin Pharma (Inst), MedImmune (Inst), Pfizer (Inst), Roche (Inst), Seattle Genetics (Inst), Clovis Oncology (Inst), Bristol Myers Squibb (Inst), Advanced Accelerator Applications (Inst), Agensys (Inst), BioXcel Therapeutics (Inst), Eisai (Inst), Mirati Therapeutics (Inst), Replimune (Inst), Medivation (Inst), Gilead Sciences (Inst)Expert Testimony: Celgene, Sanofi Jeffrey HolzbeierleinConsulting or Advisory Role: Basilea, KDx DiagnosticsResearch Funding: MDxHealth (Inst)Uncompensated Relationships: Astellas Medivation Arnauld VillersResearch Funding: Astellas Pharma (Inst), Janssen Oncology (Inst), Ipsen (Inst) Antonio AlcarazConsulting or Advisory Role: AstellasTravel, Accommodations, Expenses: Olympus, Ipsen, Janssen, Bayer Boris AlexeevHonoraria: AstraZeneca, Astellas Pharma, Ferring, Eisai, Janssen, Bayer, MSD, Merck, Pfizer, Roche, Sanofi, Bristol Myers SquibbConsulting or Advisory Role: AstraZeneca, Astellas Pharma, Bayer, Bristol Myers Squibb, Ferring, Janssen, Merck, Sanofi, Pfizer, MSD, Roche, EisaiSpeakers' Bureau: Janssen, Sanofi, Ferring, Astellas Pharma, Pfizer, AstraZeneca, Bayer, Merck, Bristol Myers Squibb, MSD, Eisai, RocheResearch Funding: AstraZeneca, Merck, Sanofi, Bayer, Astellas Pharma, Janssen, Bristol Myers Squibb, Bavarian Nordic, Pfizer, ICON Clinical Research, Eisai, MSD, RocheTravel, Accommodations, Expenses: AstraZeneca, Astellas Pharma, Bayer, Bristol Myers Squibb, Janssen, MSD, Pfizer, Sanofi Neal D. ShoreConsulting or Advisory Role: Bayer, Janssen Scientific Affairs, Dendreon, Tolmar, Ferring, Medivation/Astellas, Amgen, Pfizer, AstraZeneca, Myovant Sciences, Astellas Pharma, AbbVie, Merck, Bristol Myers Squibb/Sanofi, Boston Scientific, Clovis Oncology, Exact Imaging, FerGene, Foundation Medicine, CG Oncology, Invitae, MDxHealth, Myriad Genetics, Nymox, Propella Therapeutics, Genzyme, Sanofi, Sesen Bio, CG Oncology, Exact Sciences, Genesis Cancer Care, Pacific Edge Biotechnology, Phosphorus, UroGen Pharma, Speciality Networks, PreViewSpeakers' Bureau: Janssen, Bayer, Dendreon, Astellas Pharma, AstraZeneca, Clovis Oncology, Pfizer, Guardant Health, Merck, Foundation MedicineResearch Funding: AbbVie, Amgen, Astellas Pharma, AstraZeneca, Bayer, Bristol Myers Squibb/Pfizer, Boston Scientific, Clovis Oncology, Dendreon, Exact Imaging, Ferring, Foundation Medicine, Invitae, Janssen, MDxHealth, Merck, Myovant Sciences, Myriad Genetics, Nymox, Pfizer, Sanofi, Sesen Bio, Tolmar Francisco Gomez-VeigaHonoraria: AbbVie, Astellas, AstraZeneca, Bayer, Ferring, GE, GlaxoSmithKline, Ipsen, Janssen, SanofiConsulting or Advisory Role: AbbVie, Astellas, AstraZeneca, Bayer, Ferring, GE, GlaxoSmithKline, Ipsen, Janssen, SanofiSpeakers' Bureau: AbbVie, Astellas, AstraZeneca, Bayer, GE, Janssen, OrionResearch Funding: AbbVie, Astellas, AstraZeneca, Ipsen, JanssenTravel, Accommodations, Expenses: AbbVie, Astellas, Bayer, Janssen, Orion Brad RosbrookEmployment: PfizerStock and Other Ownership Interests: Pfizer Fabian ZohrenEmployment: PfizerStock and Other Ownership Interests: Pfizer, AlloVir Inc (I)Patents, Royalties, Other Intellectual Property: AlloVir Inc (I) Shunsuke YamadaEmployment: Astellas PharmaStock and Other Ownership Interests: Astellas Pharma Gabriel P. HaasEmployment: Astellas Pharma Arnulf StenzlConsulting or Advisory Role: Ipsen, Roche, Janssen, Alere, Bristol Myers Squibb, Steba Biotech, Synergo, Ferring, Bayer, Astellas PharmaResearch Funding: Karl Storz (Inst), Astellas Pharma, AstraZeneca, Medivation, Janssen, Johnson & Johnson (Inst), Roche (Inst), Cepheid (Inst), Immatics (Inst), Bayer (Inst), Novartis (Inst), Amgen (Inst), GenomeDx (Inst)Patents, Royalties, Other Intellectual Property: Patent A290/99 Implantable incontinence device, AT00/0001:C-Trap, implantable device to treat urinary incontinence, 2018/6579 Gene expression signature for subtype and prognostic prediction of renal cell carcinomaExpert Testimony: GBA PharmaTravel, Accommodations, Expenses: Janssen, Ipsen, Sanofi/Aventis, CureVac, Ferring, Astellas Pharma, Amgen, AstraZenecaNo other potential conflicts of interest were reported.

Figures

FIG 1.
FIG 1.
Efficacy analyses (intent-to-treat population) showing (A) Kaplan-Meier estimate of final OS analysis, (B) forest plot of OS subgroup analyses, (C) Kaplan-Meier estimates of time to first subsequent antineoplastic therapy, and (D) Kaplan-Meier estimates of rPFS (investigator assessed). ADT, androgen deprivation therapy; E, events; ECOG, Eastern Cooperative Oncology Group; ENZA, enzalutamide; HR, hazard ratio; NE, not evaluable; NR, not reached; OS, overall survival; PBO, placebo; PSA, prostate-specific antigen; RoW, rest of world; rPFS, radiographic progression-free survival.
See this image and copyright information in PMC

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