Abstract 635P
Background
The clinical benefit of ENZA + ADT versus PBO + ADT in reducing the risk of radiographic progression-free survival (rPFS) events has been shown in men with mHSPC, regardless of baseline PSA levels (> or ≤ median value) [ARCHES; NCT02677896]. Here, the aim was to further analyze efficacy outcomes by various baseline PSA categories.
Methods
Patients with mHSPC were randomized 1:1 to ENZA (160 mg/day) + ADT or PBO + ADT. Prior ADT and up to six cycles of prior docetaxel were permitted before baseline assessment of PSA levels and study treatment initiation. Post hoc analyses of the primary endpoint (rPFS) and other secondary endpoints by different baseline PSA categories at time of randomization were conducted to assess the efficacy of ENZA + ADT.
Results
In the overall population (N=1150), >90% received prior ADT and 18% had prior docetaxel treatment. Median duration (range) of prior ADT was 1.6 months (0.03–55.3) for ENZA + ADT patients versus 1.6 months (0.03–198.8) for PBO + ADT patients. Of the overall population with available baseline PSA values (n=1146), 135 patients had ≤0.2 μg/L, 388 patients had >0.2−4 μg/L, and 623 patients had >4 μg/L PSA at baseline (Table). Across these subgroups, the beneficial effect of ENZA + ADT on rPFS was observed, irrespective of baseline PSA (Table); similar results were also observed with other endpoints such as time to PSA progression and time to castration resistance. Table: 635P
| PSA baseline categories | |||
| Endpoint, HR (95% CI) a | ≤0.2 μg/L (n=63; b n=72 c ) | >0.2−4 μg/L (n=194; b n=194 c ) | >4 μg/L (n=315; b n=308 c ) |
| rPFSd | 0.60 (0.27, 1.32) | 0.32 (0.20, 0.51) | 0.41 (0.30, 0.57) |
| Time to PSA progressione | 0.21 (0.05, 1.00) | 0.12 (0.06, 0.25) | 0.21 (0.14, 0.30) |
| Time to castration resistance | 0.43 (0.20, 0.96) | 0.26 (0.17, 0.41) | 0.27 (0.20, 0.37) |
aHR <1 favors ENZA + ADT; HR >1 favors PBO + ADT;bENZA + ADT;cPBO + ADT;dAssessed by independent central review or death within 24 weeks of treatment discontinuation;ePSA progression was defined as a ≥25% increase and an absolute increase of ≥2 ng/mL above the nadir, confirmed by a second consecutive value ≥3 weeks later CI, confidence interval; HR, hazard ratio
Conclusions
These post hoc analyses demonstrate the clinical benefit of ENZA + ADT versus PBO + ADT based on rPFS and secondary clinical endpoints in patients with mHSPC, irrespective of patients’ baseline PSA values.
Clinical trial identification
ARCHES; NCT02677896.
Editorial acknowledgement
Medical writing and editorial assistance were provided by Beatrice Vetter-Ceriotti, PhD, and Lauren Smith from Complete HealthVizion, funded by the study sponsors.
Legal entity responsible for the study
Astellas Pharma Inc. and Pfizer Inc.
Funding
This study was funded by Astellas Pharma Inc. and Pfizer Inc., the co-developers of enzalutamide.
Disclosure
A. Alcaraz: Travel/Accommodation/Expenses: Astellas Pharma; Travel/Accommodation/Expenses: Olympus; Travel/Accommodation/Expenses: Ipsen; Travel/Accommodation/Expenses: Bayer; Travel/Accommodation/Expenses: Janssen. R.Z. Szmulewitz: Advisory/Consultancy: AstraZeneca; Advisory/Consultancy, Research grant/Funding (self): Abbvie; Advisory/Consultancy: Exelixis; Advisory/Consultancy: Merck; Advisory/Consultancy: Amgen; Advisory/Consultancy, Research grant/Funding (self): Janssen Oncology; Advisory/Consultancy: Sanofi; Honoraria (self), Advisory/Consultancy, Research grant/Funding (self): Astellas Pharma Inc. ; Advisory/Consultancy: Pfizer; Travel/Accommodation/Expenses: Corcept Therapeutics; Licensing/Royalties, Patent licensed by University of Chicago of which I am co-inventor to Corcept Therapeutics for combination AR/GR inhibition in prostate cancer: University of Chicago; Research grant/Funding (self): Incyte; Research grant/Funding (self): Macrogenics. N. Shore: Advisory/Consultancy, Speaker Bureau/Expert testimony: Bayer; Advisory/Consultancy: Janssen Scientific Affairs; Advisory/Consultancy, Speaker Bureau/Expert testimony: Dendreon; Advisory/Consultancy: Tolmar; Advisory/Consultancy: Ferring; Advisory/Consultancy: Medivation / Astellas; Advisory/Consultancy: Amgen; Advisory/Consultancy: Pfizer; Advisory/Consultancy: AstraZeneca; Advisory/Consultancy: Genentech / Roche; Advisory/Consultancy: Myovant Sciences; Advisory/Consultancy: Astellas Pharma Inc; Advisory/Consultancy: Merck; Speaker Bureau/Expert testimony: Janssen. E.D. Crawford: Speaker Bureau/Expert testimony: Ferring; Speaker Bureau/Expert testimony: Bayer; Non-remunerated activity/ies, Astellas provided medical writing for this abstract: Astellas Pharma Inc. . D.P. Petrylak: Advisory/Consultancy, Research grant/Funding (institution): Bayer; Advisory/Consultancy: Exelixis; Advisory/Consultancy, Research grant/Funding (institution): Pfizer; Advisory/Consultancy, Research grant/Funding (institution): Roche; Advisory/Consultancy: Astellas Pharma Inc.; Advisory/Consultancy, Research grant/Funding (institution): AstraZeneca; Advisory/Consultancy, Research grant/Funding (institution): Lilly; Advisory/Consultancy: Amgen; Advisory/Consultancy: Boehringer Ingelheim; Advisory/Consultancy, Research grant/Funding (institution): Bristol-Myers Squibb; Advisory/Consultancy, Research grant/Funding (institution): Clovis Oncology; Advisory/Consultancy: Incyte; Advisory/Consultancy: Janssen; Advisory/Consultancy: Pharmacyclics; Advisory/Consultancy, Research grant/Funding (institution): Seattle Genetics; Advisory/Consultancy: Urogen Pharma; Advisory/Consultancy, Research grant/Funding (institution): Advanced Accelerator Applications; Advisory/Consultancy: Ipsen; Speaker Bureau/Expert testimony: Celgene; Speaker Bureau/Expert testimony, Research grant/Funding (institution): Sanofi; Shareholder/Stockholder/Stock options: Bellicum Pharmaceuticals; Shareholder/Stockholder/Stock options: Tyme; Research grant/Funding (institution): Progenics; Research grant/Funding (institution): Endocyte; Research grant/Funding (institution): Genentech; Research grant/Funding (institution): Merck; Research grant/Funding (institution): Astellas Medivation; Research grant/Funding (institution): Novartis; Research grant/Funding (institution): Innocrin Pharma; Research grant/Funding (institution): MedImmune. J. Holzbeierlein: Research grant/Funding (institution): Astellas Pharma Inc. ; Research grant/Funding (institution): MDxHealth. A. Villers: Advisory/Consultancy, Research grant/Funding (institution), Travel/Accommodation/Expenses: Astellas Pharma Inc. ; Travel/Accommodation/Expenses: Janssen-Cilag; Research grant/Funding (institution): IPSEN. A.A. Azad: Honoraria (self), Advisory/Consultancy: Janssen; Honoraria (self), Advisory/Consultancy, Speaker Bureau/Expert testimony, Research grant/Funding (self), Travel/Accommodation/Expenses: Astellas Pharma Inc. ; Honoraria (self), Advisory/Consultancy, Speaker Bureau/Expert testimony, Research grant/Funding (institution): Novartis; Honoraria (self), Advisory/Consultancy: Tolmar; Honoraria (self), Speaker Bureau/Expert testimony: Bayer; Honoraria (self), Advisory/Consultancy: Telix Pharmaceuticals; Honoraria (self), Speaker Bureau/Expert testimony: Amgen; Advisory/Consultancy, Research grant/Funding (institution), Travel/Accommodation/Expenses: Sanofi; Advisory/Consultancy, Research grant/Funding (institution): AstraZeneca; Advisory/Consultancy, Research grant/Funding (institution): Pfizer; Advisory/Consultancy, Research grant/Funding (institution): Bristol-Myers Squibb; Research grant/Funding (institution), Travel/Accommodation/Expenses: Merck Serono; Research grant/Funding (institution): GlaxoSmithKline; Research grant/Funding (institution): Aptevo Therapeutics; Research grant/Funding (institution): MedImmune; Research grant/Funding (institution): Bionomics; Research grant/Funding (institution): Synthorx. B. Alekseev: Advisory/Consultancy, Speaker Bureau/Expert testimony, Research grant/Funding (self), Travel/Accommodation/Expenses: AstraZeneca; Advisory/Consultancy, Speaker Bureau/Expert testimony, Research grant/Funding (self), Travel/Accommodation/Expenses: Astellas Pharma Inc. ; Advisory/Consultancy, Speaker Bureau/Expert testimony, Research grant/Funding (self), Travel/Accommodation/Expenses: Bayer; Advisory/Consultancy, Speaker Bureau/Expert testimony, Research grant/Funding (self), Travel/Accommodation/Expenses: Bristol-Myers Squibb; Advisory/Consultancy, Speaker Bureau/Expert testimony: Ferring; Advisory/Consultancy, Speaker Bureau/Expert testimony, Research grant/Funding (self), Travel/Accommodation/Expenses: Janssen; Advisory/Consultancy, Speaker Bureau/Expert testimony, Research grant/Funding (self): Merck; Advisory/Consultancy, Speaker Bureau/Expert testimony, Research grant/Funding (self), Travel/Accommodation/Expenses: Sanofi; Advisory/Consultancy, Speaker Bureau/Expert testimony, Research grant/Funding (self), Travel/Accommodation/Expenses: Pfizer; Travel/Accommodation/Expenses: MSD; Research grant/Funding (self): Bavarian Nordic; Research grant/Funding (self): ICON Clinical Research. T. Iguchi: Advisory/Consultancy, Speaker Bureau/Expert testimony, Research grant/Funding (self): Astellas Pharma Inc. ; Advisory/Consultancy, Speaker Bureau/Expert testimony, Research grant/Funding (self): Bayer Yakuhin; Advisory/Consultancy, Speaker Bureau/Expert testimony: Janssen; Speaker Bureau/Expert testimony: Sanofi. F. Gomez-Veiga: Non-remunerated activity/ies, Astellas Pharma Inc. provided medical writing for preparation of this abstract: Astellas Pharma Inc. B. Rosbrook: Shareholder/Stockholder/Stock options, Full/Part-time employment: Pfizer. J. Sugg: Full/Part-time employment: Astellas Pharma Inc.; Shareholder/Stockholder/Stock options: AstraZeneca. G.P. Haas: Full/Part-time employment: Astellas Pharma Inc. A. Stenzl: Advisory/Consultancy, Travel/Accommodation/Expenses: Ipsen; Advisory/Consultancy: Roche; Advisory/Consultancy, Research grant/Funding (self), Travel/Accommodation/Expenses: Janssen; Advisory/Consultancy: Alere; Advisory/Consultancy: Bristol-Myers Squibb; Advisory/Consultancy: Steba Biotech; Travel/Accommodation/Expenses: Sanofi/Aventis; Travel/Accommodation/Expenses: CureVac; Travel/Accommodation/Expenses: Ferring; Speaker Bureau/Expert testimony: GBA; Licensing/Royalties: Patent A290/99 Implantable incontinence device; Licensing/Royalties: AT00/0001:C-Trap, implantable device to treat urinary incontinence; Licensing/Royalties: 2018/6579 Gene-expression signature for subtype and prognostic prediction of renal cell carcinoma; Research grant/Funding (self): Karl Storz; Research grant/Funding (self): Astellas Pharma Inc. ; Research grant/Funding (self): AstraZeneca; Research grant/Funding (self): Medivation. A.J. Armstrong: Advisory/Consultancy, Speaker Bureau/Expert testimony, Research grant/Funding (institution), Travel/Accommodation/Expenses: Bayer; Advisory/Consultancy, Research grant/Funding (institution): Sanofi; Honoraria (self), Advisory/Consultancy, Speaker Bureau/Expert testimony, Research grant/Funding (institution), Travel/Accommodation/Expenses: Dendreon; Advisory/Consultancy, Research grant/Funding (institution): Medivation; Advisory/Consultancy, Travel/Accommodation/Expenses: Janssen Biotech; Advisory/Consultancy, Research grant/Funding (institution): Pfizer; Advisory/Consultancy, Travel/Accommodation/Expenses: Astellas Scientific and Medical Affair; Advisory/Consultancy: Clovis Oncology; Advisory/Consultancy: AstraZeneca; Licensing/Royalties, Received by institution: Circulating tumor cell novel capture technology; Honoraria (self), Research grant/Funding (institution): Janssen Oncology; Research grant/Funding (institution): Novartis; Research grant/Funding (institution): Astellas Pharma Inc. ; Research grant/Funding (institution): Gilead Sciences; Research grant/Funding (institution): Roche/Genentech; Research grant/Funding (institution): Active Biotech; Research grant/Funding (institution): Bristol-Myers Squibb; Research grant/Funding (institution): Constellation Pharmaceuticals; Research grant/Funding (institution): Merck.