Page 9 - CUA2019 Abstracts - Oncology-Prostate

2019 CUA Abstr
2019 CUA AbstrACtsACts

Podium Session 3: Prostate Cancer

June 30, 2019; 1150–1250

POD-3.1 POD-3.2
Phase 3 study of androgen-deprivation therapy (ADT) with A novel predictor of clinical progression in patients on active
enzalutamide (ENZA) or placebo (PBO) in metastatic hormone- surveillance for prostate cancer
sensitive prostate cancer (mHSPC): The ARCHES trial Guan Hee Tan , Antonio Finelli , Ardalan Ahmad , Marian Wettstein ,
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Cristiano Ferrario , Andrew J. Armstrong , Russell Szmulewitz , Daniel Alexandre Zlotta , Neil E. Fleshner , Robert Hamilton , Girish S. Kulkarni ,
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Petrylak , Arnauld Villers , Arun Azad , Antonio Alcaraz , Boris Alekseev , Gregory Nason , Khaled Ajib , Nathan Perlis 1
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Taro Iguchi , Neal D. Shore , Brad Rosbrook , Jennifer Sugg , Benoit 1 Division of Urology, University Health Network, Toronto, ON, Canada
Baron , Lucy Chen , Arnulf Stenzl 14 Introduction: To minimize morbidity of surgery or radiation, active surveil-
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1 Jewish General Hospital and McGill University, Montréal, QC, Canada; lance (AS) is standard of care in low-risk prostate cancer (PCa). Predicting
2 Duke Cancer Institute Center for Prostate and Urologic Cancers, Durham, which men on AS will progress and require active treatment is challenging.
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NC, United States; The University of Chicago, Chicago, IL, United States; This study describes a novel total cancer location (TCLo) density index and
4 Yale Cancer Center, New Haven, CT, United States; University Hospital aims to determine its performance in predicting clinical progression (CP)
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Centre, Lille University, Lille, France; Monash Health, Melbourne, Australia; and grade progression (GP).
7 Hospital Clinic de Barcelona, Barcelona, Spain; Hertzen Moscow Cancer Methods: This was a retrospective study of patients on AS after confirma-
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Research Institute, Moscow, Russian Federation; Osaka City University tory biopsy (CBx). We excluded patients with Gleason ≥7 at CBx, less
Graduate School of Medicine, Osaka, Japan; Carolina Urologic Research than two years’ followup, and incomplete data. TCLo was the number of
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Center, Myrtle Beach, SC, United States; Pfizer Inc., San Diego, CA, United locations with positive cores at diagnosis (DBx) and CBx. TCLo density was
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States; Astellas Pharma Inc., Northbrook, IL, United States; Astellas TCLo/prostate volume (PV). CP was progression to any active treatment
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Pharma Inc., Leiden, Netherlands; University Hospital, Eberhard Karls while GP occurred if Gleason ≥7 was identified on repeat biopsy or surgical
University, Tübingen, Germany pathology. Independent predictors of time to CP or GP were estimated with
Introduction: Enzalutamide (ENZA), a potent androgen receptor inhibi- Cox regression. Kaplan-Meier analysis compared progression-free survival
tor, has demonstrated benefit in men with metastatic and non-metastatic curves between TCLo density groups. Test characteristics of TCLo were
castration-resistant prostate cancer (CRPC). Efficacy of ENZA with andro- explored with receiver operating characteristic (ROC) curves
gen-deprivation therapy (ADT) in men with metastatic hormone-sensitive Results: Between 2012 and 2015, 421 patients had a CBx. We included 181
prostate cancer (mHSPC) is unknown. patients who met inclusion criteria. The mean age of patients at the start of
Methods: ARCHES is a multinational, double-blind, phase 3 study AS was 62.6 years (standard deviation [SD] 7.13) and the median prostate-
(NCT02677896). Patients with mHSPC were randomized 1:1 to ENZA specific antigen (PSA) at diagnosis was 5.16 ng/mL (interquartile range
(160 mg/day) + ADT or placebo (PBO) + ADT, stratified by disease vol- [IQR] 3.44). Mean PV was 45.0 mL (SD 18.1). The median TCLo density
ume (CHAARTED criteria) and prior docetaxel therapy. Primary endpoint was 0.049 (IQR 0.06). A high TCLo density score (>0.05) was independently
was radiographic progression-free survival (rPFS) assessed centrally or associated with time to CP, with hazard ratio (HR) 4.7 (95% confidence
death within 24 weeks of treatment discontinuation. Secondary endpoints interval [CI] 2.62–8.42; p<0.001) and GP, with HR 4.25 (95% CI 2.06–8.74;
included time to prostate-specific antigen (PSA) progression, PSA and radio- p<0.001) (Fig. 1). TCLo density performed better than percentage positive
graphic responses, and overall survival (OS). Treatment continued until cores at CBx in predicting CP (Fig. 2).
disease progression or unacceptable toxicity. Conclusions: TCLo density has the potential to stratify patients into low-
Results: A total of 1150 men were randomized to ENZA (n=574) or PBO or high-risk for CP and GP while on AS for low-risk PCa. This should be
(n=576); baseline characteristics were balanced between groups. Overall, validated with a larger, prospective sample population.
67% had distant metastasis at initial diagnosis; 63% had high-volume dis- This paper has figures, which may be viewed online at:
ease, 18% had prior docetaxel. Median followup was 14.4 months. ENZA https://2019.cua.events/webapp/lecture/32
+ ADT significantly improved rPFS (Table 1); similar significant improve-
ments in rPFS were reported in prespecified subgroups of disease vol- POD-3.3
ume, pattern of spread, region, and prior docetaxel (hazard ratios [HRs] Comparison of bone scintigraphy and 18F-fluorocholine positron
0.24–0.53). Secondary endpoints improved with ENZA + ADT (Table 1); emission tomography-computed tomography (18F-FCH PET/CT)
OS data are immature. Grade 3–4 adverse events (AEs) were reported in to stage high-grade prostate cancers shows 18FDG-PET/CT has a
23.6% of ENZA patients vs. 24.7% of PBO patients with no unexpected AEs. better accuracy to detect bone metastasis
Conclusions: ENZA + ADT significantly improved rPFS and other efficacy 1 1 1 1
endpoints vs. PBO + ADT in men with mHSPC, with a preliminary safety Samuel Otis-Chapados , Louis Lacombe , Yves Fradet , Vincent Fradet , Paul
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analysis that appears consistent with the safety profile of ENZA in previous Toren , Thierry Dujardin , Michele Lodde , Rabi Tiguert , Frédéric Pouliot
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CRPC clinical trials. Department of Surgery, Urology Division, CHU de Québec, Université
This paper has a figure, which may be viewed online at: Laval, Québec City, QC, Canada
https://2019.cua.events/webapp/lecture/275 Introduction: The accuracy of computed tomography (CT)-coupled
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This study was funded by Astellas Pharma Inc. and Medivation LLC, a Pfizer F-fluorodeoxyglucose positron emission tomography (FDG-PET/CT) for
Company, the co-developers of enzalutamide. Medical writing and editing prostate cancer (PCa) staging has not been studied in depth. We have shown
assistance provided by Stephanie Rippon, MBio, and Lauren Smith from recently in a series of Gleason 8 PCa at biopsy, that high intraprostatic
Complete HealthVizion, funded by the study sponsors. FDG uptake (SUVmax) was predictive of adverse pathological prognostic
features after surgery, earlier biochemical recurrence, and earlier castration
resistance. High intraprostatic FDG uptake in the primary tumour, there-
fore, defines patients at very high risk of failure and death. In this study,
S120 CUAJ • June 2019 • Volume 13, Issue 6(Suppl5)
© 2019 Canadian Urological Association