Table: 809P Multivariable Cox-Regression OS Analysis
Variable HR (95%CI) p-value
Statin Use 0.79 (0.62-0.99) 0.048 Treatment Arm 0.66 (0.55-0.79) <0.001 Baseline PSA 1 (1-1) 0.394 Baseline Hb 0.89 (0.85-0.93) <0.001 Baseline ALP 1 (1-1) 0.009 Visceral Metastases 1.36 (1.11-1.68) 0.003 ECOG PS 1.67 (1.43-1.96) <0.001
Conclusions: Use of statins by pts treated in the TROPIC trial was associated with a longer OS, independent of treatment arm and other prognostic variables. Further anal-yses will elucidate the role of statins in mCRPC.
Clinical trial identification: EudraCT: 2006-003087-59; NCT00417079. Legal entity responsible for the study: David Lorente / Prostate Targeted Therapy Group.
Funding: The TROPIC trial was funded by Sanofi Aventis. No specific funding was received for the development of the current abstract.
Disclosure: All authors have declared no conflicts of interest.
810P Abiraterone acetate plus prednisone and LHRH therapy versus abiraterone acetate plus prednisone while sparing LHRH therapy in patients with progressive, metastatic and chemotherapy-naı¨ve, castration-resistant prostate cancer: Results from the SPARE-trial (NCT02077634) C. Ohlmann1 , Z. Roger2 , C. Ru¨ssel3 , E. Hellmis4 , H. Suttmann5 , M. Janssen6 , A. Hu¨bner7 , J. Dahm8 , J. Gleißner9 , M. Scheffler10 , S. Feyerabend11 , J. Telle12 , J. Klier13 1
Urology, Malteser Krankenhaus Bonn, Bonn, Germany,2
Urology, Praxis fu¨r Urologie Pankow, Berlin, Germany,3
Urology, Praxisgemeinschaft fu¨r Urologie, Borken, Germany, 4
Urology, Urologikum Duisburg, Duisburg, Germany,5
Urology, Urologikum Hamburg, Hamburg, Germany,6
Urology, Saarland University Medical Center, Hamburg, Germany, 7
Urology, WK Nord GmbH & Co. KG, Rostock, Germany,8
Urology, PandaMED - €UBAG, Wuppertal, Germany,9
Urology, DGU Wuppertal, Wuppertal, Germany,10 Urology, Gemeinschaftspraxis fu¨r Urologie, Zwickau, Germany,11
Urologic Oncology, Studienpraxis Urologie, Nu¨rtingen, Germany,12
Urology, Urologische Praxis Wu¨rzburg, Wu¨rzburg, Germany,13
Urology, Praxis, Cologne, Germany
Background: The value of continuation of luteinizing hormone-releasing hormone (LHRH) therapy in castration-resistant prostate cancer (CRPC) remains controversial and clear evidence is lacking. Especially upon treatment with the life-prolonging cyto-chrome P450 17-alpha-hydroxylase/C17,20lyase (Cyp17)-inhibitor, abiraterone, which in combination with prednisone, has the ability to further suppress testosterone serum levels over LHRH therapy alone, continuation of LHRH therapy seems to be negligible. The aim of the SPARE trial therefore was to explore the role of continuation of LHRH therapy when starting treatment with abiraterone acetate plus prednisone (AAþP) in patients with asymptomatic or mildly symptomatic, chemotherapy-naı¨ve CPRC. Methods: Patients were randomized to receive continuing LHRH therapy versus LHRH withdrawal at the time of starting abiraterone AAþP therapy (NCT02077634). The primary endpoint was rate of rPFS at month 12. Secondary endpoints included PSA response rate, objective response, time to PSA progression and safety. Results: Altogether, 68 patients were randomized. Median age was 75 (60-86) years with a median PSA at baseline of 23.9 (0.17-1680) ng/ml. Results of the secondary end-points were evaluated.
Table: 810P
LHRHþAAþP AAþP HR (p-value)
Patients (n) 34 33
Median age (range) 74 (60-86) years 76 (60-86) years Median baseline PSA
(range) 31.9 (0.17-313.2) ng/ml 20.59 (1.97-1680) ng/ml PSA-decline50% 23/34 (67.6%) 24/33 (72.7%) Median treatment duration (d) 266 420 1.667 (0.197)* Time to PSA progression (d) 288 336 1.733 (0.188)*
*study was not powered for these endpoints.
Conclusions: The results of the exploratory study show that AAþ P without continua-tion of LHRH therapy leads to considerable PSA response rates and longer time to PSA progression. The currently assessed efficacy is comparable to the results of the COU-AA-302 trial, hypothesising that continuation of LHRH therapy may not be necessary upon treatment with AAþ P. Results on the primary endpoint and the safety profile are pending and are currently being evaluated.
Clinical trial identification: NCT02077634.
Legal entity responsible for the study: Saarland University. Funding: Janssen-Cilag.
Disclosure: C. Ohlmann: Research funding: Janssen-Cilag. All other authors have declared no conflicts of interest.
811P Association of grade3 neutropenia (NP) with outcomes in patients with metastatic castration-resistant prostate cancer (mCRPC) receiving cabazitaxel A. Meisel1 , R. de Wit2 , S. Oudard3 , O. Sartor4 , F. Stenner-Liewen5 , Z. Shun6 , A. Ozatilgan7 , M. Eisenberger8 , J.S. de Bono9 1
Internal Medicine - Hematology and Oncology, Stadtspital Ward; Department of Nuclear Zurich, University Hospital of Zurich; Institute of Pharmaceutical Sciences, Federal Institute of Technology, Zurich, Switzerland,2
Medical Oncology, Erasmus University Medical Center, Rotterdam, Netherlands,3
Service d’Oncologie Me´dicale, Georges Pompidou European Hospital, Rene Descartes University, Paris, France, 4
Medicine and Urology, Tulane Cancer Center, New Orleans, LA, USA,5
Department of Oncology, University Hospital of Basel, Basel, Switzerland,6
Biostatistics, Sanofi, Bridgewater, NJ, USA,7
Global Medical Oncology, Sanofi, Cambridge, MA, USA,8 The Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins Hospital, Baltimore, MD, USA,9
Division of Clinical Studies, Drug Development Unit, Royal Marsden NHS Foundation Trust/The Institute of Cancer Research, Sutton, UK
Background:Subset analysis of trials investigating taxanes in patients with mCRPC suggest an association between Grade3 NP and disease outcomes. In the Phase 3 PROSELICA trial (NCT01308580), NP was more common in patients receiving cabazi-taxel 25 mg/m2(C25) vs cabazitaxel 20 mg/m2(C20) - 73% vs 42%, respectively. Post hoc analyses of PROSELICA examined the relationship between incidence of NP, sur-vival and response.
Methods:PROSELICA assessed the non-inferiority of C20 (n¼ 598) vs C25 (n ¼ 602) in terms of overall survival (OS) in men with mCRPC. Prophylactic granulocyte col-ony-stimulating factor was given to patients with Grade3 NP. OS and progression-free survival (PFS) were analyzed using Kaplan-Meier (KM) estimates and Cox propor-tional hazard models. Nominal p values were determined by log-rank tests. Prostate-specific antigen response rate (PSArr; defined as proportion of patients with a > 50 % PSA decline from baseline) was analyzed in the eligible population using KM estimates with Chi2tests and odds ratios. OS, PFS and PSArr were correlated with Grade3 NP occurrence and baseline neutrophilia (neutrophils7000 G/l) by univariate analysis. Results:In the intent-to-treat (ITT) population, development of Grade3 NP was associated with better PSArr, PFS and OS (p < 0.001; Table). The positive association was observed in both treatment arms and in poor-risk patients with baseline neutrophilia.
Table: 811P
Population Outcome Grade
3 NP No Grade 3 NP Hazard ratio/Odds ratio p value ITT population (n¼ 1200)
OS, months (mo) 15.1 12.4 0.78 0.0002
PFS, mo 3.7 2.8 0.79 0.0001 PSArr, % n¼ 1079 44.1 25.5 2.3 <0.0001 C25 (n¼ 602) OS, mo 15.3 12.2 0.77 0.009 PFS, mo 3.5 3.5 0.84 0.07 PSArr, % n¼ 538 46.2 34.5 1.6 0.015 C20 (n¼ 598) OS, mo 14.6 12.6 0.78 0.006 PFS, mo 4.2 2.3 0.75 0.0008 PSArr, % n¼ 541 40.7 21.3 2.5 <0.0001 Neutrophilia (n¼ 174) OS, mo 12.8 7.5 0.63 0.004 PFS, mo 4.1 2.1 0.66 0.008 PSArr, % n¼ 156 43.8 16.9 3.8 0.0002
Conclusions:Post hoc assessment of Grade3 NP in PROSELICA was associated with improved survival and response to cabazitaxel independent of dose. These results are consistent with data obtained in the Phase 3 TAX327 (docetaxel) and TROPIC (cabazi-taxel) trials. Funded by Sanofi.
Clinical trial identification:NCT01308580.
abstracts
Annals of Oncology
viii280 | Genitourinary tumours, prostate
Volume 29 | Supplement 8 | October 2018
Editorial acknowledgement:Editorial assistance was provided by Danielle Lindley of Meditech Media Ltd, funded by Sanofi.
Legal entity responsible for the study:Sanofi. Funding:Sanofi.
Disclosure:Meisel: Advisor: Astellas, Roche, Celgene, Novartis, Vifor, Sanofi, Amgen, Merck; Expert testimony: Sanofi; Research funding: Bayer (himself), Merck (institu-tion); Expenses: Amgen, Astellas, Sanofi, Servier, Roche, Boehringer Ingelheim; Intellectual property: Merck. R. de Wit: Consultancy, Speaker fees: Sanofi. S. Oudard: Consultancy, Advisory role, Honoraria, Expense: Sanofi, Astellas, Janssen, and Ipson; Research funding: Sanofi; Speakers bureau: Sanofi, Janssen. O. Sartor: Advisor: Bellicum Pharmaceuticals, Dendreon; Advisor, Expenses: Bayer, Johnson & Johnson, Medivation, Oncogenex, Sanofi, Tokai Pharmaceuticals, AstraZeneca, Progenics; Funding (Institute): Bayer, Johnson & Johnson, Sanofi, Dendreon, Endocyte, Innocrin Pharma, Progenics. F. Stenner-Liewen: Consultancy, Advisory role, Research, expenses: Sanofi. S. Guillonneau, A. Ozatilgan: Employee: Sanofi. M. Eisenberger: Honoraria, Consultancy, Advisory role: Sanofi, Pfizer, Astellas; Research: Sanofi; Expenses: Sanofi, Pfizer. J.S. de Bono: Honoraria: Sanofi; Advisor: Sanofi, AstraZeneca, GSK, Genentech, Roche, Merck; Speakers bureau: AstraZeneca/MedImmune; Research funding (Institute): AstraZeneca/MedImmune, GSK, Sanofi, Merck Sharp & Dohme, Genmab, Genentech; Patent on abiraterone acetate with prednisone.
812P Post hoc responder analysis of health-related quality of life (HRQL) in patients with metastatic castration-resistant prostate cancer (mCRPC) receiving cabazitaxel in the phase III PROSELICA and FIRSTANA trials A. Thiery Vuillemin1 , K. Fizazi2 , O. Sartor3 , S. Oudard4 , D. Bury5 , S. Guillonneau6 , A. Ozatilgan7 , M. Eisenberger8 , J.S. de Bono9 1
Medical Oncology, Centre Hospitalier Re´gional Universitaire, Besancon, France, 2
Cancer Medicine, Institut Gustave Roussy, Villejuif, France,3
Medicine and Urology, Tulane Cancer Centre, New Orleans, LA, USA,4
George Pompidou European Hospital, Rene´ Descartes University, Paris, France,5
Real World Evidence/Global Clinical Outcomes, Sanofi US, Cambridge, MA, USA,6
Biostatistics, Sanofi, Chilly-Mazarin, France,7
Global Medical Oncology, Sanofi US, Cambridge, MA, USA,8 The Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins Hospital, Baltimore, MD, USA, 9
Division of Clinical Studies Drug Development Unit, Royal Marsden NHS Foundation Trust/The Institute of Cancer Research, Sutton, UK
Background: PROSELICA (NCT01308580) assessed the non-inferiority of cabazitaxel 20 mg/m2(C20) vs 25 mg/m2(C25) in patients (pts) with mCRPC post docetaxel, while FIRSTANA (NCT01308567) investigated whether C20 and C25 were superior to doce-taxel 75 mg/m2(D75) in chemotherapy-naive mCRPC. This analysis evaluated the impact of cabazitaxel on HRQL in both trials.
Methods: Alongside pain and analgesic score, HRQL was assessed using the Functional Assessment of Cancer Therapy Prostate (FACT-P) questionnaire. The analysis focused on FACT-P (clinically meaningful improvement or deterioration of total score [TS]) among responders.
Results: Pt baseline characteristics are shown in the table. In PROSELICA, 57.2% and 59.4% of pts receiving C20 and C25 had FACT-P TS improvements; in FIRSTANA, 63.5%, 62.3% and 57.7% of pts receiving C20, C25 and D75 had FACT-P TS improve-ments. In FACT-P responders, FACT-P TS improvements occurred as early as Cycle (C) 1 (mean change from baseline: PROSELICA C20 10.4, n¼ 264; C25 10.6, n ¼ 266; FIRSTANA C20 11.7, n¼ 206; C25 11.7, n ¼ 202; D75 9.0, n ¼ 195); these were largely maintained. For pts with a pain response in PROSELICA, FACT-P TS improvements occurred as early as C1 (C20 6.8, n¼ 71; C25 11.1, n ¼ 81) and were maintained until C8 (C20 10.6, n¼ 43; C25 9.6, n ¼ 44). In FIRSTANA, FACT-P TS improvements in pts with a pain response were seen as early as C1 or C2 (C1: C20 15.5, n¼ 41; C25 12.5, n¼ 41; D75, 7.9, n ¼ 32) and maintained until C9 (C20 9.0, n ¼ 27; C25 10.5, n ¼ 26; D75 16.4, n¼ 20). In pts with a tumor or PSA response, HRQL was maintained for all treatment arms in both studies. Additional results for clinical responder subgroups and FACT-P subscales will be presented.
Conclusions: More than half of the pts experienced HRQL improvements, which were maintained. Pts with a pain response experienced HRQL improvements. Funding: Sanofi.
Clinical trial identification: PROSELICA: NCT01308580. FIRSTANA: NCT01308567. Editorial acknowledgement: Editorial assistance was provided by Mark Cockerill of MediTech Media Ltd, funded by Sanofi.
Legal entity responsible for the study: Sanofi. Funding: Sanofi.
Disclosure: A. Thiery Vuillemin: Employee: AstraZeneca; Consultancy, advisory role: Novartis, Sanofi, Astellas, Pfizer, Janssen, Ipsen, Pfizer; Research funding: Pfizer; Travel, accommodation and expenses: Novartis, Sanofi, Pfizer. K. Fizazi: Honoraria: Janssen, Sanofi, Astellas, Takeda; Consultancy, Advisory role: Janssen Oncology, Bayer, Astellas, Sanofi, Orion Pharma GmbH, Curevac, AstraZeneca, ESSA, Genentech; Travel, accommodation and expenses: Amgen. O. Sartor: Advisor: Bellicum Pharmaceuticals, Dendreon; Advisor and expenses: Bayer, Johnson & Johnson, Medivation, Oncogenex, Sanofi, Tokai Pharmaceuticals, AstraZeneca, Progenics; Institute: funding: Bayer, Johnson & Johnson, Sanofi, Dendreon, Endocyte, Innocrin Pharma, Progenics. S. Oudard: Consultancy, advisory role, honoraria, expenses: Sanofi, Astellas, Janssen, Ipson; Research funding: Sanofi; Speakers bureau: Sanofi, Janssen. D. Bury: Contractor: Sanofi; Employee: Artech. S. Guillonneau, A. Ozatilgan: Employee: Sanofi. M. Eisenberger: Honoraria, Consultancy, Advisory role: Sanofi, Pfizer, Astellas; Research: Sanofi; Expenses: Sanofi, Pfizer. J.S. de Bono: Honoraria: Sanofi; Advisor: Sanofi, AstraZeneca, GSK, Genentech, Roche, Merck; Speakers’ bureau: AstraZeneca/MedImmune; Research funding (institute): AstraZeneca/ MedImmune, GSK, Sanofi, Merck Sharp & Dohme, Genmab, Genentech; Patent on abiraterone acetate with prednisone.
813P Treatment of metastatic castration-resistant prostate cancer (mCRPC); Survival by type of progression at initiation of treatment
D.G. Robbrecht1 , R.J. van Soest2 , I.F. Tannock3 , S. Oudard4 , B. Tombal5 , M. Eisenberger6 , F. Mercier7 , R. de Wit1 1
Medical Oncology, Erasmus MC Daniel den Hoed Cancer Center, Rotterdam, Netherlands,2
Urology, Erasmus MC Daniel den Hoed Cancer Center, Rotterdam, Netherlands,3
Medical Oncology, Princess Margaret Hospital, Toronto, ON, Canada, 4
Immunothe´rapie et Traitement Antiangioge´nique en Pathologie Cance´rologique, Hopital European George Pompidou, Paris, France,5
Urology, Cliniques Universitaires St. Luc, Brussels, Belgium,6
Medical Oncology, Johns Hopkins Sidney Kimmel Cancer Center, Baltimore, MD, USA,7
Stat Process, Sanofi, Charlotte, Nc, France
Background: The usual sequence of progression events in mCRPC patients treated with new hormonal agents is known: PSA progression, followed by radiological pro-gression and finally pain propro-gression (Ryan, NEJM 2013; Beer, NEJM 2014). Although pain was associated with poor overall survival (OS) in the TAX 327 (Berthold, Clin Cancer Res 2008) and CALGB trials (Halabi, JCO 2008), the influence of type of pro-gression on outcomes is not well documented in phase III trials with chemotherapy. Here, we investigated the impact of type of progression on OS in mCRPC patients receiving docetaxel-based chemotherapy.
Methods: Data from the phase III study VENICE evaluating docetaxel 75mg/m2q3w 6 aflibercept (Tannock, Lancet Oncol 2013) was used as a training dataset. At randomiza-tion, group 1 (G1) had PSA progression only (n¼ 231), G2 had radiological progres-sion (6 PSA) but no pain (n¼ 348), and G3 had pain (6 PSA, 6 radiological) (n¼ 447). The TAX327 definition for pain was used: Mean present pain intensity 2 and/or mean analgesic score 10 within 7 days prior to randomization (Tannock, NEJM 2004). The impact of type of progression on OS was evaluated in a multivariate Cox regression analysis with backward elimination (5% level), stratified for ECOG per-formance status (0-1 vs 2) and treatment arm.
Results: In the VENICE trial median OS was 28.6 months for G1, 26.3 months for G2 and 16.9 months for G3. Hazard ratios [95% CI] for death were 1.14 [0.92-1.41] in G2
Table: 812P
Baseline characteristics FIRSTANA PROSELICA
D75 (n¼ 391) C20 (n¼ 389) C25 (n¼ 388) C20 (n¼ 598) C25 (n¼ 602)
Median age, years (range) 69.0 (41–87) 68.0 (44–90) 68.5 (42–85) 68.0 (45–89) 69.0 (45–88)
ECOG PS, n (%)
0–1 374 (95.7) 370 (95.1) 376 (96.9) 539 (90.1) 540 (89.7)
2 17 (4.3) 19 (4.9) 12 (3.1) 59 (9.9) 62 (10.3)
Mean PSA, ng/mL (SD) 252.8 (625.2) 213.2 (434.2) 257.9 (578.8) 451.5 (881.0) 444.0 (834.0)
Median present pain intensity, score (range) 1.0 (0.0–4.0) 1.0 (0.0–4.0) 1.0 (0.0–4.0) 1.0 (0.0–5.0) 2.0 (0.0–5.0) Median FACT-P TS (range) 107.4 (41.1–152.0) 107.1 (47.2–151.0) 105.7 (40.1–148.8) 102.8 (37.0–152.8) 101.6 (33.9–150.9)
C20, cabazitaxel 20 mg/m2; C25, cabazitaxel 25 mg/m2; D75, docetaxel 75 mg/m2; ECOG PS, Eastern Cooperative Oncology Group Performance Status; FACT-P TS, Functional Assessment of Cancer Therapy Prostate Total Score; PSA, prostate-specific antigen; SD, standard deviation.
