Eisenberger, M.A. (Mario)

Mercier, F. (F.)

Oudard, S. (Stéphane)

Robbrecht, D.G. (D. G.)

Soest, R.J. (Robert Jan) van

Tannock, I.F. (Ian)

Tombal, B. (Bertrand)

Wit, R. (Ronald) de

Erasmus University Digital Repository

Editorial acknowledgement: Editorial assistance was provided by Danielle Lindley ofMeditech 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, InnocrinPharma, 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) inpatients with metastatic castration-resistant prostate cancer (mCRPC)receiving cabazitaxel in the phase III PROSELICA and FIRSTANA trialsA. Thiery Vuillemin1, K. Fizazi2, O. Sartor3, S. Oudard4, D. Bury5, S. Guillonneau6,A. Ozatilgan7, M. Eisenberger8, J.S. de Bono91Medical Oncology, Centre Hospitalier Régional Universitaire, Besancon, France,2Cancer Medicine, Institut Gustave Roussy, Villejuif, France, 3Medicine and Urology,Tulane Cancer Centre, New Orleans, LA, USA, 4George Pompidou European Hospital,René Descartes University, Paris, France, 5Real World Evidence/Global ClinicalOutcomes, Sanofi US, Cambridge, MA, USA, 6Biostatistics, Sanofi, Chilly-Mazarin,France, 7Global Medical Oncology, Sanofi US, Cambridge, MA, USA, 8The SidneyKimmel Comprehensive Cancer Center, Johns Hopkins Hospital, Baltimore, MD, USA,9Division of Clinical Studies Drug Development Unit, Royal Marsden NHS FoundationTrust/The Institute of Cancer Research, Sutton, UKBackground: PROSELICA (NCT01308580) assessed the non-inferiority of cabazitaxel20 mg/m2 (C20) vs 25 mg/m2 (C25) in patients (pts) with mCRPC post docetaxel, whileFIRSTANA (NCT01308567) investigated whether C20 and C25 were superior to doce-taxel 75 mg/m2 (D75) in chemotherapy-naive mCRPC. This analysis evaluated theimpact of cabazitaxel on HRQL in both trials.Methods: Alongside pain and analgesic score, HRQL was assessed using the FunctionalAssessment of Cancer Therapy Prostate (FACT-P) questionnaire. The analysis focusedon 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% and59.4% 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, n¼ 266;FIRSTANA C20 11.7, n¼ 206; C25 11.7, n¼ 202; D75 9.0, n¼ 195); these were largelymaintained. For pts with a pain response in PROSELICA, FACT-P TS improvementsoccurred as early as C1 (C20 6.8, n¼ 71; C25 11.1, n¼ 81) and were maintained untilC8 (C20 10.6, n¼ 43; C25 9.6, n¼ 44). In FIRSTANA, FACT-P TS improvements inpts 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, n¼ 32) and maintained until C9 (C20 9.0, n¼ 27; C25 10.5, n¼ 26;D75 16.4, n¼ 20). In pts with a tumor or PSA response, HRQL was maintained for alltreatment arms in both studies. Additional results for clinical responder subgroups andFACT-P subscales will be presented.Conclusions: More than half of the pts experienced HRQL improvements, which weremaintained. 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 ofMediTech 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: BellicumPharmaceuticals, Dendreon; Advisor and expenses: Bayer, Johnson & Johnson,Medivation, Oncogenex, Sanofi, Tokai Pharmaceuticals, AstraZeneca, Progenics;Institute: funding: Bayer, Johnson & Johnson, Sanofi, Dendreon, Endocyte, InnocrinPharma, 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 onabiraterone acetate with prednisone.813P Treatment of metastatic castration-resistant prostate cancer (mCRPC);Survival by type of progression at initiation of treatmentD.G. Robbrecht1, R.J. van Soest2, I.F. Tannock3, S. Oudard4, B. Tombal5, M. Eisenberger6,F. Mercier7, R. de Wit11Medical Oncology, Erasmus MC Daniel den Hoed Cancer Center, Rotterdam,Netherlands, 2Urology, Erasmus MC Daniel den Hoed Cancer Center, Rotterdam,Netherlands, 3Medical Oncology, Princess Margaret Hospital, Toronto, ON, Canada,4Immunothérapie et Traitement Antiangiogénique en Pathologie Cancérologique,Hopital European George Pompidou, Paris, France, 5Urology, Cliniques Universitaires St.Luc, Brussels, Belgium, 6Medical Oncology, Johns Hopkins Sidney Kimmel CancerCenter, Baltimore, MD, USA, 7Stat Process, Sanofi, Charlotte, Nc, FranceBackground: The usual sequence of progression events in mCRPC patients treatedwith new hormonal agents is known: PSA progression, followed by radiological pro-gression and finally pain progression (Ryan, NEJM 2013; Beer, NEJM 2014). Althoughpain was associated with poor overall survival (OS) in the TAX 327 (Berthold, ClinCancer 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 patientsreceiving docetaxel-based chemotherapy.Methods: Data from the phase III study VENICE evaluating docetaxel 75mg/m2 q3w 6aflibercept (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 2and/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 multivariateCox 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 G2and 16.9 months for G3. Hazard ratios [95% CI] for death were 1.14 [0.92-1.41] in G2Table: 812PBaseline characteristics FIRSTANA PROSELICAD75 (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.Annals of Oncology abstractsVolume 29 | Supplement 8 | October 2018 doi:10.1093/annonc/mdy284 | viii281This is an Open Access article under the  CC-BY-NC license.-NDand 2.13 [1.75 - 2.59] in G3 compared to G1. In multivariate analysis, pain at random-ization was the strongest predictor of poor OS: HR 1.71, 95% CI 1.39-2.11, vs PSA pro-gression only. Other significant prognostic factors included older age, high alkalinephosphatase, short duration of first androgen deprivation therapy, low hemoglobinlevel and high neutrophil-lymphocyte ratio. Docetaxel led to 50% decline in PSA in67.5%, 80.5% and 77% in G1, G2 and G3 respectively.Conclusions: The type of progression at initiation of first-line chemotherapy inmCRPC is prognostic. Patients with pain at initiation of chemotherapy had a medianOS of1 year shorter than those having PSA progression only. Validation of theseresults by an independent dataset (TAX 327) is ongoing. Results will be presented atESMO.Legal entity responsible for the study: Sanofi.Funding: Sanofi.Disclosure: R.J. van Soest: Honoraria: Astellas, Sanofi, Janssen. I.F. Tannock: Datamonitoring reimburse: Janssen, Roche. S. Oudard: Personal fees: Sanofi, Janssen,Astellas. B. Tombal: Advisor, investigator: Sanofi-aventis; Janssen Pharmaceuticals,Inc., Takeda, Astellas, Pharma, Inc., Kyocyt. M. Eisenberger: Consultancy: Sanofi. F.Mercier: Research funding: Sanofi. R. de Wit: Consultant: Sanofi, Merck, Roche;Speaker fees: Merck. All other authors have declared no conflicts of interest.814P Platinum-based therapy in men with metastatic castration resistantprostate (mCRPC) with or without DNA repair defects: A multicentreretrospective analysisS. Gillessen1, S. Schmid2, H. Beltran3, D.V.P. Almeida4, N. Mehra5, P. Lavaud6, R. MoralesBarrera7, D. Pignataro8, E. Castro Marcos9, V. Conteduca3, E. Efstathiou10, H.M.L. Le11,C.V. Pezaro12, H. Suzuki13, A. Zivi14, D. Klingbiel15, A.G. Omlin161Division of Cancer Sciences, University of Manchester and the Christie, Manchester, UKand Division of Medical Oncology and Haematology, Kantonsspital St. Gallen, St.Gallen, University of Bern, Switzerland, 2Oncology and Haematology, Kantonsspital St.Gallen, St. Gallen, Switzerland, 3Division of Hematology and Medical Oncology, WeillCornell Medical College, New York, NY, USA, 4Oncology, Hospital S~ao Jose -Beneficencia Portuguesa de S~ao Paulo, S~ao Paulo, Brazil, 5Oncology, RadboudUniversity Medical Centre Nijmegen, Nijmegen, Surrey, Netherlands, 6Department ofMedical Oncology, IGR - Insitut Gustave Roussy, Villejuif, France, 7Department ofMedical Oncology, Vall d’Hebron University Hospital, Barcelona, Spain, 8MedicalOncology, Azienda Ospedaliera Universitaria San Luigi Gonzaga, Orbassano, Italy,9Prostate Cancer Unit, CNIO- Spanish National Cancer Center, Madrid, Spain,10Genitourinary Medical Oncology, The University of Texas MD Anderson CancerCenter, Houston, TX, USA, 11Medical Oncology, Guy’s and St.Thomas Hospital, London,United Arab Emirates, 12Oncology, Eastern Health, Box Hill, Australia, 13Urology, TohoUniversity Sakura Medical Center, Tokio, Japan, 14Oncology, Ospedale dell’Angelo,Mestre, Venice, Italy, 15Swiss Group for Clinical Cancer Research Coordinating Center,SAKK, Bern, Switzerland, 16Medical Onocolgy and Haematology, KantonsspitalSt. Gallen, St. Gallen, SwitzerlandBackground: Platinum compounds have been tested in a larger number of mostly smallto medium sized clinical trials in molecularly unselected prostate cancer patients (pts).Advances in castration-resistant prostate cancer (CRPC) molecular profiling haveshown that a significant proportion of pts harbor DNA repair defects, which may serveas predictive markers for sensitivity to platinum agents. Our aim was to evaluate theantitumour activity of platinum agents in a contemporaneous mCRPC cohort with orwithout DNA repair defects.Methods: International, multicenter retrospective database project in 14 centers world-wide. Pts with mCRPC treated with a platinum agent were included. Pts with primarypure small cell carcinoma and/or insufficient outcome data were excluded. For antitu-mour activity PSA levels at baseline, after 4-, 8- and 12-weeks of therapy (tx) were ana-lyzed as well as soft tissue response and duration of platinum-based chemotherapy.Overall survival (OS) was analyzed by Kaplan Meier method.Results: A total of 167 pts have been included in this analysis, 33 (20%) received plati-num monotherapy, 134 (80%) a platinum combination therapy. Carboplatin was usedin 140 (84%), cisplatin in 26 (16%) of pts. Combination tx with etoposise was used in45 (27%), paclitaxel in 35 (21%) and docetaxel in 28 (17%) of pts. At start of platinumtx median age was 68 years, median PSA 78 ug/l, median ALP 185 U/l, median hemo-globin 103 g/l. The metastatic sites at start of platinum therapy were: bone 84%, lymphnode 59% and visceral 60%. Outcome data by DNA repair defect status are summar-ized in the table.Table: 814POutcome of platinumbased txDNA repairdefects:assessed,presentN¼ 40DNA repairdefects:assessed,not presentN¼ 42DNA repairdefects notassessedN¼ 85N (%) N (%) N (%)PSA decline 50% 13/32 (41) 8/23 (35) 24/73 (33)Soft tissue response (PR/CR) 9/32 (28) 7/29 (24) 16/48 (33)median time on platinumtx: months (m),interquartile range (IQR)2.5m(IQR 1.8-5.9)2.8m(IQR 1.4 – 4.6)3.5m(IQR 1.4 – 4.6)OS from start of platinumtherapy (m, IQR)9.1m(IQR 4.8 – NR)11m(IQR 6.7-22)12m(IQR 7-29)Conclusions: In this retrospective analysis of a contemporary cohort of men withmCRPC and poor prognostic characteristics platinum-based treatment seems to havesignificant anti-tumor activity irrespective of DNA repair status. Comparison of sub-groups is limited by small sample size. Updated analyses will be presented.Legal entity responsible for the study: Ethical Committee St. Gallen.Funding: Has not received any funding.Disclosure: S. Gillessen: Advisory boards (compensated): IDMC, AAA International,Active Biotech AB IDMC, Astellas Pharma, Bayer, Bristol-Myers Squibb, Clovis,Curevac, Dendreon Corporation, Ferring, Innocrin Pharmaceuticals, Janssen Cilag,MaxiVAX SA, Millennium Pharmaceuticals, Orion, Roche, Sanofi Aventis Group;Advisory boards (uncompensated): Astellas Pharma, Bayer, ESSA PharmaceuticalsCorp., Nectar, ProteoMediX, Sanofi; Speakers Bureau (compensated): Janssen,Novartis; Speakers bureau (uncompensated): Astellas Pharma, Janssen, Sanofi AventisGroup; Patent pending patent application for a method for biomarker WO2009138392 A. H. Suzuki: Steering Committee: ACIS (ARN-509); Lead PrincipleInvestigator: ARASENS (ODM-201); Advisory board: AstraZeneca, Bayer, Janssen,Nihon Medi-Physics, Kissei; Research funding: Takeda, Bayer, Astellas, Daiichi-Sankyo, Pfizer, Nihon Kayaku Ono; Honoraria: Astellas, AstraZeneca, Daiichi Sankyo,Janssen, Pfizer, Novartis, Sanofi, Takeda. A.G. Omlin: Advisory role (compensated,institutional): AstraZeneca, Astellas, Bayer, Janssen, Molecular Partners, MSD, Pfizer,Roche, Sanofi Aventis; Research support (institutional): TEVA, Janssen; Travel sup-port: Astellas, Bayer, Janssen, Sanofi, Aventis. All other authors have declared no con-flicts of interest.815P Symptomatic skeletal related events (SSE) and SSE-free-survival in realworld castration-resistant prostate cancer (CRPC) patients: Resultsfrom CAPRIM. Kuppen1, H.M. Westgeest2, A.J.M. van den Eertwegh3, J. Van Moorselaar4,N. Mehra5, I. van Oort6, A.C.M. van den Bergh7, J.L. Coenen8, K.K.H. Aben9,R. Somford10, J. Lavalaye11, A. Bergman12, C.A. Uyl-de Groot13, W.R. Gerritsen51Institute for Medical Technology Assessment, Erasmus School of Health Policy andManagement, Rotterdam, Netherlands, 2Medical Oncology, Amphia Ziekenhuis, Breda,Netherlands, 3Medical Oncology, Vrije University Medical Centre (VUMC), Amsterdam,Netherlands, 4Urology, Vrije University Medical Centre (VUMC), Amsterdam,Netherlands, 5Medical oncology, Radboud University Medical Centre Nijmegen,Nijmegen, Netherlands, 6Urology, Radboud University Medical Centre Nijmegen,Nijmegen, Netherlands, 7Radiation oncology, UMCG, Groningen, Netherlands, 8MedicalOncology, Isala Klinieken, Zwolle, Netherlands, 9IKNL, Comprehensive Cancer Centre,Nijmegen, Netherlands, 10Urology, Canisius Wilhelmina Ziekenhuis, Nijmegen,Netherlands, 11Nuclear Medicine, Antonius Ziekenhuis, Nieuwengein, Netherlands,12Division of Internal Medicine (MOD) and Oncogenomics, Division of Internal Medicine(MOD) and Oncogenomics, Amsterdam, Netherlands, 13Institute of Health Policy &Management, Institute for Medical Technology Assessment, Erasmus University,Rotterdam, NetherlandsBackground: Bone metastases are common in CRPC patients and these patients (pts)are at risk for symptomatic skeletal related events (SSE). Bone directed therapy andearly initation of a life-prolonging drug (LPD) therapy can prevent or prolong time toSSEs. The objective is to evaluate whether delay in LPD has adverse outcome in CRPCpts and a shorter SSE-free interval.Methods: CAPRI is an investigator-initiated, observational study in 20 hospitals in theNetherlands. All treated CRPC pts are retrospectively included in subgroups based ontype of first line treatment: LPD (docetaxel, abiraterone, enzalutamide or radium-223)or non-LPD (other drugs as anti-androgens, prednisone). SSEs are defined as theoccurrence of either radiotherapy (RT) to the bone, surgery to the bone, pathologicalfracture or spinal cord compression (SCC).Results: 1,618 pts were included in this analysis. Median follow-up was 26 months(IQR 15-39). 466 (29%) were treated with LPD (mostly docetaxel 15%) and 1,152abstracts Annals of Oncologyviii282 | Genitourinary tumours, prostate Volume 29 | Supplement 8 | October 2018

Treatment of metastatic castration-resistant prostate cancer (mCRPC); Survival by type of progression at initiation of treatment

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Treatment of metastatic castration-resistant prostate cancer (mCRPC); Survival by type of progression at initiation of treatment

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