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.
Annals of Oncology
abstracts
Volume 29 | Supplement 8 | October 2018
doi:10.1093/annonc/mdy284 | viii281
and 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 alkaline phosphatase, short duration of first androgen deprivation therapy, low hemoglobin level and high neutrophil-lymphocyte ratio. Docetaxel led to 50% decline in PSA in 67.5%, 80.5% and 77% in G1, G2 and G3 respectively.
Conclusions:The type of progression at initiation of first-line chemotherapy in mCRPC is prognostic. Patients with pain at initiation of chemotherapy had a median OS of1 year shorter than those having PSA progression only. Validation of these results by an independent dataset (TAX 327) is ongoing. Results will be presented at ESMO.
Legal entity responsible for the study:Sanofi. Funding:Sanofi.
Disclosure:R.J. van Soest: Honoraria: Astellas, Sanofi, Janssen. I.F. Tannock: Data monitoring 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 resistant prostate (mCRPC) with or without DNA repair defects: A multicentre retrospective analysis S. Gillessen1 , S. Schmid2 , H. Beltran3 , D.V.P. Almeida4 , N. Mehra5 , P. Lavaud6 , R. Morales Barrera7 , D. Pignataro8 , E. Castro Marcos9 , V. Conteduca3 , E. Efstathiou10 , H.M.L. Le11 , C.V. Pezaro12 , H. Suzuki13 , A. Zivi14 , D. Klingbiel15 , A.G. Omlin16 1
Division of Cancer Sciences, University of Manchester and the Christie, Manchester, UK and Division of Medical Oncology and Haematology, Kantonsspital St. Gallen, St. Gallen, University of Bern, Switzerland,2
Oncology and Haematology, Kantonsspital St. Gallen, St. Gallen, Switzerland,3
Division of Hematology and Medical Oncology, Weill Cornell Medical College, New York, NY, USA,4
Oncology, Hospital S~ao Jose -Beneficencia Portuguesa de S~ao Paulo, S~ao Paulo, Brazil,5
Oncology, Radboud University Medical Centre Nijmegen, Nijmegen, Surrey, Netherlands,6
Department of Medical Oncology, IGR - Insitut Gustave Roussy, Villejuif, France,7
Department of Medical Oncology, Vall d’Hebron University Hospital, Barcelona, Spain,8
Medical Oncology, Azienda Ospedaliera Universitaria San Luigi Gonzaga, Orbassano, Italy, 9
Prostate Cancer Unit, CNIO- Spanish National Cancer Center, Madrid, Spain, 10
Genitourinary Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA,11
Medical Oncology, Guy’s and St.Thomas Hospital, London, United Arab Emirates,12
Oncology, Eastern Health, Box Hill, Australia,13
Urology, Toho University Sakura Medical Center, Tokio, Japan,14
Oncology, Ospedale dell’Angelo, Mestre, Venice, Italy,15
Swiss Group for Clinical Cancer Research Coordinating Center, SAKK, Bern, Switzerland,16
Medical Onocolgy and Haematology, Kantonsspital St. Gallen, St. Gallen, Switzerland
Background: Platinum compounds have been tested in a larger number of mostly small to medium sized clinical trials in molecularly unselected prostate cancer patients (pts). Advances in castration-resistant prostate cancer (CRPC) molecular profiling have shown that a significant proportion of pts harbor DNA repair defects, which may serve as predictive markers for sensitivity to platinum agents. Our aim was to evaluate the antitumour activity of platinum agents in a contemporaneous mCRPC cohort with or without 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 primary pure 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 platiplati-num combination therapy. Carboplatin was used in 140 (84%), cisplatin in 26 (16%) of pts. Combination tx with etoposise was used in 45 (27%), paclitaxel in 35 (21%) and docetaxel in 28 (17%) of pts. At start of platinum tx 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%, lymph node 59% and visceral 60%. Outcome data by DNA repair defect status are summar-ized in the table.
Table: 814P Outcome of platinum based tx DNA repair defects: assessed, present N¼ 40 DNA repair defects: assessed, not present N¼ 42 DNA repair defects not assessed N¼ 85 N (%) N (%) N (%) PSA decline50% 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 platinum
tx: 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 platinum
therapy (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 with mCRPC and poor prognostic characteristics platinum-based treatment seems to have significant 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 Pharmaceuticals Corp., Nectar, ProteoMediX, Sanofi; Speakers Bureau (compensated): Janssen, Novartis; Speakers bureau (uncompensated): Astellas Pharma, Janssen, Sanofi Aventis Group; Patent pending patent application for a method for biomarker WO 2009138392 A. H. Suzuki: Steering Committee: ACIS (ARN-509); Lead Principle Investigator: 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 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 real world castration-resistant prostate cancer (CRPC) patients: Results from CAPRI
M. 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. Gerritsen5 1
Institute for Medical Technology Assessment, Erasmus School of Health Policy and Management, Rotterdam, Netherlands,2
Medical Oncology, Amphia Ziekenhuis, Breda, Netherlands,3
Medical Oncology, Vrije University Medical Centre (VUMC), Amsterdam, Netherlands,4
Urology, Vrije University Medical Centre (VUMC), Amsterdam, Netherlands,5
Medical oncology, Radboud University Medical Centre Nijmegen, Nijmegen, Netherlands,6
Urology, Radboud University Medical Centre Nijmegen, Nijmegen, Netherlands,7
Radiation oncology, UMCG, Groningen, Netherlands,8 Medical Oncology, Isala Klinieken, Zwolle, Netherlands,9
IKNL, Comprehensive Cancer Centre, Nijmegen, Netherlands,10
Urology, Canisius Wilhelmina Ziekenhuis, Nijmegen, Netherlands,11
Nuclear Medicine, Antonius Ziekenhuis, Nieuwengein, Netherlands, 12
Division of Internal Medicine (MOD) and Oncogenomics, Division of Internal Medicine (MOD) and Oncogenomics, Amsterdam, Netherlands,13
Institute of Health Policy & Management, Institute for Medical Technology Assessment, Erasmus University, Rotterdam, Netherlands
Background: Bone metastases are common in CRPC patients and these patients (pts) are at risk for symptomatic skeletal related events (SSE). Bone directed therapy and early initation of a life-prolonging drug (LPD) therapy can prevent or prolong time to SSEs. The objective is to evaluate whether delay in LPD has adverse outcome in CRPC pts and a shorter SSE-free interval.
Methods: CAPRI is an investigator-initiated, observational study in 20 hospitals in the Netherlands. All treated CRPC pts are retrospectively included in subgroups based on type of first line treatment: LPD (docetaxel, abiraterone, enzalutamide or radium-223) or non-LPD (other drugs as anti-androgens, prednisone). SSEs are defined as the occurrence of either radiotherapy (RT) to the bone, surgery to the bone, pathological fracture 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 1,152
