Category Conference

5559
Efficacy and safety in older patients (pts) with metastatic castration-resistant prostate cancer (mCRPC) receiving cabazitaxel (CBZ) versus abiraterone (ABI) or enzalutamide (ENZ) in the CARD study.

Cora N. Sternberg, Daniel Castellano, Johann S. De Bono, Karim Fizazi, Bertrand F. Tombal, Christian Wu¨lfing, Gero Kramer, Jean-Christophe Eymard, Aristotelis Bamias, Joan Carles, Roberto Iacovelli, Bohuslav Melichar, Asgerdur Sverrisdottir, Christine Theodore, Susan Feyerabend, Carole Helissey, Elizabeth Poole, Ayse Ozatilgan, Christine Geffriaud-Ricouard, Ronald De Wit; Englander Institute of Precision Medicine, Weill Cornell Medicine, New York, NY; Hospital Universitario 12 de Octubre, Madrid, Spain; The Royal Marsden Hospital and The Institute of Cancer Research, London, United Kingdom; Institut Gustave Roussy and University of Paris Sud, Villejuif, France; Institut d Recherche Clinique, Universite´ Catholique de Louvain, Brussels, Belgium; Asklepios Klinik Altona, Hamburg, Abteilung Urologie, Hamburg, Germany; University Clinic for Urology, Vienna, Austria; Jean Godinot Institute, Reims, France; National and Kapodistrian University of Athens, Athens, Greece; Vall d’Hebron Institute of Oncology, Vall d’Hebron University Hospital, Barcelona, Spain; Azienda Ospedaliera Universitaria Integrata (AOUI), Verona, Italy; Fakultni Nemocnice Olomouc/Onkologicka Klinika, Pavlova, Czech Republic; Landspitali University Hospital, Reykjavik, Iceland; Foch Hospital, Suresnes, France; Studienpraxis Urologie, Nu¨rtingen, Germany; Hoˆpital D’Instruction des Arme´ es, Paris, France; Sanofi, Cambridge, MA; Sanofi, Europe Medical Oncology, Paris, France; Erasmus MC, Rotterdam, Netherlands

Background:

In the CARD (NCT02485691) study, radiographic PFS (rPFS), PFS and OS were significantly improved with CBZ vs. androgen-signaling-targeted agents (ARTA; ABI or ENZ) in pts with mCRPC who had received docetaxel (DOC) and progressed within 12 months (mo) on an alternative ARTA. This analysis evaluated the impact of age (, 70 vs. ≥ 70 years) on the efficacy and safety of CBZ and ARTAs in CARD. Methods:255 pts with mCRPC wererandomized 1:1 to CBZ (25 mg/m2 IVQ3W + prednisone [P] + G-CSF) vs. ABI (1000 mg PO + P) or ENZ (160 mg PO) until disease progression, unacceptable toxicity or pt request. Pts were eligible if they had received ≥ 3 cycles of DOC and progressed# 12 mo on the previous alternativeARTA. Primary endpoint wasrPFS. Subgroup analysis of older (≥ 70 years; n = 135) and younger (, 70 years; n = 120) pts was pre-specified for rPFS; others were post hoc.Results:rPFS was significantly improved vs. ARTA in both older (median 8.2 vs. 4.5 mo; HR 0.58; 95% CI 0.38–0.89) and younger pts (median 7.4 vs. 3.2 mo; HR 0.47; 95% CI 0.30–0.74). Median OS for CBZ vs. ARTA was 13.9 vs. 9.4 mo (HR 0.66; 95% CI 0.41–1.06) in older pts and 13.6 vs. 11.8 mo (HR 0.66; 95% CI 0.41–1.08) in younger pts. PFS, tumor, PSA and pain responses also favored CBZ, regardless of age. Grade ≥ 3 adverse events (AEs) occurred in 57.8% vs. 49.3% of older pts receiving CBZ vs. ARTA and 48.4% vs. 42.1% in younger pts. AEs leading to death were more frequent with ARTA, mainly due to disease progression. Conclusions: CBZ had improved efficacy
outcomes vs. ARTA in pts with mCRPC previously treated with DOC and the alternative ARTA, regardless of age. Grade ≥ 3 cardiac AEs were more frequent in older pts treated with ARTA. A higher rateofAEswasreportedinoldervs.youngerpts,forARTAandCBZ.CBZandARTAhaddifferentsafety profiles in older compared with younger pts. Clinical trial information: NCT02485691. Funding: Sanofi. Research Sponsor: Sanofi.

< 70 years ‡ 70 years
CBZ ARTA CBZ ARTA
AEs, % n = 62 n = 57 n = 64 n = 67
Serious AE 32.3 33.3 45.3 43.3
AE leading to death 1.6 7.0 9.4 13.4
Any Grade 3 AE 48.4 42.1 57.8 49.3
>Infection 9.7 5.3 4.7 7.5
> Cardiac disorder 1.6 0.0 0.0 9.0
> Asthenia or fatigue 1.6 3.5 6.3 1.5
> Spinal cord/nerve-root disorder 1.6 3.5 3.1 4.5
> Febrile Neutropenia 3.2 0.0 3.1 0.0

5569
CARD: Overall survival (OS) analysis of patients with metastatic castration-resistant prostate cancer(mCRPC) receiving cabazitaxel versus abiraterone or enzalutamide.

Bertrand F. Tombal, Daniel Castellano, Gero Kramer, Jean-Christophe Eymard, Johann S. De Bono, Cora N. Sternberg, Karim Fizazi, Christian Wulfing, Aristotelis Bamias, Joan Carles, Roberto Iacovelli, Bohuslav Melichar, Asgerdur Sverrisdottir, Christine Theodore, Susan Feyerabend, Carole Helissey, Elizabeth Poole, Ayse Ozatilgan, Christine Geffriaud-Ricouard, Ronald De Wit; Institut d Recherche Clinique, Universite´ Catholique de Louvain, Brussels, Belgium; Hospital Universitario 12 de Octubre, Madrid, Spain; University Clinic for Urology, Vienna, Austria; Jean Godinot Institute, Reims, France; The Royal Marsden Hospital and The Institute of Cancer Research, London, United Kingdom; Englander Institute
of Precision Medicine, Weill Cornell Medicine, New York, NY; Institut Gustave Roussy, University of Paris Sud, Villejuif, France; Asklepios Tumorzentrum Hamburg, Asklepios Klinik Altona, Hamburg, Germany; National and Kapodistrian University of Athens, Athens, Greece; Vall d’Hebron Institute of Oncology, Vall d’Hebron University Hospital, Barcelona, Spain; Azienda Ospe- daliera Universitaria Integrata (AOUI), Verona, Italy; Fakultni Nemocnice Olomouc/Onkologicka Klinika, Pavlova, Czech Republic; Landspitali University Hospital, Reykjavik, Iceland; Foch Hospital, Suresnes, France; Studienpraxis Urologie, Nu¨ rtingen, Germany; Hoˆ pital D’Instruction des Arme´ es, Paris, France; Sanofi, biostatistics, Cambridge, MA; Sanofi, Global Medical Oncology, Cambridge, MA; Sanofi, Europe Medical Oncology, Paris, France; Erasmus MC, Rotterdam, Netherlands

Background:

The CARD trial (NCT02485691) compared cabazitaxel vs. an androgen receptor targeted agent (ART; abiraterone/enzalutamide) in mCRPC previously treated with docetaxel and the alternative ART (abiraterone/enzalutamide), in any order. These post hoc analyses assessed OS from various time points and the impact of prognostic factors. Methods: Patients with mCRPC previously treated with docetaxel and progressing # 12 months on prior abiraterone/enzalutamide were randomized 1:1 to cabazitaxel(25mg/m2 IVQ3W+dailyprednisone+prophylacticG-CSF)vs.abiraterone(1000mgPO+ dailyprednisone)orenzalutamide(160mgPO).OSwas calculatedfromdateofdiagnosisofmetastatic disease, date of mCRPC, and start of 1st, 2nd or 3rd life-extending therapy (LET). A stratified multivariate Cox regression analysis assessed the impact of 14 prognostic factors on OS using a stepwise model selection approach with a significance level of 0.10 for entry into the model and 0.05 for removal. Results: In the CARD study (N = 255), median OS was longer with cabazitaxel vs. abiraterone/enzalutamide (13.6 vs 11.0 months; HR 0.64, 95% CI 0.46–0.89; p = 0.008). OS was numerically improved for cabazitaxel vs. abiraterone/enzalutamide when assessed from the time of diagnosis of metastatic disease or mCRPC, or from start of 1st or 2nd LET (Table). In the multivariate analysis,lowhemoglobin,highbaselineneutrophiltolymphocyteratio,andhighPSAvaluesatbaseline wereassociated withworse OS. In presence of these factors,theOSbenefit observed with cabazitaxel versus abiraterone/enzalutamide remained significant (HR 0.63, 95% CI 0.42–0.94, p = 0.022). Conclusions: Cabazitaxel numerically improved OS vs. abiraterone/enzalutamide in patients with mCRPC previously treated with docetaxel and the alternative ART (abiraterone/enzalutamide), what- ever the time point considered. The robustness of this OS benefit was confirmed by stratified multivariate analysis. Sanofi funded. Clinical trial information: NCT02485691. Research Sponsor: Sanofi.

< 70 years ‡ 70 years
CBZ ARTA CBZ ARTA
AEs, % n = 62 n = 57 n = 64 n = 67
Serious AE 32.3 33.3 45.3 43.3
AE leading to death 1.6 7.0 9.4 13.4
Any Grade 3 AE 48.4 42.1 57.8 49.3
>Infection 9.7 5.3 4.7 7.5
> Cardiac disorder 1.6 0.0 0.0 9.0
> Asthenia or fatigue 1.6 3.5 6.3 1.5
> Spinal cord/nerve-root disorder 1.6 3.5 3.1 4.5
> Febrile Neutropenia 3.2 0.0 3.1 0.0