Dutta, S.

Halabi, S.

Kelly, W.

Morris, M. J.

Ryan, C. J.

Taplin, M-E.

English

Jefferson Digital Commons

Thomas Jefferson University Jefferson Digital Commons Department of Medical Oncology Faculty Papers Department of Medical Oncology 10-2018 Androgen decline and outcome in castration resistant prostate cancer(mCRPC) patients treated with docetaxel (Doc), prednisone1/-bevacizumab (B) C. J. Ryan S. Dutta W. Kelly M. J. Morris M-E. Taplin See next page for additional authors Follow this and additional works at: https://jdc.jefferson.edu/medoncfp  Part of the Oncology Commons Let us know how access to this document benefits you This Article is brought to you for free and open access by the Jefferson Digital Commons. The Jefferson Digital Commons is a service of Thomas Jefferson University's Center for Teaching and Learning (CTL). The Commons is a showcase for Jefferson books and journals, peer-reviewed scholarly publications, unique historical collections from the University archives, and teaching tools. The Jefferson Digital Commons allows researchers and interested readers anywhere in the world to learn about and keep up to date with Jefferson scholarship. This article has been accepted for inclusion in Department of Medical Oncology Faculty Papers by an authorized administrator of the Jefferson Digital Commons. For more information, please contact: JeffersonDigitalCommons@jefferson.edu. Authors C. J. Ryan, S. Dutta, W. Kelly, M. J. Morris, M-E. Taplin, and S. Halabi (71%) with non-LPD (mostly bicalutamide 62%) in first line. In the non-LPD sub-group, LPD was postponed in 712 patients. The LPD subgroup had frequent bonemetastases, worse ECOG and, higher LDH, ALP and PSA at the start of first line ther-apy. 36% of all patients experienced a SSE during follow-up (32% RT to the bone, 4%surgery to the bone, 4% pathological fracture and 6% SCC). There was a small differ-ence in total SSEs between subgroups (39% for LPD vs 35% for non-LPD, p¼ 0.064).Median SSE-free survival was 13.0 vs 21.2 months for LPD and non-LPD respectively(HR 1.626, p¼ 0.007). Correction for prognostic factors showed that type of first linetherapy (LPD/non-LPD) was not associated with SSE-free survival (HR 1.021,p¼ 0.817). Worse ECOG and presence of bone metastases were significant predictorsfor worse SSE-free survival.Conclusions: Approximately 40% of CRPC-patients developed a SSE during follow-up.Worse patient and disease characteristics probably influenced timing of LPD. Thesefactors were also related with worse SSE-free survival. Delay in the initiation of a LPD atcastration-resistant state does not appear to influence outcome related to time-to-SSE.Clinical trial identification: The CAPRI study is registered in the Dutch Trial Registryas NTR3591.Legal entity responsible for the study: Institute for Medical Technology Assessment,Erasmus University Rotterdam.Funding: The CAPRI registry was funded by Sanofi-Aventis Netherlands B.V., Janssen-Cilag B.V., Astellas Pharma B.V., and Bayer B.V. The funding organizations had no rolein the design and conduct of the study, collection, management, analysis, interpretationof the data, and preparation, review, or approval of the abstract.Disclosure: A.J.M. van den Eertwegh: Study grant, travel expenses ASCO: Sanofi.Speaker fee, advisory board: Astellas. J. VanMoorselaar: Receipt of grants/researchsupports: Astellas, Ferring, Ipsen; Honoraria, consultation fees: Amgen, Astellas,AstraZeneca, Bayer, Janssen, Sanofi-Genzyme. I. van Oort: Conflict of interest: Astellas,Janssen, Sanofi, Bayer. J.L. Coenen: Advisory board: Sanofi. A. Bergman: PI of one ofthe IIS sponsored by Sanofi. W.R. Gerritsen: Speaker fees: Astellas, Bavarian Nordic,Bristol-Myers Squibb, MSD, Janssen-Cilag; Advisory boards: Amgen, Astellas, Bayer,Bristol-Myers Squibb, Curevac, Dendreon, Janssen-Cilag, Merck (MSD), Morphosys,Sanofi; Ad hoc consultancy: Aglaia Biomedical Ventures, Psioxus Therapeutics. Allother authors have declared no conflicts of interest.816P Androgen decline and outcome in castration resistant prostate cancer(mCRPC) patients treated with docetaxel (Doc), prednisone 1/-bevacizumab (B)C.J. Ryan1, S. Dutta2, W. Kelly3, M.J. Morris4, M-E. Taplin5, S. Halabi61Division of Hematology, Oncology and Transplantation, Masonic Cancer Center,Minneapolis, MN, USA, 2Department of Biostatistics and Bioinformatics, DukeUniversity, Durham, NC, USA, 3Medicine, Thomas Jefferson University, Philadelphia, PA,USA, 4Medicine, Memorial Sloan-Kettering Cancer Center, New York, NY, USA, 5LankCenter for Genitourinary Oncology, Dana-Farber Cancer Institute, Boston, MA, USA,6Biostatistics and Bioinformatics, Duke University, Durham, NC, USABackground: Androgen levels are associated with overall survival (OS) in mCRPC. Docimpairs microtubules and has AR inhibitory effects. This analysis evaluates change inandrogen levels (Testosterone (T), Androstenedione (A) and DHEA (D) and outcomein Doc-treated mCRPC patients.Methods:Data from 1,050men treated on CALGB 90401 with Doc, prednisone andeither B or placebo were used. Pre-treatment, 6 week and progression serum assays forT, A and Dwere performed via tandem Liquid Chromatography-Mass Spectrometry(LC-MS/MS). Ratio of change in androgen (6 week value /baseline value) was calcu-lated. Decline was further evaluated as high or low (> or<median decline for allpatients). The logistic regression and proportional hazards models were used to assessthe prognostic significance of changes in T, A, and D in predicting PSA response, PFSand OS adjusting for known prognostic factors.Results:Median values for baseline T, A, and, D were 1.0, 13.5 and 8.1, ng/dL respec-tively, while androgen levels at 6 weeks were 0.64, 7.0 and 6.8, ng/dL respectively. At 6weeks a decline in all three androgens was observed. The ratio of 6weeks/baseline in T,A and Dwere 0.93, 0.56 and 0.86, respectively. There was interaction between levels ofT decline and treatment arm (p-value¼0.047). Among 291 patients with high levels ofT decline, those who also received B were more likely to experience a 50% decline inPSA (87%) compared to those who did not receive B (67%,). Associations betweenandrogen decline and PFS were NS. Inmultivariable analysis adjusting for prognosticfactors, the hazard ratio (HR) for OS demonstrated that decline in T at 6-weeks/base-line was associated with longer OS, HR 1.02 (95% CI 1.01 ,1.03 p¼ 0.001). Median OSfor low T change (ratio>¼0.93) is 20.9 mos vs 26.3 mos for high T change (<0.93).Conclusions: Patients treated with Doc who experience a greater drop in T on therapyexperience a significantly longer OS and higher rate of PSA decline but no effect onPFS. B and androgen decline may confer interacting beneficial effects. Data are consis-tent with the favorable prognostic significance of higher serum androgens in the CRPCsetting and reflecting the potential effect of Doc on AR signalling.Clinical trial identification:NCT00110214.Legal entity responsible for the study:Alliance for Clinical Trials in Oncology.Funding:National Cancer Institute: R21 CA195424-01, U10CA180821, U10CA180882.Disclosure: C.J. Ryan: Consulting fees: Sanofi. All other authors have declared no con-flicts of interest.817P Cabazitaxel treatment in metastatic castration-resistant prostatecancer (mCRPC) clinical trials compared to usual care in CAPRI: Anobservational study in the NetherlandsH.M. Westgeest1, M. Kuppen2, 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, R. de Wit11, A. Bergman12, J. Lavalaye13, C.A. Uyl-de Groot14,W.R. Gerritsen51Medical Oncology, Amphia Ziekenhuis, Breda, Netherlands, 2Institute for MedicalTechnology Assessment, Erasmus School of Health Policy and Management,Rotterdam, Netherlands, 3Medical Oncology, VU Medical Center, 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, Netherlands ComprehensiveCancer Organisation, Utrecht, Netherlands, 10Urology, Canisius Wilhelmina Ziekenhuis,Nijmegen, Netherlands, 11Medical Oncology, Erasmus MC Daniel den Hoed CancerCenter, Rotterdam, Netherlands, 12Division of Internal Medicine (MOD) andOncogenomics, The Netherlands Cancer Institute Antoni van Leeuwenhoek Hospital,Amsterdam, Netherlands, 13Nuclear Medicine, Antonius Ziekenhuis, Nieuwengein,Netherlands, 14Institute for Medical Technology Assessment, Erasmus UniversityRotterdam, Rotterdam, NetherlandsBackground: Cabazitaxel (CAB) has been shown in the TROPIC trial to improve over-all survival (OS) in mCRPC patients after docetaxel (DOC). However clinical trial pop-ulations may not reflect the real world population. The objective is to compare patientcharacteristics and outcome of CAB within clinical trials and in standard of care (SOC)from data extracted from the CAPRI registry.Methods: CRPC pts treated with CAB directly after DOC, before 1-1-2017, eitherwithin a clinical trial or as SOC were retrospectively identified and followed to 1-1-2018. For multivariable analyses, missing values were imputed bymultiple imputationusing theMonte CarloMarkov Chain method.Results:Table: 817P Baseline characteristics at start cabazitaxel (baselineperiod defined as 42 days before to 7 days after start of cabazitaxel).Total perceAge (years) Median (IQR)75 years (%)68 (64-72) 17 67 (64-72) 13 0.502Period on ADT (months)Median (IQR)25 (18-37) 30 (19-45) 0.091ALP (U/L) Median (IQR)Missing (%)222 (100-360) 18 192 (97-366) 11 0.799PSA (ug/L) Median (IQR)Missing (%)200 (65-567) 12 209 (79-500) 8 0.711Hemoglobin (mmol/L)Median (IQR) Missing(%)7.1 (6.3-7.8) 17 7.7 (6.7-8.1) 11 0.029LDH (U/L) Median (IQR)Missing (%)328 (252-504) 26 268 (209-397 14) 0.010ECOG performance (%) 0 1>1 Missing16 49 9 27 23 56 3 17 0.186Visceral disease (%) No YesMissing29 19 52 45 11 44 0.038Opioid use (%) No YesMissing23 28 50 41 27 33 0.140Symptoms (%) No YesMissing6 78 16 17 72 11 0.033Docetaxel cycles Median(IQR) Missing (%)7 (5-10) 1 10 (7-10) 3 0.002Time since last docetaxeldose (months) Median(IQR) <6 months (valid%) Missing (%)2.2 (0.9-4.7) 86 5 3.9 (2.0-6.0) 74 5 0.001Annals of Oncology abstractsVolume 29 | Supplement 8 | October 2018 doi:10.1093/annonc/mdy284 | viii283This is an Open Access article under the  CC-BY-NC license.-ND

Androgen decline and outcome in castration resistant prostate cancer(mCRPC) patients treated with docetaxel (Doc), prednisone1/-bevacizumab (B)

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Androgen decline and outcome in castration resistant prostate cancer(mCRPC) patients treated with docetaxel (Doc), prednisone1/-bevacizumab (B)

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