2535 Clinical outcomes in chemotherapy-naïve metastatic castrationresistant prostate cancer (mCRPC) patients (pts) treated with abiraterone acetate (ABI) stratified by prognosis

S486 2533 POSTER Intra-operative margin detection using Cerenkov luminescence Imaging during radical prostatectomy − initial results from the PRIME study C. Michel1 , A. Freeman2 , C. Jameson2 , W. Waddington3 , D. Tuch4 , M. Harboe4 , P. Cathcart1 . 1 University College London Hospitals, Surgical Urology, London, United Kingdom; 2 University College London Hospitals, Pathology, London, United Kingdom; 3 University College London Hospitals, Nuclear Medicine, London, United Kingdom; 4 Lightpoint Medical Ltd, London, United Kingdom Background: Cerenkov Luminescence Imaging (CLI) is a new imaging technology for intra-operative assessment of surgical margins and lymph nodes status, based on optical imaging of PET radiopharmaceuticals. The PRIME (PRostate Imaging for Margin Evaluation) study is currently being conducted to evaluate the feasibility and safety of 18F-choline CLI to intraoperatively assess margin status in prostate cancer specimens and lymph node metastases. Methods: The PRIME study will recruit 30 patients with high-risk prostate cancer (defined as clinical stage >T2c, or PSA >20 ng/ml, or Gleason Score 8−10) undergoing radical robotic prostatectomy. Initial data from 3 patients are reported here. Patients received 370 MBq (±10%) of 18F-choline IV prior to surgery. Prostatectomy and lymph node excision specimens were imaged intra-operatively with an investigational CLI specimen analyser (Lightpoint Medical Ltd, UK) just after the excision (acquisition time 300 seconds, field-of-view 8 cm, matrix 512x512). The normalised decaycorrected radiance (ph/s/cm2/str/MBq) was calculated for each region of interest and the apparent tumour-to-background ratio (TBR) was reported. Radiation doses to staff were measured using badge dosimeters. Results: Intra-operative CLI images of 3 prostatectomy and 4 lymph node specimens were obtained. No time was added to surgery because of the CLI procedure and no other intra-operative issues were reported. Elevated radiance was observed in all the primary tumours with TBR 3.45, 4.90 and 2.49 respectively for each patient. No CLI signal was detected in the lymph nodes, which were also negatives on pathology reports. For 2 prostates with high-grade disease (Gleason 7), CLI analyses agreed with histological reports. For 1 prostate, CLI showed a basal signal whereas it was a low-grade apical prostate adenocarcinoma according to pathology. Basal signals, regarded as artefacts from the electro cautery device, were excluded from the analysis. Staff radiation doses mirrored the proximity to the patient and the duration of the procedure. To allow for radioactive decay (18-F half-life = 110 min), instruments were stored overnight before sterilisation and likewise pathology samples before transfer for analysis. Due to the robotic surgery, the assisting surgeon received the highest body dose followed by the scrub nurse (respectively 110–180 mSv and 40−80 mSv). Anaesthetic staff received <20 mSv and all other staff <10 mSv. Conclusions: Intra-operative 18 F-choline CLI is a feasible and low risk procedure. The CLI results from the first 3 patients show promise, and more data are needed to further evaluate this new intra-operative technique for measuring surgical margin and lymph node status. As CLI has a depth sensitivity of a few millimetres, further development is also required to restrict the signal to the surgical margin depths used in pathology. Conflict of interest: Ownership: Lightpoint Medical Limited. Advisory Board: Medical Advisory Board: Eli Avisar, MD − Mehra Golshan, MD − Henry Kuerer, MD, PhD, FACS − Malcolm Reed, MD. Scientific Advisory Board: Eric Aboagye, PhD − Sam Achilefu, PhD − James Basilion, PhD − Simon R. Cherry, PhD − Jan Grimm, MD, PhD. Board of Directors: David Tuch, PhD − CEO and Chairman of the Board. David Ford, MBA − NonExecutive Director. Martin Jamieson − Non-Executive Director. Elizabeth Usher, MBA − Non-Executive Director. William (Bill) Allan, MBA − NonExecutive Director. Ian Quirk − Executive Director. Corporate-sponsored Research: Yes. Other Substantive Relationships: the project was co-funded by Innovate UK. This project was a collaboration between University College Hospital of London and Lightpoint Medical Ltd. 2534 POSTER Concomitant use of emerging therapies and bone targeting agents in prostate cancer − observations from real-world data A. Liede1 , R. Hernandez2 , J. Lethen2 , D. Warner3 , A. Abernethy4 . 1 Amgen, Center for Observational Research, South San Fransicso, USA; 2 Amgen, Center for Observational Research, Thousand Oaks, USA; 3 Amgen, Global Development, Thousand Oaks, USA; 4 Flatiron Health, Medical Team, New York, USA Background: Clinical guidelines recommend emerging therapies and bone-targeting agents (BTAs) for the treatment and management of castration-resistant prostate cancer with evidence of bone metastases.

Abstracts However, it is unclear how to optimally sequence new therapies alongside BTAs to maximize effectiveness and safety. To address this gap, a first step is to examine current practice patterns using real world data. Material and Methods: A database of electronic medical records from >500K patients treated at >200 cancer centers across the United States, OSCER (Oncology Services Comprehensive Electronic Records, generated by Flatiron Health), was used to identify prostate cancer patients with bone metastases. Included were men treated with at least one emerging therapy (abiraterone acetate, cabazitaxel, enzalutamide, radium 223, sipuleucel-T) and a BTA (denosumab or zoledronic acid) between 1-Jan-2014 and 31-Dec-2014. Results: 1537 prostate cancer patients with bone metastases received an emerging therapy; of whom, 1224 (80%) received a BTA. Mean age was 74 years; during the study year, 22% received docetaxel (35% lifetime) and 54% received androgen deprivation therapy (57% lifetime). Patients received abiraterone acetate (56%), enzalutamide (47%), cabazitaxel (13%), sipuleucel-T (11%), and radium 223 (4%). More patients treated with emerging therapies received denosumab (68%) than zoledronic acid (39%). Patients received an average of 3.1 administrations or prescriptions of emerging therapies and 7.3 of BTAs during the study year. Table: Concomitant medications used from 1-Jan-2014 to 31-Dec-2014; patients may be in multiple categories

Any emerging therapy Same day Within two weeks Abiraterone acetate Cabazitaxel Enzalutamide Radium 223 Sipuleucel-T

N (%) Denosumab

Zoledronic acid

Any BTA

836 415 (50) 691 (83) 463 (55) 92 (11) 400 (48) 40 (5) 99 (12)

476 210 (44) 369 (78) 272 (57) 77 (16) 217 (46) 12 (3) 42 (9)

1224 614 (50) 1036 (85) 684 (56) 157 (13) 575 (47) 44 (4) 129 (11)

Conclusions: Real-world data suggests that practising oncologists are comfortable enough with co-administration of new prostate cancer treatments and BTAs that these drugs are used together in 4 out of 5 patients who are treated with an emerging therapy. Further follow up is needed to assess effectiveness and safety. Conflict of interest: Other Substantive Relationships: A. Liede, R. Hernandez, J. Lethen, and D. Warner are employees of and own stock in Amgen Inc. A. Abernethy is an employee of and owns stock in Flatiron Health. 2535 POSTER Clinical outcomes in chemotherapy-na¨ıve metastatic castrationresistant prostate cancer (mCRPC) patients (pts) treated with abiraterone acetate (ABI) stratified by prognosis ¨ 2 , B.J. Eigl1 , C. Kollmannsberger1 , C.M. Aviles1 , A.A. Azad1 , T. Todenhofer N. Murray1 , K. Chi1 . 1 BC Cancer Agency, Medical Oncology, Vancouver BC, Canada; 2 Vancouver Prostate Centre, Department of Urology, Vancouver BC, Canada Background: Pts with mCRPC can have very disparate outcomes. A prognostic index was developed from the COU-AA-301 trial in postchemotherapy mCRPC pts treated with ABI (J Clin Oncol 31, 2013 (suppl; abstr 5013)). The model included 6 risk-factors (RF) associated with poor outcome: ECOG performance status (PS) 2, presence of liver metastases, time from start of LHRH agonists/antagonists to start of ABI 36 months, albumin 40 g/L, alkaline phosphatase (ALP)  upper limit of normal (ULN) and lactate dehydrogenase (LDH) ULN. The aim of this study was to evaluate this model in an unselected, sequentially treated, population-based cohort of chemotherapy-na¨ıve mCRPC patients treated with ABI. Materials and Methods: We identified 246 chemotherapy-na¨ıve mCRPC patients treated with ABI between July 2009 and February 2015 at six British Columbia Cancer Agency centres. Patient records missing information on one of the six RFs were excluded. 197 patients were classified into good (0−1 RFs), intermediate (2−3 RFs) and poor (4−6 RFs) prognostic (prog) groups according to the COU-AA-301 model. PSA response rates (PSA decline 50% confirmed 3 weeks later), time to PSA progression (PCWG2 criteria) and OS data were collected. Univariate analysis examining association between baseline factors and survival outcomes was performed using Cox proportional hazards regression. Factors significant on univariate analysis were incorporated into a multivariate model for OS.

Abstracts

S487

Results: 31%, 52% and 17% of pts were classified as good, intermediate and poor risk respectively. PSA response, time to PSA progression and OS outcome significantly differed between prog group (Table). Compared to good prog pts, the HR (95% CI) for OS in intermediate and poor prog pts was 2.68 (1.60–4.47, p < 0.001; log-rank) and 6.53 (3.56–11.95, p < 0.001; log-rank). On multivariate analysis, ECOG PS (HR 2.5, p < 0.001), visceral metastases (HR 2.2, p = 0.03) and ALP (HR 2.2, p = 0.001) were confirmed as independent risk factors for decreased OS. Conclusion: The present analysis confirms that the prognostic index derived from the COU-301 study also prognostically discriminates chemotherapy-na¨ıve patients receiving ABI. Patients with intermediate and poor prognosis also had a lower PSA response rate and shorter time to progression. Identifying patients at risk of poor outcomes is important for informing clinical practice and clinical trial designs. Prognostic group

p-value

Good (0−1 RF)

Intermediate (2−3 RF)

Poor (4−6 RF)

38 6.6 13.8

39 5.6 8.7

PSA response [%] 55 Median time to PSA progression [months] 9.1 Median OS [months] 29.4

0.03* (chi-square) 0.04** (log-rank) <0.001** (log rank)

*Good vs. intermediate/poor prognosis patients. **Good vs. intermediate vs. poor prognosis patients.

No conflict of interest. 2536 POSTER Treatment sequence using new antiandrogens in castration resistant prostate cancer: A retrospective study S. Ohta1 , S. Hoshi2 , K. Numahata2 , M. Sasaki2 , T. Ookubo2 , H. Izumi3 , K. Ono3 , K.I. Oono1 , N. Yasuno4 , V. Bilim5 , K. Hoshi6 , H. Amemiya7 , I. Sasagawa6 . 1 Josai University, Faculty of Pharmaceutical Science, Sakado, Saitama, Japan; 2 Yamagata Prefectural Central Hospital, Urology, Yamagata, Japan; 3 Ishinomaki Redcross Hospital, Urology, Ishinomaki, Japan; 4 Kan-Etsu Hospital, Pharmacy, Tsurugashima, Japan; 5 Niigata Cancer Center, Urology, Niigata, Japan; 6 Yamagata Tokushukai Hospital, Urology, Yamagata, Japan; 7 Sakado Central Hospital, Urology, Sakado, Japan Background: Abiraterone acetate(AA) and enzalutamide(EZL) have been becoming available in Japan. Clinical trials demonstrated the benefit of these agents iin men with castration resistant prostate cancer(CRPC). The optimal sequencing of therapies in the context of efficacy and known crossresistance remains uncertain. Based on the mechanisms of action and clinical data, AA and EZL may be indicated in early stages of prostate cancer. Until clinical trials demonstrate the best treatment sequence, individualized therapy is required for each patient based on patient and disease characteristics. Material and Methods: We retrospectively analyzed 43 sequential patients (median age: 77(range 59−89), median serum PSA level: 56ng/ml (range 1.5–3211) with CRPC treated with EZL (160 mg qd) at our institution from June 2014 to November 2014. Twenty-one patients were pretreated with Docetaxel (DOC) and 22 patients were DOC-na¨ıve. Results: PSA after starting EZL was evaluated in 35 of 43 cases. Within 3 months after starting of treatment, declines in PSA by 30% or more was observed in 28 cases (80%). Eight patients (22%) pretreated with DOC and 3 (9%) DOC-na¨ıve patients demonstrated PSA increase. PSA reduction was observed in one case pretreated with DOC. In 3 DOC-na¨ıve cases PSA was unchanged. EZL dose was reduced in three cases, due to adverse events (body weight loss, fatigue and nausea). For the one case who had lost weight, the dose was gradually reduced, leading ultimately to complete discontinuation of EZL, but the decrease in PSA persisted for 3 months. This case could be explained with enzalutamide withdrawal syndrome (EWS), like an anti-androgen withdrawal syndrome. Conclusions: The efficacy of EZL was limited in AA pretreated patients after DOC administration. The cross-resistance to AA and EZL, EWS has been attributed to the expression of androgen receptor splice variant-7. Prospective studies are warranted to determine optimal treatment sequence in the new antiandrogens era. No conflict of interest.

2537 POSTER Preliminary findings from PLATO: A two-period, phase 4, randomized, double-blind, placebo-controlled study of continued enzalutamide treatment beyond progression in men with chemotherapy-na¨ıve metastatic castration-resistant prostate cancer (mCRPC) G. Attard1 , H. Gurney2 , Y. Loriot3 , M. Borre4 , C. Andresen5 , K. Wu6 , C. Taylor7 , A. Amelsberg8 , M.E. Taplin9 . 1 Institute of Cancer Research, Drug Development Unit, London, United Kingdom; 2 Westmead Hospital, Medical Oncology, Westmead, Australia; 3 Institut Gustave Roussy, Department of Cancer Medicine, Villejuif, France; 4 Aarhus University Hospital, Department of Clinical Epidemiology, Skejby, Denmark; 5 Medivation, Inc, Clinical Development, San Francisco, USA; 6 Medivation, Inc, Biostatistics, San Francisco, USA; 7 Astellas Pharma Global, Medical Affairs, Kingston upon Thames, United Kingdom; 8 Astellas Pharma, Medical Affairs Oncology, Northbrook, USA; 9 Dana-Farber Cancer Institute, Clinical Research, Boston, USA Background: Enzalutamide is an oral androgen receptor signalling inhibitor approved for the treatment of mCRPC. The primary objective of the ongoing PLATO trial (NCT01995513) is to determine the efficacy of combination treatment (Period 2) with continued enzalutamide (160 mg/day) plus abiraterone/prednisone (abi/P; daily 1000 mg/10 mg) vs placebo plus abi/P after prostate-specific antigen (PSA) progression on enzalutamide (Period 1). Methods: Men with chemotherapy-na¨ıve mCRPC were eligible. Only patients with PSA decline/stability relative to baseline at both Weeks 13 and 21 continue enzalutamide treatment in Period 1. Upon reaching confirmed PSA progression (25% increase in PSA and an absolute increase of 2 ng/mL above nadir), eligible patients are randomized to Period 2 (1:1 for continued enzalutamide plus abi/P or placebo plus abi/P). Randomization stratification is by Week 13 PSA response category. Results: 509 patients at 51 global sites were enrolled (November 2013 − September 2014). Median age was 72 years. Baseline median disease characteristics included: PSA 54 ng/mL; alkaline phosphatase 98 U/L; and lactate dehydrogenase 192 U/L. 163 patients (32%) had >10 bone metastases. As of December 2014, among 486 patients with Week 13 PSA data, 443 (91%) showed decline/stability relative to baseline; 393 (81%) and 189 (39%) had PSA declines 50% and 90%, respectively. Week 21 PSA results are not yet mature and 60 patients have been randomized into Period 2. The median time on enzalutamide during Period 1 (as of December 2014) was 5.6 months however 345 (68%) patients still remained on enzalutamide treatment. The most frequent grade 3 treatment-related adverse events included fatigue [1.4%], hypertension [0.8%] and nausea [0.6%]. No seizures have been reported. Conclusions: Preliminary findings on PSA responses and safety from Period 1 are consistent with prior studies of enzalutamide in mCRPC patients. The majority of patients (91%) had Week 13 PSA response data and continued Period 1 treatment. Period 1 (enzalutamide) and Period 2 (randomized phase) data continue to be collected. Conflict of interest: Advisory Board: Mary-Ellen Taplin: Medivation/ Astellas. Howard Gurney: Bayer, Jansen, Sanofi Aventis. Gert Attard: Roche/Ventana, Astellas, Janssen. Corporate-sponsored Research: Yohann Loriot: Sanofi. Other Substantive Relationships: Corina Andresen: Medivation employee. Catherine Taylor: Astellas employee. Kenneth Wu: Medivation employee. Andree Amelsberg: Astellas Employee. Yohann Loriot: Astellas, Sanofi, Bayer, Cellgene, Janssen, Oncogenex, Pierre Fabre. Gert Attard: Janssen-Cilag, Veridex, Roche/Ventana, Astellas, Medivation, Novartis, Millenium Pharma, Abbott Lab, Janssen, Takeda, Sanofi-Aventis, AstraZeneca, ICR. Mary-Ellen Taplin: Astellas/Medivation.