Prostate Cancer Working Group Research Articles

Abstract CT269: A phase 2 study of olaparib in combination with pembrolizumab in patients with previously treated advanced solid tumors with homologous recombination repair mutation (HRRm) and/or homologous recombination repair deficiency (HRD): KEYLYNK-007

Abstract Background: Treatment with the anti-PD-1 antibody pembrolizumab has improved clinical outcomes in multiple previously treated advanced solid tumors. The poly (ADP-ribose) polymerase (PARP) inhibitor olaparib has shown antitumor activity as monotherapy in patients with previously treated advanced ovarian, breast, pancreatic, and prostate cancers with BRCA1/BRCA2 mutations (BRCAm). Activity was also seen in patients with previously treated advanced solid tumors with other HRRm and in those with ovarian cancer with HRD phenotype. PARP inhibitors have been found to increase interferon signaling and tumor infiltrating lymphocytes, enhancing tumor susceptibility to immune checkpoint blockade. Antitumor activity of PD-(L)1 plus PARP inhibition was found to be higher than expected with either agent alone in patients with recurrent ovarian cancer regardless of BRCAm or HRD status and in patients with BRCAm breast cancer. KEYLYNK-007 (NCT04123366) evaluates the antitumor activity and safety of olaparib in combination with pembrolizumab in patients with previously treated advanced solid tumors with HRRm and/or HRD. Methods: This phase 2, nonrandomized, multicenter, open-label study plans to enroll approximately 300 patients aged ≥18 years with histologically/cytologically confirmed, previously treated, advanced solid tumors with HRRm and/or HRD per Lynparza HRR-HRD assay (Foundation Medicine, Inc., Cambridge, MA, USA), with an ECOG PS of 0-1. Patients will be grouped by biomarker status: subgroup 1: BRCAm; subgroup 2: HRRm without BRCAm; and subgroup 3: HRD positive without HRRm (loss of heterozygosity score ≥16 per Lynparza HRR-HRD assay). Patients will receive olaparib 300 mg twice daily + pembrolizumab 200 mg intravenously Q3W (35 cycles) until PD, unacceptable AEs, intercurrent illness, investigator decision, withdrawal of consent, or pregnancy. Tumor imaging assessment by blinded independent central review (BICR) per RECIST version 1.1 or Prostate Cancer Working Group (PCWG)-modified RECIST version 1.1 for prostate cancer will occur Q9W for 12 months, then Q12W until PD, start of new anticancer treatment, withdrawal of consent, pregnancy, or death. AEs will be monitored throughout the study and for 30 days after final dose (90 days for serious AEs) and are graded by National Cancer Institute Common Terminology Criteria for Adverse Events version 5. The primary endpoint is ORR (RECIST version 1.1 or PCWG-modified RECIST version 1.1 by BICR). Secondary endpoints include duration of response (DOR) and PFS (RECIST version 1.1 or PCWG-modified RECIST version 1.1 by BICR), OS, and safety. Point estimate and exact Clopper-Pearson CI for ORR, and Kaplan-Meier estimates for DOR, PFS, and OS will be calculated. Citation Format: Timothy A. Yap, Mallika Dhawan, Andrew E. Hendifar, Michele Maio, Taofeek K. Owonikoko, Miguel Quintela-Fandino, Ronnie Shapira-Frommer, Sanatan Saraf, Ping Qiu, Fan Jin, Alexander Gozman, Douglas A. Levine. A phase 2 study of olaparib in combination with pembrolizumab in patients with previously treated advanced solid tumors with homologous recombination repair mutation (HRRm) and/or homologous recombination repair deficiency (HRD): KEYLYNK-007 [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr CT269.

Evaluating biomarkers in metastatic castration-resistant prostate cancer patients treated with enzalutamide: PSA, circulating tumor cell counts, AR-V7 status and radiographic progression.

e17569 Background: Enzalutamideis ahighly effective treatment in metastatic castration resistant prostate cancer (mCRPC). Although Prostate Cancer Working Group (PCWG) guidelines recommend continuing treatment until radiographic/clinical progression (rPD/cPD), many patients discontinue therapy for rising PSA alone. Methods: We conducted an open label, randomized phase 2 trial in mCRPC patients untreated with docetaxel, abiraterone, or enzalutamide, comparing enzalutamide alone or in combination with PROSTVAC, a therapeutic cancer vaccine designed to induce an anti-tumor immune response. The study discontinued accrual after planned interim analysis indicated no difference in progression between the two arms. Patients were followed beyond 1st of 3 confirmed PSA rises until rPD. 49 patients were analyzed for Circulating Tumor Cell (CTC) count and AR-V7 status at 1st PSA rise and at rPD/cPD or last follow up. Results: 57 patients were enrolled with median follow up time of 55.4 mo. 49/57 (86%) patients had rising PSA; median time to 1st PSA rise for all patients was 6.4 mo (95% CI: 3.7-11.0 mo) after starting enzalutamide. 38/57 (67%) patients had progressive disease (majority with rPD; 1/38 (3%) with cPD); median time to progression for all patients was 23.3 mo (95% CI: 16.1-27.8 mo). 5 patients tested positive for AR-V7 within 30 days of rPD. In patients who experienced rPD/cPD, CTCs were detected in 11/24 (46%) samples taken at rPD vs. in only 3/24 (13%) samples taken at rising PSA. CTC counts were higher at rPD compared to samples taken at rising PSA (P = 0.004, Wilcoxon unpaired test). Of the 7 patients still being treated (median time on drug = 4.2 yrs), 2 experienced rising PSA; however none of the patients had detectable CTCs at a median of 30 days from last follow up. Conclusions: These data suggest that a rising PSA may not be a warning of near-term clinically significant disease progression in mCRPC patients treated with enzalutamide, given the 17-month difference between the first rise in PSA and ultimate rPD/cPD seen in this analysis. Further, CTCs and AR-V7 status associate strongly with rPD but not with rising PSA, adding biological rationale to the hypothesis that CTC counts and AR-V7 status are associated with disease progression. Collectively, these data highlight the need to continue to educate patients and providers on PCWG criteria for progression and appropriately-timed utilization of both therapies and diagnostic tests to maximize drug efficacy in mCRPC. Clinical trial information: NCT01867333 .

A phase II study of olaparib in combination with pembrolizumab in patients with previously treated advanced solid tumors with homologous recombination repair mutation (HRRm) and/or homologous recombination repair deficiency (HRD): KEYLYNK-007.

TPS3156 Background: The anti-PD-1 antibody pembrolizumab (pembro) has improved clinical outcomes in multiple previously treated advanced solid tumors. The poly (ADP-ribose) polymerase (PARP) inhibitor olaparib (ola) has shown antitumor activity as monotherapy in previously treated advanced cancers with BRCA1/ BRCA2 mutations (BRCAm), other HRRm, and ovarian cancer with HRD phenotype. Antitumor activity of PD-(L)1 plus PARP inhibition was reportedly higher than expected with either agent alone in patients (pts) with recurrent ovarian cancer regardless of BRCAm or HRD status and in pts with BRCAm breast cancer. KEYLYNK-007 (NCT04123366) evaluates antitumor activity and safety of ola plus pembro in pts with advanced solid tumors with HRRm and/or HRD. Methods: This phase 2, nonrandomized, multicenter, open-label study plans to enroll ~300 pts aged ≥18 y with histologically/cytologically confirmed, previously treated, advanced solid tumors with HRRm and/or HRD per Lynparza HRR-HRD assay (Foundation Medicine, Inc., Cambridge, MA, USA) and ECOG PS 0-1. Pts will be grouped by biomarker status: (1) BRCAm; (2) HRRm without BRCAm; (3) HRD positive without HRRm (loss of heterozygosity score ≥16 per Lynparza HRR-HRD assay). Pts will receive ola 300 mg BID + pembro 200 mg IV Q3W (35 cycles) until PD, unacceptable AEs, intercurrent illness, investigator decision, withdrawal, or pregnancy. Tumor imaging assessment by blinded independent central review (BICR) per RECIST v1.1 or Prostate Cancer Working Group (PCWG)-modified RECIST v1.1 for prostate cancer will occur Q9W for 12 mo, then Q12W until PD, start of new anticancer treatment, withdrawal, pregnancy, or death. AEs will be monitored throughout the study and for 30 days after final dose (90 days for serious AEs) and graded by NCI CTCAE v5. The primary endpoint is ORR (RECIST v1.1 or PCWG-modified RECIST v1.1 by BICR). Secondary endpoints include DOR, PFS (RECIST v1.1 or PCWG-modified RECIST v1.1 by BICR), OS, and safety. ORR will be analyzed by the Clopper-Pearson method; and DOR, PFS, and OS by the Kaplan-Meier method. Clinical trial information: NCT04123366 .

Age, Gleason Score, and PSA are important prognostic factors for survival in metastatic castration-resistant prostate cancer. Results of The Uroncor Group (Uro-Oncological Tumors) of the Spanish Society of Radiation Oncology (SEOR).

The treatment of metastatic castration-resistant prostate cancer (mCRPC) has changed significantly in recent years. Inhibitors of androgen receptors have shown especially significant benefits in overall (OS) and progression-free survival (PFS), with a good toxicity profile. Treatment selection depends on the patient's individual clinical, radiological, and biological characteristics. To describe treatment outcomes (efficacy, toxicity) in a cohort of patients with mCRPC in Spain. Multicenter, retrospective study of patients with mCRPC included in a database of the Urological Tumour Working Group (URONCOR) of the Spanish Society of Radiation Oncology (SEOR). Metastatic CRPC was defined according to the prostate cancer working group 3 (PCWG3) criteria. The Kaplan-Meier technique was used to evaluate OS and the Common Terminology Criteria for Adverse Events (CTCAE, v.4.0) were used to assess toxicity. Univariate and multivariate Cox regression analyses were performed to identify the factors significantly associated with OS. A total of 314 patients from 17 hospitals in Spain diagnosed with mCRPC between June 2010 and September 2017 were included in this study. Mean age at diagnosis was 68years (range 45-89). At a median follow-up of 35months, OS at 1, 3, and 5years were 92%, 38%, and 28%, respectively. Grades 1-2 and grade 3 toxicity rates were, respectively, 68% and 19%. No grade 4 toxicities were observed. On the multivariate analysis, the following factors were significantly associated with OS: age (hazard ratio [HR] 0.42, p = 0.010), PSA value at diagnosis of mCRPC (HR 0.55, p = 0.008), and Gleason score (HR 0.61, p = 0.009). Age, Gleason score, and PSA at diagnosis of mCRPC are independently associated with overall survival in patients with mCRPC. The efficacy and toxicity outcomes in this patient cohort treated in radiation oncology departments in Spain are consistent with previous reports.

The prostate cancer precision screening program: a preliminary report after recruitment of 2 159 men

Objective: The Chinese Anti-Cancer Association Genitourinary Cancer Committee Prostate Cancer Working Group released Consensus of prostate cancer (PCa) screening in 2017. This program aims to evaluate the methods and significance of prostate cancer precision screening in high risk population. Methods: A total of 2 159 eligible males enrolled from 13 community centers and 3 screening centers received PSA test from April 2017 to August 2018. Prostate-specific antigen (PSA) determination in serum with a cut-off of ≥4.0 ng/ml was the main screening test and indication for biopsy. The interviewer-administered questionnaire covered demographic characteristics and environmental exposure factors. The associations between these factors and prostate cancer risk were determined by multivariable unconditional logistic regression models. Results: Altogether, 271 cases (12.6%) had a confirmed PSA increase ≥ 4.0 μg/L (median 9.1, range 4.0-25.0). Subsequently, 57 subjects (21.0%) out of the 271 PSA-suspicious men underwent prostate biopsy, and 34 (59.6%) were confirmed as prostate cancer. Until now, the overall prostate cancer incidence in the first screening round was1.57%. There were no statistical differences in the distributions of PSA-suspicious and prostate cancer incidence between community centers and screening centers (P=0.578 and 0.735). Age (OR: 2.63; 95%CI: 1.84-3.75, P<0.001) and chronic prostatitis history (OR: 2.02; 95%CI: 1.55-2.63, P<0.001) were significantly associated with PSA level. After adjustment for these factors, older age (OR: 4.04; 95%CI: 1.71-9.59, P=0.002) and statins use (OR: 3.09; 95%CI: 1.25-7.69, P=0.015) were associated with an elevated risk of PCa. Conclusions: It is of substantial significance to screen prostate cancer in high risk population. Both community centers and screening centers methods are effective. Although largely underestimated, the incidence of PCa in the targeted Chinese population is higher than expected. Older men have a high risk of harboring PCa. Our study suggests a decreased risk of PCa in men with statins use. Prostate Cancer Precision Screening is promising to improve prostate cancer survival in China.

Prognostic importance of prostatic specific antigen response in patients who received Lutetium-177 prostate-specific membrane antigen treatment for castration resistant prostate cancer.

This study aims to analyze the prognostic importance of serum prostate specific antigen (PSA) response in patients who received radioligand therapy (RLT) with Lu-177 Prostate-specific membrane antigen (PSMA) for their castration-resistant prostate cancer. Thirty consecutive patients who received Lu-177 PSMA treatment for their castration-resistant prostate carcinoma were included. All the patients had undergone Ga-68 PSMA PET/CT scanning before Lu-177 PSMA therapy, which revealed multiple metastases. Patients were treated with a fixed dose (180 mCi) of Lu-177 PSMA at six to eight weeks intervals. PSA response was evaluated using Prostate Cancer Working Group 3 (PCWG3) criteria. Serum PSA response was classified as PSA progression (25% increase over the baseline and an increase in the absolute-value PSA level by at least 5 ng per millilitre), any <50% decline or ≥50% decline. PSA response was evaluated six weeks after every cycle. Response evaluation with radiological imaging and Ga-68 PSMA PET/CT were performed before the first cycle and eight weeks after the last cycle. Thirty patients were treated with a total of 171 cycles (median 4, range 3-7) of Lu-177 PSMA. A decline in serum PSA of ≥50% was detected in ten patients (33%) while a decline in PSA of any amount was observed in fifteen (50%) patients after the first cycle. After the last cycle, a decline in PSA ≥50% and of any amount was seen in thirteen (43%) and fourteen (46%) patients, respectively. Of the fifteen patients who were not responder after the first cycle, three (20%) had a decline in PSA of any amount after the completion of the RLT. Moreover, of the 20 patients who did not have a ≥50% decline in PSA level after the first cycle, four (20%) became responder after the last cycle. Regarding serum PSA response after the first cycle, median OS was significantly higher for patients who had ≥50% decline in PSA level with 21.0±10.0 (95% CI: 1.2-40.7) months compared to patients who had not with 8.0±2.6 (95% CI: 2.7-13.2) months (P=0.012). A decline in PSA of any amount after the first cycle did not have a significant impact on median OS (12.0±1.1 vs. 6.0±2.5 months, P=0.08). The decline in serum PSA level after the last cycle of treatment had a significant impact on OS. Median OS for the decline in PSA of any amount was calculated as 13.0±1.0 (95% CI: 10.9-15.0) months for responders and 6.0±1.9 (95% CI: 2.2-9.7) months for non-responders (P=0.016). Considering ≥50% of decline as a response, median OS was 21.0±5.8 (95% CI: 9.5-32.4) months for responders and 6.0±3.0 (95% CI: 0.1-11.8) months for non-responders (P=0.026). Serum PSA level during RLT with Lu-177 PSMA remains a clinically significant factor to predict OS times. About twenty percent of patients who were not responder after the first cycle could become responder after the last cycle. However, patients without PSA response after completion of all cycles should be closely followed-up. Non-responder patients can achieve a response with further treatments.

171TiP - Phase II study of olaparib in previously treated advanced solid tumours with homologous recombination repair mutation (HRRm) or homologous recombination repair deficiency (HRD): LYNK-002

BackgroundPoly(ADP-ribose) polymerases (PARPs) play a key role in DNA damage repair (DDR). DDR defects due to HRRm (eg BRCA mutation [BRCAm]) or resulting in HRD (eg global loss of heterozygosity) may sensitize tumors to PARP inhibitors, eg olaparib. Olaparib monotherapy has activity in BRCAm ovarian, breast, pancreatic, and prostate cancer, and in prostate cancer with DDR defects beyond BRCAm (TOPARP). Olaparib improved efficacy outcomes vs placebo/chemotherapy as treatment in≤3rd-line (3L) HER2-negative BRCAm breast cancer (OlympiAD) and ≥2L BRCAm ovarian cancer (SOLO3), and maintenance therapy in≥1L ovarian cancer irrespective of BRCAm (SOLO1, Study 19). LYNK-002 (NCT03742895) evaluates HRRm/HRD positivity (HRD+; per Lynparza HRR-HRD assay, Foundation Medicine, Inc., Cambridge, MA) as biomarkers of tumor-agnostic response to olaparib. Trial designThis open-label, phase 2 study will enroll ∼370 patients (pts) ≥18 y with previously treated, histologically/cytologically confirmed HRRm/HRD+(per Lynparza HRR-HRD assay) advanced solid tumors who failed/are intolerant to/ineligible for available SOC and have no PD during prior platinum-based treatment (any number of prior regimens), measurable disease per RECIST v1.1/Prostate Cancer Working Group (PCWG)-modified RECIST v1.1, no CNS metastases, ECOG PS 0–1, and no persistent toxicity from prior therapy. Newly obtained/archival tumor samples will be centrally evaluated using the Lynparza HRR-HRD assay to confirm eligibility. Pts will be grouped into 2 cohorts: 1) solid tumors with BRCAm (n∼84; excluding breast and ovarian), 2) solid tumors with HRRm (BRCA non-mutated; n∼174)/HRD (n∼112) per Lynparza HRR-HRD assay. Pts will receive olaparib 300mg BID until documented PD/unacceptable toxicity/study withdrawal. Tumor imaging will occur at baseline, Q8W for 1 y, and then Q12W per RECIST v1.1 by BICR/PCWG-modified RECIST v1.1 (modified for ≤5 target lesions/organ; 10 total). Primary endpoint is ORR. Key secondary endpoints are DOR, PFS, and OS. AEs will be graded using NCI CTCAE v4.0. Enrollment is ongoing at 51 sites in 15 countries. As of Apr 18, 2019, 23 patients have been enrolled. Clinical trial identificationNCT03742895. Editorial acknowledgementCindy Taylor, PhD, of C4 MedSolutions, LLC (Yardley, PA, USA), a CHC Group company, funded by Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc., Kenilworth, NJ, USA, and AstraZeneca. Legal entity responsible for the studyMerck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc., Kenilworth, NJ, USA, and AstraZeneca. FundingMerck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc., Kenilworth, NJ, USA, and AstraZeneca. DisclosureD. Hyman: Travel / Accommodation / Expenses, Personal fees: Atara Biotherapeutics; Travel / Accommodation / Expenses, Personal fees: Chugai Pharma; Travel / Accommodation / Expenses, Personal fees: CytomX Therapeutics; Travel / Accommodation / Expenses, Personal fees: Boehringer Ingelheim; Travel / Accommodation / Expenses, Personal fees: AstraZeneca; Research grant / Funding (institution), Research funding: Puma Biotechnology; Research grant / Funding (institution), Research funding: AstraZeneca; Research grant / Funding (institution), Research funding: Loxo Oncology. A. Hendifar: Advisory / Consultancy: Novartis; Advisory / Consultancy: Ipsen; Advisory / Consultancy: Perthera. H. Cheol Chung: Research grant / Funding (institution): Lilly; Research grant / Funding (institution): GSK; Research grant / Funding (institution): MSD; Research grant / Funding (institution): Merck-Serono; Research grant / Funding (institution): BMS/Ono; Research grant / Funding (institution): Taiho; Honoraria (institution): Merck-Sorono; Honoraria (institution): Lilly/Foundation Medicine; Advisory / Consultancy: Taiho; Advisory / Consultancy: Celltrion; Advisory / Consultancy: MSD; Advisory / Consultancy: Lilly; Advisory / Consultancy: Quintiles; Advisory / Consultancy: BMS; Advisory / Consultancy: Merck-Serono. M. Maio: Advisory / Consultancy: Bristol-Myers Squibb; Advisory / Consultancy: Merck Sharp & Dohme; Advisory / Consultancy: Incyte; Advisory / Consultancy: AstraZeneca; Advisory / Consultancy: Glaxo SmithKline; Advisory / Consultancy: Merck Serono; Advisory / Consultancy: Roche. A. Leary: Advisory / Consultancy, Advisory board: Tesaro; Advisory / Consultancy, Advisory board: AstraZeneca; Advisory / Consultancy, Advisory board: Clovis; Advisory / Consultancy, Advisory board: GamaMabs; Advisory / Consultancy, Advisory board: Gridstone; Advisory / Consultancy, Advisory board: Seattle Genetics; Research grant / Funding (institution), Research funding from the lab: Merus; Research grant / Funding (institution), Research funding from the lab: Inivata; Research grant / Funding (institution), Research funding from the lab: GamaMabs. J. Rhee: Full / Part-time employment: AstraZeneca Pharmaceuticals LP. M. Marton: Full / Part-time employment: employee of Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc., Kenilworth, NJ, USA. M. Chen: Full / Part-time employment: employee of Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc., Kenilworth, NJ, USA. S. Krishnan: Full / Part-time employment: Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc., Kenilworth, NJ, USA. R. Shapira: Speaker Bureau / Expert testimony, Speaker honoraria: MSD; Speaker Bureau / Expert testimony, Speaker honoraria: BMS; Speaker Bureau / Expert testimony, Speaker honoraria: Roche; Speaker Bureau / Expert testimony, Speaker honoraria: Novartis; Speaker Bureau / Expert testimony, Speaker honoraria: AstraZeneca. All other authors have declared no conflicts of interest.

Abstract CT229: Olaparib in patients (pts) with previously treated, homologous recombination repair mutation (HRRm) or homologous recombination deficiency (HRD)-positive advanced cancer: Phase II LYNK-002 study

Abstract Background: Human cancers are associated with defects in DNA damage repair (DDR). Evidence suggests a key role for poly(ADP-ribose) polymerases (PARPs) in repairing certain DNA damage lesions. Olaparib (a PARP inhibitor) is approved for pts with germline BRCA1 and BRCA2-mutated breast and ovarian cancers, and pts with or without BRCA mutation in recurrent ovarian cancer. Mutations in HRR genes (HRRm; beyond BRCA1 or BRCA2) and HRD may sensitize tumors to respond to PARP inhibitors. Olaparib has also shown favorable ORRs in HRRm/HRD-positive (HRD+) cancers, including prostate and ovarian. Thus, this study (NCT03742895) aims to evaluate the use of HRRm/HRD+ as biomarkers of tumor-agnostic response to olaparib monotherapy. Methods: Eligibility for this open-label, Phase II study requires pts ≥18 years of age with a previously treated, histologically/cytologically confirmed, HRRm/HRD+ advanced solid tumor; who have failed, are intolerant to, or ineligible for all available standard of care therapies; with no disease progression during prior platinum-based treatment. At baseline, pts should also have measurable disease per RECIST v1.1 or Prostate Cancer Working Group (PCWG)-modified RECIST v1.1 (for pts with prostate cancer) without CNS metastases, ECOG PS of 0 or 1, and no persistent toxicities (CTCAE grade &amp;gt;2) from prior cancer therapy. Pts may have received any number of prior regimens. Newly obtained or archival tumor samples will be centrally evaluated using the Lynparza HRR Assay (under development at Foundation Medicine, Inc). Pts will be grouped into 2 cohorts: cohort 1 will include pts with any solid tumor type with a BRCA1 or BRCA2 mutation (excluding breast and ovarian cancers); cohort 2 will include pts whose tumor (any type) is BRCA1 or BRCA2 wild-type and HRRm and/or HRD+ as determined by loss of heterozygosity score. Pts will receive olaparib 300 mg orally BID until documented disease progression, unacceptable toxicity, or study withdrawal. Tumor imaging will be performed at baseline, with response assessments Q8W in the first year and Q12W thereafter, per RECIST v1.1 by BICR or PCWG-modified RECIST v1.1, both modified to follow ≤5 target lesions per organ (10 total). AEs will be graded using NCI CTCAE v4.0. The primary endpoint is ORR; the point estimate and 95% CI calculated using the Clopper-Pearson method will be provided. Summary statistics for key secondary efficacy endpoints of duration of response, OS, and PFS will be provided using the Kaplan-Meier method. Safety endpoints will be summarized. Approximately 370 pts will be enrolled (~84 in cohort 1 [BRCA1 and BRCA2 mutated]; ~174 HRRm and ~112 HRD+ in cohort 2 [BRCA1 and BRCA2 wild-type]). Enrollment is ongoing in 5 countries beginning December 12, 2018. Citation Format: David Hyman, Andrew Hendifar, Hyun Cheol Chung, Michele Maio, Alexandra Leary, Iben Spanggaard, Joon Rhee, Matt Marton, Menghui Chen, Suba Krishnan, Ronnie Shapira. Olaparib in patients (pts) with previously treated, homologous recombination repair mutation (HRRm) or homologous recombination deficiency (HRD)-positive advanced cancer: Phase II LYNK-002 study [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr CT229.

Circulating tumor DNA fraction (ctDNA) as a surrogate predictive biomarker in metastatic castration-resistant prostate cancer (mCRPC).

5039 Background: Plasma ctDNA is a promising minimally invasive biomarker in mCRPC. Pre-treatment high levels of ctDNA reflect poor prognosis (Romanel et al, Sci Transl Med 2015; Annala et al, Cancer Discov 2018). However, the role of plasma ctDNA in prostate tumour monitoring is largely unexplored. We aimed to determine if monitoring tumour response by quantifying ctDNA levels in plasma could enable early assessment of therapy efficacy for mCRPC. Methods: Between January 2011 and June 2016, 132 sequential plasma samples from 54 mCRPC patients (pts) (30 pre- and 24 post-chemotherapy) treated with abiraterone (abi) were collected. Targeted next-generation sequencing was performed on the PGM Ion Torrent using a 316 or 318 Chip to account for 1000X expected coverage per target. We estimated the global tumour content for each sequential plasma sample from study patients by using the approach developed in (Carreira et al, Sci Trasl Med 2014; Romanel et al, Sci Transl Med 2015 ), which extends the CLONET framework (Prandi et al, Genome Biol 2014). Prostate Cancer Working Group -3 (PCWG3) criteria were used to assess clinical, biochemical (PSA) and radiographic (RAD) progression disease (PD). We considered ctDNA PD any increase of ctDNA from baseline value. Results: In our cohort of 54 pts (median age: 75 years, range 70-78), we observed 17 (31.5%) PD, 14 (25.9%) stable disease, and 23 (42.6%) partial/complete response after the first 3 months (mo) abi therapy. The odds ratio (OR) for PD having any increase in ctDNA and a PSA decline &lt; 50% at ~3-mo therapy was 10.83, 95% CI 2.55-45.95, P = 0.001, and 3.27, 95% CI 0.89-12.3, P = 0.074, respectively. In addition, we assessed all 3 types of median PD time from starting abi treatment, suggesting the ability of ctDNA variation to predict overall PD [RAD PD = 6.8 mo, PSA PD = 4.4 mo, and ctDNA PD = 3.0 mo, P = 0.008). An increase of ctDNA levels during the first 3-mo abi treatment was significantly associated with a long-term androgen deprivation therapy (ADT) before plasma sample collection (previous ADT &gt; 24 mo vs 12 &gt; previous ADT ≤23 mo vs &lt; 12 mo: P = 0.036). Conclusions: In mCRPC, an early change in ctDNA fraction may be considered as a predictive biomarker playing a key role in individualized disease monitoring. Prospective evaluation of treatment decisions based on ctDNA is now required.

JAVELIN BRCA/ATM: A phase 2 trial of avelumab (anti–PD-L1) plus talazoparib (PARP inhibitor) in patients with advanced solid tumors with a BRCA1/2 or ATM defect.

TPS2660 Background: Defects in DNA damage response genes, including BRCA1/2 and ATM, confer sensitivity to PARP inhibitors. Talazoparib is a potent, oral PARP inhibitor with a dual mechanism of action (PARP enzyme inhibition and PARP trapping). Avelumab is a human anti–PD-L1 IgG1 monoclonal antibody with a wild-type Fc region that has shown clinical activity in multiple tumor types. Preclinical and early clinical data suggest that combining a PARP inhibitor with an immune checkpoint inhibitor may provide improved activity. Methods: JAVELIN BRCA/ATM (NCT03565991) is an ongoing, open-label, multicenter, phase 2 trial assessing the combination of avelumab and talazoparib. Enrollment of ≈200 patients with a histologically confirmed locally advanced or metastatic solid tumor that has progressed on &gt; 1 line of standard-of-care treatment for locally advanced or metastatic disease and has a germline or somatic defect in BRCA1 or 2 (cohort 1) or ATM (cohort 2) genes is planned. Patients with concomitant defects in &gt; 1 gene ( BRCA1, BRCA2, or ATM) will be enrolled in cohort 1. Exclusion criteria include prior treatment with an immune checkpoint or PARP inhibitor, prior treatment with any other anticancer or radiation therapy within 2 weeks prior to enrollment, a known history of an immune-mediated or autoimmune condition, and known symptomatic brain metastases requiring steroids. The primary endpoint is confirmed objective response by blinded independent central review according to RECIST v1.1 and according to the Prostate Cancer Working Group 3 (PCWG3) for patients with metastatic castration-resistant prostate cancer (mCRPC). Secondary endpoints include safety; investigator-assessed confirmed objective response, time to tumor response, duration of response, and progression-free survival (per RECIST v1.1 and per PCWG3 for patients with mCRPC); overall survival; pharmacokinetic parameters; and potential predictive biomarkers. The study is currently enrolling patients at centers in the United States and Europe. Clinical trial information: NCT03565991.

Phase II trial of carfilzomib for metastatic castration-resistant prostate cancer (mCRPC) following androgen pathway inhibitors.

224 Background: mCRPC is an incurable disease with suboptimal outcomes following prior therapy. Bortezomib, a proteasome inhibitor, has exhibited activity in a subset of patients. Carfilzomib is a second-generation selective and irreversible proteasome inhibitor and is approved for refractory myeloma. Methods: A non-randomized phase II trial (NCT02047253) was designed to evaluate carfilzomib for mCRPC following abiraterone acetate (AA) and/or enzalutamide (enza); prior docetaxel (D) was allowed. A 6-month progression-free survival (PFS) rate ≥30% defined by Prostate Cancer Working Group (PCWG) guidelines was considered important, while PFS &lt; 10% was not. History and physical exam, and prostate specific antigen (PSA) was performed every 4 weeks. Circulating tumor cells (CTCs) were measured at baseline and 12 weeks later. Radiographic evaluation was performed every 12 weeks. Carfilzomib was administered on days 1,2,8,9,15,16 every 28 days. The starting dose was 20 mg/m2 during the first week followed by dose escalation to 56 mg/m2 if no serious toxicities occurred. Daily oral acyclovir was administered for herpes zoster prophylaxis. Therapy continue until PCWG or symptomatic progression or severe toxicities. Results: Twenty-eight patients were recruited and prior AA, enza or D had been received by 21 pts each and 20 pts received &gt; 1 of these agents. The median age was 70 (range 55-88). One patient attained 6-month PFS; 2 other patients progressed at 6 months. Minor PSA declines and CTC declines were observed in 3 patients each, and one patient exhibited both PSA and CTC declines. The major toxicities of any grade were: anemia (n = 13, 46%), Fatigue (n = 7, 25%), and Constipation (n = 5, 18%), with anorexia, cough, fever, headache and thrombocytopenia in 4 patients each (14%). The major toxicities of grade ≥3 in &gt; 1 patient were: anemia (n = 3, 11%) and hypertension (n = 2, 7%). Conclusions: Carfilzomib is not active as salvage therapy following AA and/or enza in unselected patients with mCRPC. Minor and transient activity may be present in a small subset of patients. Clinical trial information: NCT02047253.

Prospective comparative study of 18F-sodium fluoride PET/CT and planar bone scintigraphy for treatment response assessment of bone metastases in patients with prostate cancer

Aim: To compare 18F-sodium fluoride positron emission tomography/computed tomography (NaF PET/CT) and 99mTc-labelled diphosphonate bone scan (BS) for the monitoring of bone metastases in patients with prostate cancer undergoing anti-cancer treatment.Material and methods: Data from 64 patients with prostate cancer were included. The patients received androgen-deprivation therapy (ADT), next-generation hormonal therapy (NGH) or chemotherapy. The patients had a baseline scan and 1–3 subsequent scans during six months of treatment. Images were evaluated by experienced nuclear medicine physicians and classified for progressive disease (PD) or non-PD according to the Prostate Cancer Working Group 2 (PCWG-2) criteria. The patients were also classified as having PD/non-PD according to the clinical and prostate-specific antigen (PSA) responses.Results: There was no difference between NaF PET/CT and BS in the detection of PD and non-PD during treatment (McNemar’s test, p = .18). The agreement between BS and NaF PET/CT for PD/non-PD was moderate (Cohen’s kappa 0.53, 95% confidence interval 0.26–0.79). Crude agreement between BS and NaF PET/CT for the assessment of PD/non-PD was 86% (89% for ADT, n = 28; 88% for NGH, n = 16, and 80% for chemotherapy, n = 20). In most discordant cases, BS found PD when NaF PET/CT did not, or BS detected PD on an earlier scan than NaF PET/CT. Biochemical progression (27%) occurred more frequently than progression on functional imaging (BS, 22% and NaF PET/CT, 14%). Clinical progression was rare (11%), and almost exclusively seen in patients receiving chemotherapy.Conclusion: There was no difference between NaF PET/CT and BS in the detection of PD and non-PD; however, BS seemingly detects PD by the PCWG-2 criteria earlier than NaF-PET, which might be explained by the fact that NaF-PET is more sensitive at the baseline scan.

Abstract LB-058: ABIraterone (ABI) and ENZalutamide (ENZ) induce changes in immunologic profile of patients with metastatic castration-resistant prostate cancer (mCRPC)

Abstract Background: ABIraterone (ABI) is a CYP17-lyase inhibitor, while ENZalutimide (ENZ) is an androgen receptor (AR) antagonist that inhibits nuclear translocation. Changes in serum cytokines have been noted in patients (pts) receiving docetaxel for metastatic castration-resistant prostate cancer (mCPRC) therapy (Mahon KL et al Br J Cancer 2015). We postulate that ABI and ENZ may also have a complex effect on cytokine profile. Methods: In a prospective trial in mCPRC pts, ABI or ENZ was given according to physician preference. Blood was drawn at baseline, 4 weeks, 8 weeks, 12 weeks and at the time of progressive disease (PD). Plasma was separated from patients’ blood using Vacutainer CPT tubes (BD) within 2 hours after collection by centrifuging at 1800×g for 20 min at room temperature and stored in -80°c. Plasma samples were analyzed for 30 human cytokines and chemokines using Luminex FLEXMAP 3D system. Trends in serum cytokine profile were analyzed by supervised clustering, with segregation based on radiographic progression-free survival (rPFS) according to Prostate Cancer Working Group 3 (PCWG3) criteria. Results: From May 2013 to June 2016, 33 pts were enrolled with a median age of 67. 13 and 20 pts received ABI and ENZ, respectively. Of these, 13 pts had received prior treatment with the opposing agent (e.g., ABI→ENZ, or ENZ→ABI). Prior docetaxel was rendered in 4 pts. 16 pts had rPFS &amp;lt; 6 mos, while 17 pts had rPFS ≥ 6 mos. Using supervised clustering, higher levels of GM-CSF (P=0.008) and IL-10 (P=0.008) were noted at 8 weeks in pts with rPFS ≥ 6 mos, while lower levels of IL-17 (P=0.008) and VEGF (P=0.001) were observed in this cohort. Across the entire cohort, a trend was noted with sequential decline in HGF from baseline to 4 and 8 weeks, but a pronounced rise was observed at the time of progression (P&amp;lt;0.05 for comparison of progression to baseline and 4 weeks). Conclusions: Our study suggests HGF as a mediator of ABI/ENZ resistance, supporting the well-established role of the HGF/MET signaling axis in prostate cancer pathogenesis. After initiation of therapy, lower levels of proinflammatory and proangiogenic mediators such as IL-17 and VEGF, respectively, are associated with protracted response to ABI and ENZ. These results may inform combination trials in mCRPC incorporating checkpoint inhibitors or other immune modulators. Note: This abstract was not presented at the meeting. Citation Format: Meghan Salgia, Marc L. Perez, Jeremy Jones, Hae Jung Won, Valeriy Poroyko, Przemyslaw Twardowski, Marcin Kortylewski, Sumanta K. Pal. ABIraterone (ABI) and ENZalutamide (ENZ) induce changes in immunologic profile of patients with metastatic castration-resistant prostate cancer (mCRPC) [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr LB-058. doi:10.1158/1538-7445.AM2017-LB-058

177Lu-PSMA-617 radioligand therapy and outcome in patients with metastasized castration-resistant prostate cancer.

Radioligand therapies targeting prostate-specific membrane antigen (PSMA) have been established for the treatment of metastasized castration-resistant prostate cancer (mCRPC) in the last decade and show promising response rates and a favourable toxicity profile. The aim of this study was to evaluate the overall survival (OS) and to identify parameters predicting outcome in mCRPC patients treated with 177Lu-PSMA-617. Between December 2014 and January 2017, 59 consecutive patients (median age 72years; interquartile range, (IQR, 66-76years) with mCRPC, who had been treated with at least one next-generation antihormonal drug as well as chemotherapy, were included in this study. Biochemical response was evaluated using Prostate Cancer Working Group 3 (PCWG3) criteria. Survival was evaluated using Kaplan-Meier estimates and Cox regression proportional hazards model. Toxicity was assessed using Common Toxicity Criteria for Adverse Events (CTCAE). The study was approved by the local ethics committee. The 59 patients were treated with a total of 159cycles (median 3cycles, range 1-7) of 177Lu-PSMA-617 (median dose 6.11GBq, IQR 5.9-6.3GBq). The median follow-up was 24weeks (IQR 15-36weeks). Follow-up data for at least 12weeks (PCWG3) were available in 76% (45) of the patients. For outcome results data from all patients treated with at least one cycle were analysed. A decline in prostate-specific antigen (PSA) of ≥50% occurred in 53%, and a decline in PSA of any amount in 91% of patients. The estimated median OS was 32weeks. An initial alkaline phosphatase (ALP) level <220U/L and a PSA decline after the first cycle were associated with a longer OS (56 vs. 28weeks, p<0.01, and 56 vs. 29weeks, p=0.04, respectively). The median estimated PSA progression-free survival (PPFS) was 18weeks. Only ALP level <220U/L was significantly associated with a longer PPFS (41 vs. 18weeks, p<0.01). A PSA decline after the first cycle of 177Lu-PSMA-617 and an initial ALP level <220U/L were predictors of a longer OS in patients with end-stage mCRPC. An ALP level <220U/L was additionally associated with a longer PPFS.

Translating prostate cancer working group (PCWG) criteria into a quantitative progression biomarker in metastatic castration resistant prostate cancer (mCRPC).

5068 Background: mCRPC is a bone dominant lethal disease. A validated endpoint in mCRPC trials is bone scan progression, which is semi-quantitative and rely on the appearance of new lesions as proposed by the PCWG. The validated automated bone scan index (BSI) quantifies the bone tumor burden as the fraction of total skeletal weight. To build on the current definition of disease progression, we sought to compare the association of time to progression with overall survival (OS) using PCWG criteria and BSI increase. Methods: mCRPC patients (pts) enrolled on trials of agents targeting androgen-receptor (AR) were assessed. Pts were required to have a raw bone scan image for BSI analysis concurrent with disease assessments. The EXINI automated computing platform generated the BSI values. Thresholds for the absolute and relative increase in BSI from 1st follow-up (≤12 weeks) were explored for the time to BSI progression. The association with survival time was computed for each threshold defined time to BSI progression. Kendall’s Tau, derived from the Clayton copula, was used to associate time to BSI progression with survival time, where both endpoints may be censored. Results: A total of 257 pts were assessed, of whom 169 had raw bone scans images needed for the BSI analysis. 90 pts (53%) met progression by PCWG criteria, the association between the time to PCWG progression and OS was 0.52. The association between time to BSI progression and OS was comparable to the PCWG progression when the absolute increase in BSI was 0.6 or more (table below). Conclusions: Progression in bone can be expressed as a single quantitative metric that describes the increase in total disease burden while retaining the same association that PCWG has with OS. These data represent the first steps to a quantitative expression of bone disease progression as a clinical trials endpoint. [Table: see text]

Consensus of prostate cancer screening

The incidence of prostate cancer is increasing rapidly in China, the clinical stage of prostate cancer patients is comparatively late and the overall survival rate is inferior to that reported in the developed countries. Prostate cancer screening is an effective measure to reduce the risk of death through early detection. In order to identify the best way of prostate cancer screening in China, the Chinese Anti-Cancer Association Genitourinary Cancer Committee Prostate Cancer Working Group reviewed all published data concerning the benefits and harms of screening for prostate caner and created the consensus. The consensus include the following points: screening asymptomatic men for prostate cancer by prostate specific antigen(PSA)testing in the general population is the potential measure to reduce mortality rates through early detection, PSA testing should be offered earlier in men with life expectancy over 10 years and men at high risk of prostate cancer.

Phase Ib dose-finding study of abiraterone acetate plus buparlisib (BKM120) or dactolisib (BEZ235) in patients with castration-resistant prostate cancer

BackgroundThe phosphatidylinositol-3-kinase (PI3K)/protein kinase B (Akt) signalling axis and androgen receptor (AR) pathways exhibit reciprocal feedback regulation in phosphatase and tensin homologue (PTEN)-deficient metastatic castration-resistant prostate cancer (CRPC) in preclinical models. This phase Ib study evaluated the pan-PI3K inhibitor buparlisib (BKM120) and the dual pan-PI3K/ mammalian target of rapamycin (mTOR) inhibitor dactolisib (BEZ235) in combination with abiraterone acetate (AA) in patients with CRPC. Materials and methodsPatients with CRPC who had progressed on AA therapy received escalating doses of either buparlisib or dactolisib, along with fixed doses of AA (1000 mg once daily (qd)) and prednisone (5 mg twice daily (bid)). The primary objective was to define the maximum tolerated dose (MTD) and/or the recommended dose for expansion (RDE) of either buparlisib or dactolisib in combination with AA. Secondary objectives included safety, antitumour activity (Prostate Cancer Working Group 2 (PCWG2) criteria; 30% of prostate-specific antigen (PSA) decline at ≥week 12) and pharmacokinetic (PK) profile. ResultsIn buparlisib + AA arm, 25 patients received buparlisib + AA (median age, 67 years; Eastern Cooperative Oncology Group performance status (ECOG PS) of 0/1/2 for 7/17/1 patients, respectively). At 100 mg qd; two patients experienced dose-limiting toxicities (DLTs) (grade 3 hyperglycaemia; grade 2 asthenia), and this was the maximum buparlisib dose explored. Buparlisib + AA showed a 26% lower median area under the curve from time zero to 24°h (AUC0–24) and 48% lower median maximum serum concentration (Cmax) versus the single-agent buparlisib assessed in first-in-human study. No objective response and few PSA decreases were reported.In dactolisib + AA arm, 18 patients (median age, 71 years; ECOG PS of 0/1 for 6/12 patients, respectively) received dactolisib + AA at the first dose level (200 mg bid). Five patients had 9 DLTs (grades 2&3 stomatitis; grade 3 hyperglycaemia; grades 2& 3 diarrhoea; grades 1& 2 pyrexia, grade 2 vomiting, and grade 2 chills). ConclusionsBased on the assessment of available pharmacokinetics, safety, and efficacy data, no further study is planned for either buparlisib or dactolisib in combination with AA in CRPC.

Observer agreement of treatment responses on planar bone scintigraphy in prostate cancer patients: importance of the lesion assessment method.

The aim of this study was to assess observer agreement on the evaluation of treatment responses of bone metastases by bone scintigraphy (BS) using different scoring methods in prostate cancer patients. Sixty-three paired BS from 55 patients were included. BS was performed before and after more than 12 weeks of anticancer treatment. A panel of experienced nuclear medicine physicians from several institutions evaluated treatment response using three different methods: (a) standard clinical assessment, (b) MD Anderson criteria, and (c) Prostate Cancer Working Group 2 (PCWG-2) criteria. All methods were based on the evaluation of paired before-after bone scans. Readers were able to classify the presence of bone metastases at baseline with a high level of agreement [Cohen's κ=0.94, 95% confidence interval (CI) 0.82-1.00]. Observer agreement on bone response by PCWG-2 criteria showed considerable agreement (Cohen's κ=0.84, 95% CI: 0.69-0.99). Evaluation using standard clinical assessment and MD Anderson criteria showed moderate agreement (0.52, 95% CI: 0.36-0.69 and 0.64, 95% CI: 0.48-0.79, respectively). There was considerable variation among readers for regional lesion count on individual scans, with limits of agreement of -10 to 10 lesions or more for the majority of anatomical regions, including the thorax, spine, and pelvis. Observer agreement on treatment response by BS varied notably across methods. Optimal agreement was achieved by the PCWG-2 criteria. Variation in the classification of treatment response of bone metastases may have a significant impact on clinical decision-making, emphasizing the need for a uniform approach, including during clinical practice. Response assessment by lesion counting on repeated BS without access to previous scans cannot be recommended.

Translating Prostate Cancer Working Group 2 (PCWG2) progression criteria into a quantitative response biomarker in metastatic castration-resistant prostate cancer (mCRPC).

170 Background: PCWG2 radiographic progression criteria, which are associated with survival, rely on lesion counting. There is a need for a fully quantitative assessment of tumor burden as a component of a true response biomarker for mCRPC. Here, we used the bone scan index (BSI) to fully quantitate the increase in skeletal disease burden at each radiographic milestone that constitutes the PCWG2 criteria. Methods: mCRPC patients (pts) from clinical trials using PCWG2 criteria to determine progression (PD) were assessed. Pts were required to have baseline (BL) and at least two follow-up (FU) bone scans. The EXINI automated platform was used to generate BSI at key PCWG2 landmarks: 2+2 criteria for early PD and post flare PD criteria with the appearance of 1 and ≥2 new lesions. Median (M) and Interquartile range (IQR) of the relative change in BSI were calculated to quantify the increase in total tumor burden. Results: A total of 257 pts were assessed, of whom 169 had two or more FU bone scans at 8 or 12 week intervals. Of the total 169 pts, 86 (51%, 95%CI 43-58) met PD by PCWG criteria. 35 (41%, 95%CI 31-51) of 86 pts met the early PD criteria, the remaining 51 (59%, 95%CI 49-69) met PD at subsequent time points after flare period. The ability of the automated platform to reproduce a BSI value, retrieved from the same scan, was highly consistent (100%). The relative BSI increase during the course of meeting PD by PCWG2 is shown in the Table. Conclusions: This is the first quantitative assessment of changes in total tumor burden in pts meeting PCWG2 criteria. Relative changes in BSI can be substantial in meeting the criteria. These data build on the PCWG2 criteria by quantitating the increase both of existing lesions and the contribution of new lesions. We are now assessing the associations with survival that these incremental increases represent. [Table: see text]

Integration of bone scan (BS) and computerized tomography (CT) findings as an endpoint to assess bone metastasis in metastatic castration-resistant prostate cancer (mCRPC).

191 Background: Progression of bone metastasis in mCRPC is assessed solely by BS findings and correlates modestly with overall survival (OS). Given the lack of reliability of BS findings and the ready availability of routinely performed CT scans, which commonly identify bone metastases, we aimed to better assess progression in bone by integrating BS and CT findings and to explore their association with OS. Methods: Data were obtained from patients treated at the University of Utah receiving docetaxel-based chemotherapy (D) or post-docetaxel therapy with orteronel (O). Patients with both baseline and on-therapy CT and BS within 90 days were eligible for analysis. CT and BS underwent central radiology review for bone lesions by a single radiologist. Progressive disease (PD) was defined as ≥ 1 new lesion. Survival was measured from start of therapy. Cox proportional hazards regression was used to explore potential prognosticators of overall survival (OS). Statistical significance was defined as 2-sided p &lt; 0.05. Therapy was a stratification factor. Results: Twenty-eight patients were evaluable including 18 patients receiving D, and 10 receiving O post-docetaxel. The mean age of these patients was 71.4 years and median (95% CI) overall survival was 18.4 (9.7-35.4) months. Four patients had PD on both BS and CT, while 2 (7%) had PD on CT but not BS and 3 had PD on BS but not CT. Patients with PD on BS or CT had worse OS (HR = 2.68, 95% CI = 1.04-6.90, p = 0.041) than those with no PD on either CT or BS. Looking at individual lesions, 4 (14%) patients had new lesions identified on CT which was not observed using BS, and they were associated with worse OS (HR = 3.72, 1.01-13.66, p = 0.048). Conversely, no significant difference in OS was observed for 4 patients with lesions identified on BS which were not observed using CT (HR = 2.67, 0.58-12.32, p = 0.21). Conclusions: This hypothesis-generating study suggests that CT can complement and enhance the ability of BS to capture PD and predict OS. Integration of BS findings using Prostate Cancer Working Group (PCWG)-3 guidelines to define PD and CT bone findings should be investigated in a larger study as an intermediate endpoint.