• Decreased fracture rate by mandating bone-protecting agents in the EORTC 1333/PEACE III trial comparing enzalutamide and Ra223 versus enzalutamide alone: an interim safety analysis

      Tombal, BF; Loriot, Y; Saad, F; McDermott, RS; Elliott, Tony; Rodriguez-Vida, A; Nole, F; Fournier, B; Collette, L; Gillessen, Silke; et al. (2019)
    • Disease characteristics and completion of treatment in patients with metastatic castration-resistant prostate cancer treated with radium-223 in an international early access program

      Saad, F; Gillessen, Silke; Heinrich, D; Keizman, D; O'Sullivan, J; Nilsson, S; Miller, K; Wirth, M; Reeves, J; Seger, M; et al. (2019)
      BACKGROUND: Radium-223 is approved by the US Food and Drug Administration and European Medicines Agency for the treatment of metastatic castration-resistant prostate cancer (mCRPC). There are currently no markers for selecting patients most likely to complete radium-223 treatment. PATIENTS AND METHODS: In this phase IIIb, international, single-arm study, patients received radium-223, 55 kBq/kg, every 4 weeks for </=6 cycleS Primary end points were safety and overall survivaL In post hoc analyses patients were grouped according to number of radium-223 injections received (1-4 or 5-6). Associations between baseline covariates and number of injections were investigated. RESULTS: Of 696 eligible patients, 473 (68%) had received 5 to 6 radium-223 injections and 223 (32%) 1 to 4 injectionS Patients with less pain (moderate-severe vS none-mild, odds ratio [OR], 0.41; P < .0001), lower Eastern Cooperative Oncol.ogy Group performance status (>/=2 vS 0-1, OR, 0.51; P = .0074), lower prostate-specific antigen level (>141 mug/L vS </=141 mug/L, OR, 0.40; P < .0001), and higher hemoglobin level (<10 g/dL vS >/=10 g/dL, OR, 0.50; P = .0206) were more likely to receive 5 to 6 than 1 to 4 injectionS Median overall survival was not reached and was 6.3 months (95% confidence interval, 5.4-7.4) in patients who had received 5 to 6 and 1 to 4 radium-223 injections, respectivelY Adverse events were less common in patients who received 5 to 6 than 1 to 4 injections; anemia was reported in 87 (18%) and 64 (29%) patients, respectively. CONCLUSION: Patients with less advanced mCRPC are more likely to receive 5 to 6 radium-223 injections and to achieve better overall survivaL Consideration of baseline and disease characteristics is recommended before initiation of radium-223 treatment.
    • Health-related quality of life (HRQoL) in patients with metastatic castration-resistant prostate cancer (mCRPC) treated with olaparib in combination with abiraterone

      Clarke, Noel W; Thiery-Vuillemin, A; Wiechno, PJ; Alekseev, B; Sala, N; Jones, R; Kocak, I; Chiuri, VE; Jassem, J; Flechon, A; et al. (2019)
    • Intermittent androgen suppression for rising PSA level after radiotherapy.

      Crook, J; O'Callaghan, C; Duncan, G; Dearnaley, D; Higano, C; Horwitz, E; Frymire, E; Malone, S; Chin, J; Nabid, A; et al. (2012-09-06)
      Intermittent androgen deprivation for prostate-specific antigen (PSA) elevation after radiotherapy may improve quality of life and delay hormone resistance. We assessed overall survival with intermittent versus continuous androgen deprivation in a noninferiority randomized trial.
    • Management of patients with advanced prostate cancer: report of the Advanced Prostate Cancer Consensus Conference 2019

      Gillessen, Silke; Attard, G; Beer, TM; Beltran, H; Bjartell, A; Bossi, A; Briganti, A; Bristow, Robert G; Chi, KN; Clarke, Noel W; et al. (2020)
      BACKGROUND: Innovations in treatments, imaging, and molecular characterisation in advanced prostate cancer have improved outcomes, but there are still many aspects of management that lack high-level evidence to inform clinical practice. The Advanced Prostate Cancer Consensus Conference (APCCC) 2019 addressed some of these topics to supplement guidelines that are based on level 1 evidence. OBJECTIVE: To present the results from the APCCC 2019. DESIGN, SETTING, AND PARTICIPANTS: Similar to prior conferences, experts identified 10 important areas of controversy regarding the management of advanced prostate cancer: locally advanced disease, biochemical recurrence after local therapy, treating the primary tumour in the metastatic setting, metastatic hormone-sensitive/naïve prostate cancer, nonmetastatic castration-resistant prostate cancer, metastatic castration-resistant prostate cancer, bone health and bone metastases, molecular characterisation of tissue and blood, inter- and intrapatient heterogeneity, and adverse effects of hormonal therapy and their management. A panel of 72 international prostate cancer experts developed the programme and the consensus questions. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: The panel voted publicly but anonymously on 123 predefined questions, which were developed by both voting and nonvoting panel members prior to the conference following a modified Delphi process. RESULTS AND LIMITATIONS: Panellists voted based on their opinions rather than a standard literature review or formal meta-analysis. The answer options for the consensus questions had varying degrees of support by the panel, as reflected in this article and the detailed voting results reported in the Supplementary material. CONCLUSIONS: These voting results from a panel of prostate cancer experts can help clinicians and patients navigate controversial areas of advanced prostate management for which high-level evidence is sparse. However, diagnostic and treatment decisions should always be individualised based on patient-specific factors, such as disease extent and location, prior lines of therapy, comorbidities, and treatment preferences, together with current and emerging clinical evidence and logistic and economic constraints. Clinical trial enrolment for men with advanced prostate cancer should be strongly encouraged. Importantly, APCCC 2019 once again identified important questions that merit assessment in specifically designed trials. PATIENT SUMMARY: The Advanced Prostate Cancer Consensus Conference provides a forum to discuss and debate current diagnostic and treatment options for patients with advanced prostate cancer. The conference, which has been held three times since 2015, aims to share the knowledge of world experts in prostate cancer management with health care providers worldwide. At the end of the conference, an expert panel discusses and votes on predefined consensus questions that target the most clinically relevant areas of advanced prostate cancer treatment. The results of the voting provide a practical guide to help clinicians discuss therapeutic options with patients as part of shared and multidisciplinary decision making.
    • Management of patients with advanced prostate cancer: the report of the advanced prostate cancer consensus conference APCCC 2017.

      Gillessen, S; Attard, G; Beer, T; Beltran, H; Bossi, A; Bristow, R; Carver, B; Castellano, D; Chung, B; Clarke, Noel W; et al. (2017-06-24)
      In advanced prostate cancer (APC), successful drug development as well as advances in imaging and molecular characterisation have resulted in multiple areas where there is lack of evidence or low level of evidence. The Advanced Prostate Cancer Consensus Conference (APCCC) 2017 addressed some of these topics.
    • Multimodal detection of homologous recombination repair gene mutations (HRRm) in a phase II trial of olaparib plus abiraterone in metastatic castrate resistant prostate cancer (mCRPC)

      Carr, TH; Adelman, C; Barnicle, A; Kozarewa, I; Luke, S; Lai, Z; Menon, S; Hollis, S; Dougherty, B; Harrington, EA; et al. (2018)
    • Olaparib combined with abiraterone in patients with metastatic castration-resistant prostate cancer: a randomised, double-blind, placebo-controlled, phase 2 trial.

      Clarke, Noel W; Wiechno, P; Alekseev, B; Sala, N; Jones, R; Kocak, I; Chiuri, V; Jassem, J; Fléchon, A; Redfern, C; et al. (2018-06-04)
      Patients with metastatic castration-resistant prostate cancer and homologous recombination repair (HRR) mutations have a better response to treatment with the poly(ADP-ribose) polymerase inhibitor olaparib than patients without HRR mutations. Preclinical data suggest synergy between olaparib and androgen pathway inhibitors. We aimed to assess the efficacy of olaparib plus the androgen pathway inhibitor abiraterone in patients with metastatic castration-resistant prostate cancer regardless of HRR mutation status.
    • Patients (pt) characteristics and treatment patterns in the radium (Ra)-223 REASSURE observational study.

      Higano, C; Zimberg, S; Dizdarevic, S; Harshman, L; Logue, John P; Baldari, S; Richardson, T; Bottomley, D; Tombal, B; Sade, J; et al. (2018)
    • Radium-223 in asymptomatic patients with castration-resistant prostate cancer and bone metastases treated in an international early access program

      Heidenreich, A; Gillessen, Silke; Heinrich, D; Keizman, D; O'Sullivan J; Carles, J; Wirth, M; Miller, K; Reeves, J; Seger, M; et al. (2019)
      Radium-223, a targeted alpha therapy, is used to treat symptomatic patients with castration-resistant prostate cancer (CRPC) and bone metastases. Data for radium-223 in asymptomatic CRPC patients with bone metastases are lacking. METHODS: This was a prospective, single-arm phase 3b study. Patients with metastatic CRPC (malignant lymphadenopathy not exceeding 6?cm was allowed, visceral disease was excluded) received radium-223, 55?kBq/kg intravenously, every 4?weeks for up to 6?cycles. Co-primary endpoints were safety and overall survival. Post hoc analyses were performed according to baseline asymptomatic or symptomatic disease status. Asymptomatic status was defined as no pain and no opioid use at baseline. RESULTS: Seven hundred eight patients received ?1 radium-223 injection: 548 (77%) were symptomatic to various degrees, and 135 (19%) were asymptomatic. Asymptomatic patients had more favorable baseline disease characteristics than symptomatic. A lower proportion of asymptomatic versus symptomatic patients had received prior abiraterone (25% vs 35%) and prior docetaxel (52% vs 62%). A higher proportion of asymptomatic (71%) versus symptomatic (55%) patients completed radium-223 treatment. Overall survival (hazard ratio [HR] 0.486), time to disease progression (HR 0.722) and time to first symptomatic skeletal event (HR 0.328) were better in asymptomatic than symptomatic patients. Alkaline phosphatase (ALP) response rates were similar (46% vs 47%), and ALP normalization (44% vs 25%) and prostate-specific antigen response rates (21% vs 13%) were higher in asymptomatic than symptomatic patients. A lower proportion of asymptomatic patients reported treatment-emergent adverse events (TEAEs, 61% vs 79%), grade 3-4 TEAEs (29% vs 40%) and drug-related TEAEs (28% vs 44%). There were two treatment-related deaths, both in patients with baseline symptomatic disease. CONCLUSIONS: Using radium-223 earlier in the disease course, when patients are asymptomatic or minimally symptomatic, may enable patients to complete treatment and optimize treatment outcome compared to symptomatic patients, and therefore may allow sequencing with other life-prolonging therapies. TRIAL REGISTRATION: The study was registered with ClinicalTrials.gov , number NCT01618370 on June 13, 2012 and the European Union Clinical Trials Register, EudraCT number 2012-000075-16 on April 4, 2012.
    • Timing of radiotherapy (RT) after radical prostatectomy (RP): First results from the RADICALS RT randomised controlled trial (RCT) [NCT00541047]

      Parker, C; Clarke, Noel W; Cook, A; Kynaston, HG; Petersen, PM; Cross, W; Persad, R; Catton, C; Logue, John P; Payne, H; et al. (2019)