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Community Practice Connections™: Personalized Sequencing in Castration-Resistant Prostate Cancer: Bridging the Latest Evidence to the Bedside in Clinical Management PER Pulse™ Recap

PER Pulse Recap

PER Pulse™ Recap

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PER Pulse™ Recap

Clinical Considerations for Patients with Hormone-Sensitive, Metastatic Prostate Cancer

The treatment paradigm for patients with metastatic prostate cancer continues to evolve, with several recent studies providing new information regarding options for patients with hormone-sensitive prostate cancer, as well as those who have castration-resistant prostate cancer (CRPC). Androgen-deprivation therapy (ADT) has been a historical cornerstone of treatment for patients with hormone-sensitive, metastatic prostate cancer, a group that accounts for approximately 3% of new prostate cancer diagnoses.1-3 One key STAMPEDE phase III study compared long-term hormone therapy (standard of care [SOC]) versus SOC plus zoledronic acid versus SOC plus docetaxel versus SOC, zoledronic acid, and docetaxel.5 Median survival with the combination of docetaxel and ADT was 81 months compared with 71 months with ADT alone, leading to the incorporation of docetaxel into the SOC for appropriate patients who are hormone treatment‒naïve.4,5

The recent phase III, randomized, controlled CHAARTED trial3 assessed the addition of docetaxel to standard ADT for the treatment of patients with metastatic ADT-naïve disease. This study showed that the combination of ADT plus docetaxel was associated with improved outcomes compared with ADT alone (median overall survival OS [OS], median time to clinical progression, and development of metastatic castration-resistant prostate cancer [mCRPC]).3 The phase III LATITUDE trial1 has also recently assessed the efficacy of abiraterone acetate plus prednisone with ADT versus ADT plus placebo in patients with newly diagnosed metastatic prostate cancer, showing benefits with respect to OS and radiographic progression-free survival (rPFS).1 Furthermore, significant improvements were seen in the group treated with abiraterone with respect to multiple other outcomes, including time until pain progression, prostate-specific antigen (PSA) progression, symptomatic skeletal-related events (SREs), initiation of chemotherapy, and subsequent prostate cancer therapy1

Dr Beer provides his perspectives on recent advancements in the treatment of patients with metastatic castration-sensitive prostate cancer. With respect to the role of chemotherapy in metastatic castration-sensitive prostate cancer, large randomized trials have shown an improvement in OS with the addition of 6 cycles of docetaxel to ADT. When available, subset analyses (including those that are prospectively stratified) have shown evidence of benefit in patients with more-extensive disease, particularly those with de novo metastatic disease. The benefit of chemotherapy in nonmetastatic disease remains to be established, as does the benefit of chemotherapy in patients with low-volume metastatic disease.


  1. Fizazi K, Tran N, Fein L, et al. Abiraterone plus prednisone in metastatic, castration-sensitive prostate cancer [published online June 4, 2017]. N Engl J Med. 2017. doi: 10.1056/NEJMoa1704174.
  2. Weiner AB, Matulewicz RS, Eggener SE, Schaeffer EM. Increasing incidence of metastatic prostate cancer in the United States (2004-2013). Prostate Cancer Prostatic Dis. 2016;19(4):395-397. doi: 10.1038/pcan.2016.30.
  3. Sweeney CJ, Chen Y-H, Carducci M, et al. Chemohormonal therapy in metastatic hormone-sensitive prostate cancer. N Engl J Med. 2015;373(8):737-746. doi: 10.1056/NEJMoa1503747.
  4. James ND, de Bono JS, Spears MR, et al. Abiraterone for prostate cancer not previously treated with hormone therapy [published online June 3, 2017]. N Engl J Med. 2017. doi: 10.1056/NEJMoa1702900.
  5. James ND, Sydes MR, Clarke NW, et al. Addition of docetaxel, zoledronic acid, or both to first-line long-term hormone therapy in prostate cancer (STAMPEDE): survival results from an adaptive, multiarm, multistage, platform randomised controlled trial. Lancet. 2016;387:1163-1177. doi: 10.1016/S0140-6736(15)01037-5.

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PER Pulse™ Recap

Management Approaches for Patients with Early Metastatic CRPC

When selecting an agent for first-line therapy for a patient with metastatic castration-resistant prostate cancer , several factors need to be considered. Disease-related factors include symptoms that the patient is experiencing, performance status , sites of metastases, duration of prior androgen-deprivation therapy , as well as other prior treatment regimens. Patient-related factors include age, comorbidities, toxicity concerns, cost concerns, and patient preference for options, such as route of medication administration. There are several treatment options which are reviewed for patients with castration-resistant prostate cancer , including sipuleucel-T, abiraterone, enzalutamide, radium-223, and chemotherapy. Several recent studies such as ALSYMPCA, PREVAIL, and IMPACT have helped to shed light on safety and efficacy of these therapies, as well as other factors which may influence treatment selection.1-12 Dr Sonpavde provides his perspectives on different treatment options, sequencing considerations, and treatment-related toxicity management for these patients.


  1. Kantoff PW, Higano CS, Shore ND, et al. Sipuleucel-T immunotherapy for castration-resistant prostate cancer. N Engl J Med. 2010;363(5):411-422. doi: 10.1056/NEJMoa1001294.
  2. National Comprehensive Cancer Network. NCCN Clinical Practice Guidelines in Oncology: Prostate Cancer. Version 2.2017. Accessed July 6, 2017.
  3. Schellhammer PF, Chodak G, Whitmore JB, Sims R, Frohlich MW, Kantoff PW. . Lower baseline prostate-specific antigen is associated with a greater overall survival benefit from sipuleucel-T in the Immunotherapy for Prostate Adenocarcinoma Treatment (IMPACT) trial. Urology. 2013;81(6):1297-1302. doi: 10.1016/j.urology.2013.01.061.
  4. Ryan CJ, Smith MR, Fizazi K, et al. Abiraterone acetate plus prednisone versus placebo plus prednisone in chemotherapy-naïve men with metastatic castration-resistant prostate cancer (COU-AA-302): final overall survival analysis of a randomised, double-blind, placebo-controlled phase 3 study. Lancet Oncol. 2015;16(2):152-160. doi: 10.1016/S1470-2045(14)71205-7.
  5. Beer TM, Armstrong AJ, Rathkopf DE, et al. Enzalutamide in metastatic prostate cancer before chemotherapy. N Engl J Med. 2014;371(5):424-433. doi: 10.1056/NEJMoa1405095.
  6. Beer TM, Armstrong AJ, Rathkopf D, et al. Enzalutamide in men with chemotherapy-naïve metastatic castration-resistant prostate cancer: extended analysis of the phase 3 PREVAIL study. Eur Urol. 2017;71(2):151-154. doi: 10.1016/j.eururo.2016.07.032.
  7. Parker C, Nilsson S, Heinrich D, et al. Alpha emitter radium-223 and survival in metastatic prostate cancer. N Engl J Med. 2013;369(3):213-223. doi: 10.1056/NEJMoa1213755.
  8. Berthold DR, Pond GR, Soban F, de Wit R, Eisenberger M, Tannock IF. . Docetaxel plus prednisone or mitoxantrone plus prednisone for advanced prostate cancer: updated survival in the TAX 327 study. J Clin Oncol. 2008;26(2):242-245. doi: 10.1200/JCO.2007.12.4008.
  9. Lavaud P, Gravis G, Legoupil C, et al. How should we treat castration-resistant prostate cancer patients who have received androgen deprivation therapy (ADT) plus docetaxel upfront for hormone-sensitive disease? Mature analysis of the GETUG-AFU 15 phase III trial. Ann Oncol. 2016;27(6):243-265. doi: 10.1093/annonc/mdw372.
  10. Sartor AO, Oudard S, Sengelov L, et al. Cabazitaxel vs docetaxel in chemotherapy-naïve patients with metastatic castration-resistant prostate cancer: a three-arm phase III study (FIRSTANA). Presented at: the 2016 American Society of Clinical Oncology Annual Meeting; June 3-7, 2016; Chicago, IL. Abstract 5006. doi: 10.1200/JCO.2016.34.15_suppl.5006.
  11. Sonpavde G, Huang A, Wang L, Baser O, Miao R. First-line chemotherapy versus anti-androgen therapy for patients with metastatic castration-resistant prostate cancer (mCRPC): individual patient analysis of the Veterans Health Administration (VHA) dataset. Presented at: the 2017 American Society of Clinical Oncology Annual Meeting; June 2-6, 2017; Chicago, IL. Abstract 156. doi: 10.1200/JCO.2017.35.6_suppl.156.
  12. Terada N, Maughan BL, Akamatsu S, et al. Exploring the optimal sequence of abiraterone and enzalutamide in patients with chemotherapy-naïve castration resistant prostate cancer: the Kyoto-Baltimore collaboration. Int J Urol. 2017;24(6):441-448. doi: 10.1111/iju.13346.

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PER Pulse™ Recap

Optimizing Treatment for Patients with Metastatic CRPC

When considering treatment options for patients with metastatic castration-resistant prostate cancer (mCRPC), it is important to consider not only site of metastases, but also symptoms that the patient is experiencing when selecting treatment options. Control of pain is important for all patients, particularly those with bony metastases. Palliative radiotherapy (RT) may be appropriate for bony metastases associated with prostate cancer1,2; single lesions may be managed with external-beam RT (EBRT). According to therapeutic guidelines from the American College of Radiology, most patients should be treated with a single course of 8 Gy for metastases that are not vertebral.3 However, patients with diffuse disease are candidates for systemic therapy.

Several treatments have been approved to control pain or have specific indications for patients who are symptomatic, including radiopharmaceuticals, the combination of mitoxantrone plus prednisone, samarium-153, and radium-223 (for patients whose symptoms arise from bone metastases). Beta-emitters, such as samarium-153 and strontium-89, are commonly used for painful bony metastases, but these do not improve survival.1 Radium-223 has been shown to prolong overall survival (OS), as well as time to first symptomatic skeletal-related event (SRE). In the phase III ALSYMPCA study,2 the median OS and median time to first symptomatic SRE were significantly greater for patients who received radium 223 compared to those treated with placebo. Abiraterone and enzalutamide have also been studied in the treatment of patients with CRPC who have symptomatic bony metastases,3,4 and Dr Scher provides his perspectives on data that have helped to govern his treatment selections for these patients. He also discusses treatment monitoring and other factors that may help to optimize patient outcomes.

Approximately 25% of patients with mCRPC have visceral metastases. Many treatment options have been studied in this patient population, and Dr Higano discusses the evidence from key studies such as PREVAIL and AFFIRM.5,6 Liver and lung metastases should be considered separately. In both the PREVAIL and AFFIRM studies, patients with liver metastases had a much worse prognosis, whereas the OS in patients with lung metastases was similar to those who had only bone metastases.5,6 The presence of visceral metastases is associated with poor survival, but does not necessarily mean that the patient will not be likely to respond to therapy.7 Furthermore, the prevalence of visceral disease in these patients increases over time, and often there is a discordance between prostate-specific antigen and radiological progression of visceral disease.7 When visceral metastases are identified, biopsy may help to determine histological and molecular characterization of tumors and guide treatment selection, as there is sometimes discordance between archival and fresh tissue.7 Tumor heterogeneity further contributes to the complexity of analysis and treatment decisions.


  1. National Comprehensive Cancer Network. NCCN Clinical Practice Guidelines in Oncology: Prostate Cancer. Version 2.2017. Accessed July 6, 2017.
  2. Parker C, Nilsson S, Heinrich D, et al. Alpha emitter radium-223 and survival in metastatic prostate cancer. N Engl J Med. 2013;369(3):213-223. doi: 0.1056/NEJMoa1213755.
  3. Logothetis CJ, Basch E, Molina A, et al. Effect of abiraterone acetate and prednisone compared with placebo and prednisone on pain control and skeletal-related events in patients with metastatic castration-resistant prostate cancer: exploratory analysis of data from the COU-AA-301 randomised trial. Lancet Oncol. 2012;13(12):1210-1217. doi: 10.1016/S1470-2045(12)70473-4.
  4. Fizazi K, Scher HI, Miller K, et al. Effect of enzalutamide on time to first skeletal-related event, pain, and quality of life in men with castration-resistant prostate cancer: results from the randomised, phase 3 AFFIRM trial. Lancet Oncol. 2014;15(10):1147-1156. doi: 10.1016/S1470-2045(14)70303-1.
  5. Alumkal JJ, Chowdhury S, Loriot Y, et al. Effect of visceral disease site on outcomes in patients with metastatic castration-resistant prostate cancer treated with enzalutamide in the PREVAIL trial [published online March 3, 2017]. Clin Genitourin Cancer. 2017. pii: S1558-7673(17)30050-2. doi: 10.1016/j.clgc.2017.02.007.
  7. Loriot Y, Fizazi K, de Bono JS, Forer D, Hirmand M, Scher HIl. Enzalutamide in castration-resistant prostate cancer patients with visceral disease in the liver and/or lung: outcomes from the randomized controlled phase 3 AFFIRM trial. Cancer. 2017;123(2):253-262. doi: 10.1002/cncr.30336.
  8. Pezaro C, Omlin A, Lorente D, et al. Visceral disease in castration-resistant prostate cancer. Eur Urol. 2014;65(2):270-273. doi: 10.1016/j.eururo.2013.10.055.

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