Advertisement

Drugs

, Volume 79, Issue 4, pp 381–400 | Cite as

The Evolving Systemic Treatment Landscape for Patients with Advanced Prostate Cancer

  • Martina Pagliuca
  • Carlo Buonerba
  • Karim Fizazi
  • Giuseppe Di LorenzoEmail author
Review Article

Abstract

Prostate cancer (PC) is a major health issue in developed countries, with, on the one hand, men suffering from sequelae related to unnecessary treatment of non-lethal PC, and, on the other hand, still dying because of advanced PC that progresses to castration-resistant disease. Systemic treatment is the mainstay of therapy of castration-resistant PC (CRPC). To date, a multitude of systemic agents have been tested and many of these have failed to provide a clinically meaningful benefit in CRPC, while others have been approved by the US Food and Drug Administration and/or the European Medicines Agency, including antiandrogen hormonal drugs (abiraterone, enzalutamide, apalutamide), chemotherapy (docetaxel and cabazitaxel), immunotherapy (Sipuleucel-T), and radiopharmaceutical (Radium-223) agents. In this review, systemic treatments regarded as most likely to have an impact in clinical practice are presented and discussed. In addition to the pivotal clinical studies, selected retrospective and non-randomized clinical trials are also discussed if deemed to have an impact on clinical practice or future research. A comprehensive appraisal of the expanding landscape of systemic therapies for advanced PC is provided from an expert perspective, with a focus on novel classification and diagnostic tools that have been paving the way for the development of precision medicine in PC.

Notes

Compliance with Ethical Standards

Funding

No external funding was used in the preparation of this manuscript.

Conflict of Interest

Dr. Pagliuca has no discloses to declare. Dr. Buonerba reports receiving research grants to his institution from Sanofi, Astellas, Quercegen Pharmaceuticals, and AstraZeneca; and consulting and travel expenses from Sanofi. Prof. Fizazi reports receiving consulting fees or honorarium from AstraZeneca, Janssen, Astellas, Sanofi, Orion, CureVac, Novartis, Bayer, and Amgen; support for travel to meetings for the study, manuscript preparation, or other purposes from Amgen and Janssen; and payment for lectures, including service on speakers’ bureaus, from Janssen. Dr. Di Lorenzo reports receiving research grants to his institution from Sanofi, Astellas, Quercegen Pharmaceuticals, and AstraZeneca; and consulting fees and travel expenses from Sanofi.

References

  1. 1.
    Siegel RL, Miller KD, Jemal A. Cancer statistics, 2017. CA Cancer J Clin. 2017;67:7–30.CrossRefGoogle Scholar
  2. 2.
    Stratton K, Cookson M. Castration-resistant prostate cancer: an algorithmic approach. Urol Clin N Am. 2017;44:647–55.CrossRefGoogle Scholar
  3. 3.
    Parker CC, James ND, Brawley CD, Clarke NW, Hoyle AP, Ali A, et al. Articles radiotherapy to the primary tumour for newly diagnosed, metastatic prostate cancer (STAMPEDE): a randomised controlled phase 3 trial. Lancet. 2018;6736:1–14.Google Scholar
  4. 4.
    Leyh-Bannurah SR, Gazdovich S, Budäus L, Zaffuto E, Briganti A, Abdollah F, et al. Local therapy improves survival in metastatic prostate cancer. Eur Urol. 2017;72:118–24.CrossRefPubMedGoogle Scholar
  5. 5.
    Miller RE, Dudderidge T, Huddart R, Seckl MJ, Rustin GJ, Christmas TJ. Re: pathological findings after primary chemotherapy in patients undergoing simultaneous orchidectomy and retroperitoneal lymph node dissection for advanced germ cell tumours. J Urol. 2013;190(6):2096.CrossRefGoogle Scholar
  6. 6.
    Rescigno P, Buonerba C, Bellmunt J, Sonpavde G, De Placido S, Di Lorenzo G. New perspectives in the therapy of castration resistant prostate cancer. Curr Drug Targets. 2012;13:1676–86.CrossRefPubMedGoogle Scholar
  7. 7.
    Di Lorenzo G, Buonerba C, Autorino R, De Placido S, Sternberg CN. Castration-resistant prostate cancer: current and emerging treatment strategies. Drugs. 2010;70(8):983–1000.CrossRefPubMedGoogle Scholar
  8. 8.
    Nuhn P, De Bono JS, Fizazi K, Freedland SJ, Grilli M, Kantoff PW, et al. Update on systemic prostate cancer therapies: management of metastatic castration-resistant prostate cancer in the era of precision oncology. Eur Urol. 2019;75(1):88–99.CrossRefPubMedGoogle Scholar
  9. 9.
    Buonerba C, Di Lorenzo G. The Sooner, the better: the establishment of a treatment paradigm in prostate cancer. Front Pharmacol. 2017;8:788.CrossRefPubMedPubMedCentralGoogle Scholar
  10. 10.
    Di Lorenzo G, Buonerba C. Oligometastatic prostate cancer: is it only a matter of perspective? Eur Urol. 2018.  https://doi.org/10.1016/j.eururo.2018.12.010 (Epub 24 Dec 2018).CrossRefPubMedGoogle Scholar
  11. 11.
    Tosoian JJ, Gorin MA, Ross AE, Pienta KJ, Tran PT, Schaeffer EM. Oligometastatic prostate cancer: definitions, clinical outcomes, and treatment considerations. Nat Rev Urol. 2017;14(1):15–25.CrossRefPubMedGoogle Scholar
  12. 12.
    Gravis G, Boher JM, Chen YH, Liu G, Fizazi K, Carducci MA, et al. Burden of metastatic castrate naive prostate cancer patients, to identify men more likely to benefit from early docetaxel: further analyses of CHAARTED and GETUG-AFU15 studies. Eur Urol. 2018;73:847–55.CrossRefPubMedGoogle Scholar
  13. 13.
    Gillessen S, Attard G, Beer TM, Beltran H, Bossi A, Bristow R, et al. Management of patients with advanced prostate cancer: the report of the advanced prostate cancer consensus conference APCCC 2017. Eur Urol. 2018;73(2):178–211.CrossRefPubMedGoogle Scholar
  14. 14.
    Auchus RJ, Yu MK, Nguyen S, Mundle SD. Use of prednisone with abiraterone acetate in metastatic castration-resistant prostate cancer. Oncologist. 2014;19:1231–40.CrossRefPubMedPubMedCentralGoogle Scholar
  15. 15.
    Ryan CJ, Smith MR, de Bono JS, Molina A, Logothetis CJ, de Souza P, et al. Abiraterone in metastatic prostate cancer without previous chemotherapy. N Engl J Med. 2013;368:138–48.CrossRefPubMedGoogle Scholar
  16. 16.
    Ryan CJ, Smith MR, Fizazi K, Saad F, Mulders PFA, Sternberg CN, et al. Abiraterone acetate plus prednisone versus placebo plus prednisone in chemotherapy-naive 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;16:152–60.CrossRefPubMedGoogle Scholar
  17. 17.
    Fizazi K, Scher HI, Molina A, Logothetis CJ, Chi KN, Jones RJ, et al. Abiraterone acetate for treatment of metastatic castration-resistant prostate cancer: final overall survival analysis of the COU-AA-301 randomised, double-blind, placebo-controlled phase 3 study. Lancet Oncol. 2012;13:983–92.CrossRefPubMedGoogle Scholar
  18. 18.
    Cheetham PJ, Petrylak DP. Re: abiraterone and increased survival in metastatic prostate cancer. Eur Urol. 2012;61:850.CrossRefPubMedGoogle Scholar
  19. 19.
    James ND, de Bono JS, Spears MR, Clarke NW, Mason MD, Dearnaley DP, et al. Abiraterone for prostate cancer not previously treated with hormone therapy. N Engl J Med. 2017;377:338–51.CrossRefPubMedPubMedCentralGoogle Scholar
  20. 20.
    Fizazi K, Tran N, Fein L, Matsubara N, Rodriguez-Antolin A, Alekseev BY, et al. Abiraterone plus prednisone in metastatic, castration-sensitive prostate cancer. N Engl J Med. 2017;377:352–60.CrossRefPubMedGoogle Scholar
  21. 21.
    Chi KN, Protheroe A, Rodríguez-Antolín A, Facchini G, Suttman H, Matsubara N, et al. Patient-reported outcomes following abiraterone acetate plus prednisone added to androgen deprivation therapy in patients with newly diagnosed metastatic castration-naive prostate cancer (LATITUDE): an international, randomised phase 3 trial. Lancet Oncol. 2018;19:194–206.CrossRefPubMedGoogle Scholar
  22. 22.
    Hoyle AP, Ali SA, James ND, Parker CC, Cook AD, Attard G, et al. LBA4 Effects of abiraterone acetate plus prednisone/prednisolone in high and low risk metastatic hormone sensitive prostate cancer. Ann Oncol. 2018;29 Suppl 8:mdy424.033.Google Scholar
  23. 23.
    Di Lorenzo G, Buonerba C. Hypercastration in prostate cancer. Expert Rev Endocrinol Metab. 2013;8:303–5.CrossRefPubMedGoogle Scholar
  24. 24.
    Gordon JA, Buonerba C, Pond G, Crona D, Gillessen S, Lucarelli G, et al. Statin use and survival in patients with metastatic castration-resistant prostate cancer treated with abiraterone or enzalutamide after docetaxel failure: the international retrospective observational STABEN study. Oncotarget. 2018;9(28):19861–73.CrossRefPubMedPubMedCentralGoogle Scholar
  25. 25.
    Szmulewitz RZ, Peer C, Ibraheem A, Martinez E, Kozloff MF, Carthon B, et al. Prospective international randomized phase II study of low-dose abiraterone with food versus standard dose abiraterone in castration-resistant prostate cancer. J Clin Oncol. 2018;36:1389–95.CrossRefPubMedGoogle Scholar
  26. 26.
    Attard G, Borre M, Gurney H, Loriot Y, Andresen-Daniil C, Kalleda R, et al. Abiraterone alone or in combination with enzalutamide in metastatic castration-resistant prostate cancer with rising prostate-specific antigen during enzalutamide treatment. J Clin Oncol. 2018;36:2639–46.CrossRefPubMedPubMedCentralGoogle Scholar
  27. 27.
    Smith MR, Parker CC, Saad F, Miller K, Tombal B, Ng QS, et al. LBA30 ERA 223: a phase III trial of radium-223 (Ra-223) in combination with abiraterone acetate and prednisone/prednisolone for the treatment of asymptomatic or mildly symptomatic chemotherapy-naïve patients (pts) with bone-predominant metastatic castratio. Ann Oncol. 2018;29 Suppl 8:mdy424.035.Google Scholar
  28. 28.
    Massard C, Mateo J, Loriot Y, Pezaro C, Albiges L, Mehra N, et al. Phase I/II trial of cabazitaxel plus abiraterone in patients with metastatic castration-resistant prostate cancer (mCRPC) progressing after docetaxel and abiraterone. Ann Oncol. 2017;28:90–5.PubMedGoogle Scholar
  29. 29.
    Scher HI, Fizazi K, Saad F, Taplin M-E, Sternberg CN, Miller K, et al. Increased survival with enzalutamide in prostate cancer after chemotherapy. N Engl J Med. 2012;367:1187–97.CrossRefPubMedGoogle Scholar
  30. 30.
    Fizazi K, Scher HI, Miller K, Basch E, Sternberg CN, Cella D, 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;15:1147–56.CrossRefPubMedGoogle Scholar
  31. 31.
    Beer TM, Armstrong AJ, Rathkopf DE, Loriot Y, Sternberg CN, Higano CS, et al. Enzalutamide in metastatic prostate cancer before chemotherapy. N Engl J Med. 2014;371:424–33.CrossRefPubMedPubMedCentralGoogle Scholar
  32. 32.
    Beer TM, Armstrong AJ, Rathkopf D, Loriot Y, Sternberg CN, Higano CS, et al. Enzalutamide in men with chemotherapy-naïve metastatic castration-resistant prostate cancer: extended analysis of the phase 3 PREVAIL study. Eur Urol. 2017;71:151–4.CrossRefPubMedGoogle Scholar
  33. 33.
    Hussain M, Fizazi K, Saad F, Rathenborg P, Shore N, Ferreira U, et al. Enzalutamide in men with nonmetastatic, castration-resistant prostate cancer. N Engl J Med. 2018;378:2465–74.CrossRefPubMedGoogle Scholar
  34. 34.
    Graff JN, Baciarello G, Armstrong AJ, Higano CS, Iversen P, Flaig TW, et al. Efficacy and safety of enzalutamide in patients 75 years or older with chemotherapy-naive metastatic castrationresistant prostate cancer: results from PREVAIL. Ann Oncol. 2016;27:286–94.CrossRefPubMedGoogle Scholar
  35. 35.
    Khalaf D, Annala M, Finch DL, Oja CD, Vergidis J, Zulfiqar M, et al. Phase 2 randomized cross-over trial of abiraterone + prednisone (ABI + P) vs enzalutamide (ENZ) for patients (pts) with metastatic castration resistant prostate cancer (mCPRC): results for 2nd-line therapy. J Clin Oncol. 2018;36:5015.CrossRefGoogle Scholar
  36. 36.
    de Bono JS, Chowdhury S, Feyerabend S, Elliott T, Grande E, Melhem-Bertrandt A, et al. Antitumour activity and safety of enzalutamide in patients with metastatic castration-resistant prostate cancer previously treated with abiraterone acetate plus prednisone for ≥ 24 weeks in Europe. Eur Urol. 2018;74:37–45.CrossRefPubMedGoogle Scholar
  37. 37.
    Clegg NJ, Wongvipat J, Joseph JD, Tran C, Ouk S, Dilhas A, et al. ARN-509: a novel antiandrogen for prostate cancer treatment. Cancer Res. 2012;72:1494–503.CrossRefPubMedPubMedCentralGoogle Scholar
  38. 38.
    Patel JC, Maughan BL, Agarwal AM, Batten JA, Zhang TY, Agarwal N. Emerging molecularly targeted therapies in castration refractory prostate cancer. Prostate Cancer. 2013;2013:1–12.CrossRefGoogle Scholar
  39. 39.
    Chong JT, Oh WK, Liaw BC. Profile of apalutamide in the treatment of metastatic castration-resistant prostate cancer: evidence to date. Onco Targets Ther. 2018;11:2141–7.CrossRefPubMedPubMedCentralGoogle Scholar
  40. 40.
    Smith MR, Saad F, Chowdhury S, Oudard S, Hadaschik BA, Graff JN, et al. Apalutamide treatment and metastasis-free survival in prostate cancer. N Engl J Med. 2018;378(15):1408–18.CrossRefPubMedGoogle Scholar
  41. 41.
    Shore ND. Darolutamide (ODM-201) for the treatment of prostate cancer. Expert Opin Pharmacother. 2017;18(9):945–52.CrossRefPubMedGoogle Scholar
  42. 42.
    Fizazi K, Massard C, Bono P, Jones R, Kataja V, James N, et al. Activity and safety of ODM-201 in patients with progressive metastatic castration-resistant prostate cancer (ARADES): an open-label phase 1 dose-escalation and randomised phase 2 dose expansion trial. Lancet Oncol. 2014;15(9):975–85.CrossRefPubMedGoogle Scholar
  43. 43.
    Fizazi K, Smith MR, Tombal B. Clinical development of darolutamide: a novel androgen receptor antagonist for the treatment of prostate cancer. Clin Genitourin Cancer. 2018;16(5):332–40.CrossRefPubMedGoogle Scholar
  44. 44.
    Phase III Trial of darolutamide in patients with non-metastatic castration-resistant prostate cancer meets primary endpoint. https://www.bayer.us/en/newsroom/press-releases/article/?id=123249.
  45. 45.
    Darshan MS, Loftus MS, Thadani-Mulero M, Levy BP, Escuin D, Zhou XK, et al. Taxane-induced blockade to nuclear accumulation of the androgen receptor predicts clinical responses in metastatic prostate cancer. Cancer Res. 2011;71:6019–29.CrossRefPubMedPubMedCentralGoogle Scholar
  46. 46.
    Tannock IF, de Wit R, Berry WR, Horti J, Pluzanska A, Chi KN, et al. Docetaxel plus prednisone or mitoxantrone plus prednisone for advanced prostate cancer. N Engl J Med. 2004;351:1502–12.CrossRefPubMedGoogle Scholar
  47. 47.
    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;26:242–5.CrossRefPubMedGoogle Scholar
  48. 48.
    Loriot Y, Eymard JC, Patrikidou A, Ileana E, Massard C, Albiges L, et al. Prior long response to androgen deprivation predicts response to next-generation androgen receptor axis targeted drugs in castration resistant prostate cancer. Eur J Cancer. 2015;51(14):1946–52.CrossRefPubMedGoogle Scholar
  49. 49.
    Italiano A, Ortholan C, Oudard S, Pouessel D, Gravis G, Beuzeboc P, et al. Docetaxel-based chemotherapy in elderly patients (age 75 and older) with castration-resistant prostate cancer. Eur Urol. 2009;55:1368–76.CrossRefPubMedGoogle Scholar
  50. 50.
    Feyerabend S, Saad F, Li T, Ito T, Diels J, Van Sanden S, et al. Survival benefit, disease progression and quality-of-life outcomes of abiraterone acetate plus prednisone versus docetaxel in metastatic hormone-sensitive prostate cancer: a network meta-analysis. Eur J Cancer. 2018;103:78–87.CrossRefPubMedGoogle Scholar
  51. 51.
    Vale CL, Fisher DJ, White IR, Carpenter JR, Burdett S, Clarke NW, et al. What is the optimal systemic treatment of men with metastatic, hormone-naive prostate cancer? A STOPCAP systematic review and network meta-analysis. Ann Oncol. 2018;29:1249–57.CrossRefPubMedPubMedCentralGoogle Scholar
  52. 52.
    Lavaud P, Gravis G, Foulon S, Joly F, Oudard S, Priou F, et al. Anticancer activity and tolerance of treatments received beyond progression in men treated upfront with androgen deprivation therapy with or without docetaxel for metastatic castration-naïve prostate cancer in the GETUG-AFU 15 Phase 3 trial. Eur Urol. 2018;73:696–703.CrossRefPubMedGoogle Scholar
  53. 53.
    Di Lorenzo G, Buonerba C, Faiella A, Rescigno P, Rizzo M, Autorino R, et al. Phase II study of docetaxel re-treatment in docetaxel-pretreated castration-resistant prostate cancer. BJU Int. 2011;107:234–9.CrossRefPubMedGoogle Scholar
  54. 54.
    Vrignaud P, Semiond D, Benning V, Beys E, Bouchard H, Gupta S. Preclinical profile of cabazitaxel. Drug Des Devel Ther. 2014;8:1851–67.CrossRefPubMedPubMedCentralGoogle Scholar
  55. 55.
    Bai S, Zhang B, Dong Y. Impact of taxanes on androgen receptor signaling. Asian J Androl. 2018;361:955–64.Google Scholar
  56. 56.
    de Bono JS, Oudard S, Ozguroglu M, Hansen S, Machiels J-P, Kocak I, et al. Prednisone plus cabazitaxel or mitoxantrone for metastatic castration-resistant prostate cancer progressing after docetaxel treatment: a randomised open-label trial. Lancet. 2010;376:1147–54.CrossRefPubMedGoogle Scholar
  57. 57.
    Lorenzo G, Daniello C, Buonerba C, Federico P, Rescigno P, Puglia L, et al. Peg-filgrastim and cabazitaxel in prostate cancer patients. Anticancer Drugs. 2013;24:84–9.CrossRefPubMedGoogle Scholar
  58. 58.
    Meisel A, Von Felten S, Vogt DR, Liewen H, De Wit R, De Bono J, et al. Severe neutropenia during cabazitaxel treatment is associated with survival benefit in men with metastatic castration-resistant prostate cancer (mCRPC): a post hoc analysis of the TROPIC phase III trial. Eur J Cancer. 2016;56:93–100.CrossRefPubMedGoogle Scholar
  59. 59.
    Nieuweboer AJM, De Graan AJM, Hamberg P, Bins S, Van Soest RJ, Van Alphen RJ, et al. Effects of budesonide on cabazitaxel pharmacokinetics and cabazitaxel-induced diarrhea: a randomized, open-label multicenter phase II study. Clin Cancer Res. 2017;23:1679–83.CrossRefPubMedGoogle Scholar
  60. 60.
    Omlin A, Sartor O, Rothermundt C, Cathomas R, De Bono JS, Shen L, et al. Analysis of side effect profile of alopecia, nail changes, peripheral neuropathy, and dysgeusia in prostate cancer patients treated with docetaxel and cabazitaxel. Clin Genitourin Cancer. 2015;13:e205–8.CrossRefPubMedGoogle Scholar
  61. 61.
    Di Lorenzo G, Bracarda S, Gasparro D, Gernone A, Messina C, Zagonel V, et al. Lack of cumulative toxicity associated with cabazitaxel use in prostate cancer. Medicine (Baltimore). 2016;95(2):e2299.CrossRefPubMedPubMedCentralGoogle Scholar
  62. 62.
    Atag E, Semiz HS, Kazaz SN, Tuna EB, Ozdogan O, Bozkurt O, et al. Response to cabazitaxel beyond 20 cycles in a patient with penile metastasis of prostate cancer: a case report. Urol J. 2017;14:2985–8.PubMedGoogle Scholar
  63. 63.
    Clément-Zhao A, Auvray M, Aboudagga H, Blanc-Durand F, Angelergues A, Vano YA, et al. Safety and efficacy of 2-weekly cabazitaxel in metastatic castration-resistant prostate cancer. BJU Int. 2018;121:203–8.CrossRefPubMedGoogle Scholar
  64. 64.
    Yachnin J, Gilje B, Thon K, Johansson H, Brandberg Y, Panaretakis T, et al. Weekly versus 3-weekly cabazitaxel for the treatment of castration-resistant prostate cancer: a randomised phase II trial (ConCab). Eur J Cancer. 2018;97:33–40.CrossRefPubMedGoogle Scholar
  65. 65.
    Buonerba C, Pond GR, Sonpavde G, Federico P, Rescigno P, Puglia L, et al. Potential value of Gleason score in predicting the benefit of cabazitaxel in metastatic castration-resistant prostate cancer. Futur Oncol. 2013;9:889–97.CrossRefGoogle Scholar
  66. 66.
    De Placido S, Rescigno P, Federico P, Buonerba C, Bosso D, Puglia L, et al. Cabazitaxel in castration resistant prostate cancer with brain metastases: 3 case reports. World J Clin Cases. 2014;2:228–31.CrossRefPubMedPubMedCentralGoogle Scholar
  67. 67.
    Di Lorenzo G, Buonerba C, De Placido S. Rapidly progressive disease in a castration-resistant prostate cancer patient after cabazitaxel discontinuation. Anticancer Drugs. 2015;26:236–9.CrossRefPubMedGoogle Scholar
  68. 68.
    Eisenberger M, Hardy-Bessard AC, Kim CS, Géczi L, Ford D, Mourey L, et al. Phase III study comparing a reduced dose of cabazitaxel (20 mg/m2) and the currently approved dose (25 mg/m2) in postdocetaxel patients with metastatic castration-resistant prostate cancer—PROSELICA. J Clin Oncol. 2017;35:3198–206.CrossRefPubMedGoogle Scholar
  69. 69.
    Oudard S, Fizazi K, Sengeløv L, Daugaard G, Saad F, Hansen S, et al. Cabazitaxel versus docetaxel as first-line therapy for patients with metastatic castration-resistant prostate cancer: a randomized phase III trial—FIRSTANA. J Clin Oncol. 2017;35:3189–97.CrossRefPubMedGoogle Scholar
  70. 70.
    Al Nakouzi N, Le Moulec S, Albigès L, Wang C, Beuzeboc P, Gross-Goupil M, et al. Cabazitaxel remains active in patients progressing after docetaxel followed by novel androgen receptor pathway targeted therapies. Eur Urol. 2015;68:228–35.CrossRefPubMedGoogle Scholar
  71. 71.
    Di Lorenzo G, Bracarda S, Buonerba C, Aieta M, Mirone V. Poor survival in prostate cancer patients with primary refractoriness to docetaxel. Eur Urol. 2014;65:505–7.CrossRefPubMedGoogle Scholar
  72. 72.
    Antonarakis ES, Tagawa ST, Galletti G, Worroll D, Ballman K, Vanhuyse M, et al. Randomized, noncomparative, phase II trial of early switch from docetaxel to cabazitaxel or vice versa, with integrated biomarker analysis, in men with chemotherapy-naïve, metastatic, castration-resistant prostate cancer. J Clin Oncol. 2017;35:3181–8.CrossRefPubMedPubMedCentralGoogle Scholar
  73. 73.
    Buonerba C, Sonpavde G, Vitrone F, Bosso D, Puglia L, Izzo M, et al. The influence of prednisone on the efficacy of cabazitaxel in men with metastatic castration-resistant prostate cancer. J Cancer. 2017;8:2663–8.CrossRefPubMedPubMedCentralGoogle Scholar
  74. 74.
    Ferro M, Di Lorenzo G, de Cobelli O, Bruzzese D, Pignataro P, Borghesi M, et al. Incidence of fatigue and low-dose corticosteroid use in prostate cancer patients receiving systemic treatment: a meta-analysis of randomized controlled trials. World J Urol. 2018;1:4.  https://doi.org/10.1007/s00345-018-2579-x (Epub 5 Dec 2018).CrossRefGoogle Scholar
  75. 75.
    Buonerba C, Bosso D, De Placido S, Di Lorenzo G. 841TiPA randomized phase II study comparing cabazitaxel/prednisone to cabazitaxel alone for second-line chemotherapy in men with metastatic castrate resistant prostate cancer (mCRPC): CABACARE. Ann Oncol. 2017;28(Suppl):5.Google Scholar
  76. 76.
    Taneja SS. Re: alpha emitter radium-223 and survival in metastatic prostate cancer. J Urol. 2014;191:657.CrossRefPubMedGoogle Scholar
  77. 77.
    Sartor O, Coleman R, Nilsson S, Heinrich D, Helle SI, O’Sullivan JM, et al. Effect of radium-223 dichloride on symptomatic skeletal events in patients with castration-resistant prostate cancer and bone metastases: results from a phase 3, double-blind, randomised trial. Lancet Oncol. 2014;15:738–46.CrossRefPubMedGoogle Scholar
  78. 78.
    Saad F, Carles J, Gillessen S, Heidenreich A, Heinrich D, Gratt J, et al. Radium-223 and concomitant therapies in patients with metastatic castration-resistant prostate cancer: an international, early access, open-label, single-arm phase 3b trial. Lancet Oncol. 2016;17:1306–16.CrossRefPubMedGoogle Scholar
  79. 79.
    Hofman MS, Violet J, Hicks RJ, Ferdinandus J, Ping Thang S, Akhurst T, et al. [177Lu]-PSMA-617 radionuclide treatment in patients with metastatic castration-resistant prostate cancer (LuPSMA trial): a single-centre, single-arm, phase 2 study. Lancet Oncol. 2018;19:825–33.CrossRefPubMedGoogle Scholar
  80. 80.
    Kim YJ, Kim Y. Therapeutic responses and survival effects of 177Lu-PSMA-617 radioligand therapy in metastatic castrate-resistant prostate cancer: a meta-analysis. Clin Nucl Med. 2018;43:728–34.CrossRefPubMedGoogle Scholar
  81. 81.
    Deeks ED. Olaparib: first global approval. Drugs. 2015;75:231–40.CrossRefPubMedGoogle Scholar
  82. 82.
    Robson M, Im S-A, Senkus E, Xu B, Domchek SM, Masuda N, et al. Olaparib for metastatic breast cancer in patients with a germline BRCA mutation. N Engl J Med. 2017;377(6):523–33.CrossRefPubMedGoogle Scholar
  83. 83.
    Ledermann J, Harter P, Gourley C, Friedlander M, Vergote I, Rustin G, et al. Olaparib maintenance therapy in platinum-sensitive relapsed ovarian cancer. N Engl J Med. 2012;366(15):1382–92.CrossRefPubMedGoogle Scholar
  84. 84.
    Mateo J, Carreira S, Sandhu S, Miranda S, Mossop H, Perez-Lopez R, et al. DNA-repair defects and olaparib in metastatic prostate cancer. N Engl J Med. 2015;373:1697–708.CrossRefPubMedPubMedCentralGoogle Scholar
  85. 85.
    Syed YY. Rucaparib: first global approval. Drugs. 2017;77:585–92.CrossRefPubMedGoogle Scholar
  86. 86.
    Abida W, Bryce AH, Vogelzang NJ, Amato RJ, Percent I, Shapiro JD, et al. 793PD preliminary results from TRITON2: a phase II study of rucaparib in patients (pts) with metastatic castration-resistant prostate cancer (mCRPC) associated with homologous recombination repair (HRR) gene alterations. Ann Oncol. 2018;29 Suppl 8:mdy284.002.Google Scholar
  87. 87.
    Scott LJ. Niraparib: first global approval. Drugs. 2017;77:1029–34.CrossRefPubMedGoogle Scholar
  88. 88.
    Buonerba C, Di Lorenzo G, Sonpavde G. Contemporary molecular tests for prognosis and treatment guidance for castration-resistant prostate cancer. Expert Rev Mol Diagn. 2016;16(10):1113–20.CrossRefPubMedGoogle Scholar
  89. 89.
    Goodall J, Mateo J, Yuan W, Mossop H, Porta N, Miranda S, et al. Circulating cell-free DNA to guide prostate cancer treatment with PARP inhibition. Cancer Discov. 2017;7:1006–17.CrossRefPubMedPubMedCentralGoogle Scholar
  90. 90.
    Zhou D, Xu J, Mpoy C, Chu W, Kim SH, Li H, et al. Preliminary evaluation of a novel 18F-labeled PARP-1 ligand for PET imaging of PARP-1 expression in prostate cancer. Nucl Med Biol. 2018;66:26–31.CrossRefPubMedGoogle Scholar
  91. 91.
    Di Lorenzo G, Ferro M, Buonerba C. Sipuleucel-T (Provenge®) for castration-resistant prostate cancer. BJU Int. 2012;110(2 Pt 2):E99–104.CrossRefPubMedGoogle Scholar
  92. 92.
    Buonerba C, Ferro M, Di Lorenzo G. Sipuleucel-T for prostate cancer: the immunotherapy era has commenced. Expert Rev Anticancer Ther. 2011;11:25–8.CrossRefPubMedGoogle Scholar
  93. 93.
    Kantoff PW, Higano CS, Shore ND, Berger ER, Small EJ, Penson DF, et al. Sipuleucel-T immunotherapy for castration-resistant prostate cancer. N Engl J Med. 2010;363:411–22.CrossRefPubMedGoogle Scholar
  94. 94.
    Cameron F, Whiteside G, Perry C. Ipilimumab: first global approval. Drugs. 2011;71(8):1093–104.CrossRefPubMedGoogle Scholar
  95. 95.
    Kwon ED, Drake CG, Scher HI, Fizazi K, Bossi A, van den Eertwegh AJM, et al. Ipilimumab versus placebo after radiotherapy in patients with metastatic castration-resistant prostate cancer that had progressed after docetaxel chemotherapy (CA184-043): a multicentre, randomised, double-blind, phase 3 trial. Lancet Oncol. 2014;15:700–12.CrossRefPubMedPubMedCentralGoogle Scholar
  96. 96.
    Fizazi K, Drake CG, Kwon ED, Bossi A, van den Eertwegh AJ, Scher HI, et al. 763PD updated overall survival (OS) from the phase 3 tRIAL, CA184-043: ipilimumab (IPI) vs placebo (PBO) in patients with post-docetaxel metastatic castration-resistant prostate cancer (MCRPC). Ann Oncol. 2014;25:iv259–60.CrossRefGoogle Scholar
  97. 97.
    Beer TM, Kwon ED, Drake CG, Fizazi K, Logothetis C, Gravis G, et al. Randomized, double-blind, phase III trial of ipilimumab versus placebo in asymptomatic or minimally symptomatic patients with metastatic chemotherapy-naive castration-resistant prostate cancer. J Clin Oncol. 2017;35:40–7.CrossRefPubMedGoogle Scholar
  98. 98.
    Boudadi K, Suzman DL, Anagnostou V, Fu W, Luber B, Wang H, et al. Ipilimumab plus nivolumab and DNA-repair defects in AR-V7-expressing metastatic prostate cancer. Oncotarget. 2018;9(47):28561–71.CrossRefPubMedPubMedCentralGoogle Scholar
  99. 99.
    Wang M, Ma X, Guo L, Xia F. Safety and efficacy profile of pembrolizumab in solid cancer: pooled reanalysis based on randomized controlled trials. Drug Des Dev Ther. 2017;11:2851–60.CrossRefGoogle Scholar
  100. 100.
    De Bono JS, Goh JCH, Ojamaa K, Piulats Rodriguez JM, Drake CG, Hoimes CJ, et al. KEYNOTE-199: pembrolizumab (pembro) for docetaxel-refractory metastatic castration-resistant prostate cancer (mCRPC). J Clin Oncol. 2018;36(15 Suppl):5007.CrossRefGoogle Scholar
  101. 101.
    Graff JN, Alumkal JJ, Thompson RF, Moran A, Thomas GV, Wood MA, et al. Pembrolizumab (Pembro) plus enzalutamide (Enz) in metastatic castration resistant prostate cancer (mCRPC): extended follow up. J Clin Oncol. 2018;36(15 Suppl):5047.CrossRefGoogle Scholar
  102. 102.
    Yu EY, Wu H, Schloss C. Phase 1b/2 keynote-365 trial: Pembrolizumab (pembro) combination therapy in metastatic castration-resistant prostate cancer (mCRPC) [abstract no TPS5089J]. Clin Oncol. 2017;35.Google Scholar
  103. 103.
    Abida W, Cheng ML, Armenia J, Middha S, Autio KA, Vargas HA, et al. Analysis of the prevalence of microsatellite instability in prostate cancer and response to immune checkpoint blockade. JAMA Oncol. 2018;1:4.  https://doi.org/10.1001/jamaoncol.2018.5801 (Epub 27 Dec 2018).CrossRefGoogle Scholar
  104. 104.
    Sternberg C, Armstrong A, Pili R, Ng S, Huddart R, Agarwal N, et al. Randomized, double-blind, placebo-controlled phase III study of tasquinimod in men with metastatic castration-resistant prostate cancer. J Clin Oncol. 2016;34:2636–43.CrossRefPubMedGoogle Scholar
  105. 105.
    Fizazi K, Ulys A, Sengeløv L, Moe M, Ladoire S, Thiery-Vuillemin A, et al. A randomized, double-blind, placebo-controlled phase II study of maintenance therapy with tasquinimod in patients with metastatic castration-resistant prostate cancer responsive to or stabilized during first-line docetaxel chemotherapy. Ann Oncol. 2017;28:2741–6.CrossRefPubMedPubMedCentralGoogle Scholar
  106. 106.
    Sydes MR, Spears MR, Mason MD, Clarke NW, Dearnaley DP, de Bono JS, et al. Adding abiraterone or docetaxel to long-term hormone therapy for prostate cancer: directly randomised data from the STAMPEDE multi-arm, multi-stage platform protocol. Ann Oncol. 2018;29:1235–48.CrossRefPubMedPubMedCentralGoogle Scholar
  107. 107.
    de Bono JS, Logothetis CJ, Molina A, Fizazi K, North S, Chu L, et al. Abiraterone and increased survival in metastatic prostate cancer. N Engl J Med. 2011;364:1995–2005.CrossRefPubMedPubMedCentralGoogle Scholar
  108. 108.
    Parker C, Nilsson S, Heinrich D, Helle SI, O’Sullivan JM, Fosså SD, et al. Alpha emitter radium-223 and survival in metastatic prostate cancer. N Engl J Med. 2013;369:213–23.CrossRefPubMedGoogle Scholar
  109. 109.
    Sonpavde G, Huang A, Wang L, Baser O, Miao R. Taxane chemotherapy vs antiandrogen agents as first-line therapy for metastatic castration-resistant prostate cancer. BJU Int. 2018;121(6):871–9.CrossRefPubMedGoogle Scholar

Copyright information

© Springer Nature Switzerland AG 2019

Authors and Affiliations

  • Martina Pagliuca
    • 1
  • Carlo Buonerba
    • 1
    • 2
  • Karim Fizazi
    • 3
  • Giuseppe Di Lorenzo
    • 1
    • 4
    Email author
  1. 1.Department of Clinical Medicine and SurgeryUniversity Federico II of NaplesNaplesItaly
  2. 2.Experimental Zoo-prophylactic Institute of Southern ItalyPorticiItaly
  3. 3.Institut Gustave Roussy, University of Paris SudVillejuifFrance
  4. 4.Department of MedicineUniversità degli Studi del MoliseCampobassoItaly

Personalised recommendations