The evolving landscape of PARP inhibitors in castration-resistant prostate cancer: a spotlight on treatment combinations

References

• Siegel RL, Miller KD, Fuchs HE, et al. Cancer statistics, 2022. CA Cancer J Clin. 2022 Jan;72(1):7–33.
   Google Scholar
• Sayegh N, Swami U, Agarwal N. Recent advances in the management of metastatic prostate cancer. JCO Oncol Pract. 2022 Jan;18(1):45–55.
   Google Scholar
• Sharifi N, Gulley JL, Dahut WL. Androgen deprivation therapy for prostate cancer. JAMA. 2005 Jul 13;294(2):238–244.
   Google Scholar
• Scher HI, Halabi S, Tannock I, et al. Design and end points of clinical trials for patients with progressive prostate cancer and castrate levels of testosterone: recommendations of the prostate cancer clinical trials working group. J Clin Oncol. 2008 Mar 1;26(7):1148–1159.
   Google Scholar
• Kawai AT, Martinez D, Saltus CW, et al. Incidence of skeletal-related events in patients with castration-resistant prostate cancer: an observational retrospective cohort study in the US. Prostate Cancer. 2019;2019:5971615.
   Google Scholar
• Tannock IF, de Wit R, Berry WR, et al. Docetaxel plus prednisone or mitoxantrone plus prednisone for advanced prostate cancer. N Engl J Med. 2004 Oct 7;351(15):1502–1512.
   Google Scholar
• de Bono JS, Oudard S, Ozguroglu M, et al. Prednisone plus cabazitaxel or mitoxantrone for metastatic castration-resistant prostate cancer progressing after docetaxel treatment: a randomised open-label trial. Lancet. 2010 Oct 2;376(9747):1147–1154.
   Google Scholar
• Beer TM, Armstrong AJ, Rathkopf DE, et al. Enzalutamide in metastatic prostate cancer before chemotherapy. N Engl J Med. 2014 Jul 31;371(5):424–433.
   Google Scholar
• Ryan CJ, Smith MR, de Bono JS, et al. Abiraterone in metastatic prostate cancer without previous chemotherapy. N Engl J Med. 2013 Jan 10;368(2):138–148.
   Google Scholar
• de Bono JS, Logothetis CJ, Molina A, et al. Abiraterone and increased survival in metastatic prostate cancer. N Engl J Med. 2011 May 26;364(21):1995–2005.
   Google Scholar
• Scher HI, Fizazi K, Saad F, et al. Increased survival with enzalutamide in prostate cancer after chemotherapy. N Engl J Med. 2012 Sep 27;367(13):1187–1197.
   Google Scholar
• Parker C, Nilsson S, Heinrich D, et al. Alpha emitter radium-223 and survival in metastatic prostate cancer. N Engl J Med. 2013 Jul 18;369(3):213–223.
   Google Scholar
• Sartor O, de Bono J, Chi KN, et al. Lutetium-177-PSMA-617 for metastatic castration-resistant prostate cancer. N Engl J Med. 2021 Sep 16;385(12):1091–1103.
   Google Scholar
• Kantoff PW, Higano CS, Shore ND, et al. Sipuleucel-T immunotherapy for castration-resistant prostate cancer. N Engl J Med. 2010 Jul 29;363(5):411–422.
   Google Scholar
• Sweeney CJ, Chen YH, Carducci M, et al. Chemohormonal therapy in metastatic hormone-sensitive prostate cancer. N Engl J Med. 2015 Aug 20;373(8):737–746.
   Google Scholar
• Fizazi K, Tran N, Fein L, et al. Abiraterone plus prednisone in metastatic, castration-sensitive prostate cancer. N Engl J Med. 2017 Jul 27;377(4):352–360.
   Google Scholar
• Davis ID, Martin AJ, Stockler MR, et al. Enzalutamide with standard first-line therapy in metastatic prostate cancer. N Engl J Med. 2019 Jul 11;381(2):121–131.
   Google Scholar
• Chi KN, Agarwal N, Bjartell A, et al. Apalutamide for metastatic, castration-sensitive prostate cancer. N Engl J Med. 2019 Jul 4;381(1):13–24.
   Google Scholar
• Fizazi K, Foulon S, Carles J, et al. Abiraterone plus prednisone added to androgen deprivation therapy and docetaxel in de novo metastatic castration-sensitive prostate cancer (PEACE-1): a multicentre, open-label, randomised, phase 3 study with a 2 x 2 factorial design. Lancet. 2022 Apr 30;399(10336):1695–1707.
   Google Scholar
• Smith MR, Hussain M, Saad F, et al. Darolutamide and survival in metastatic, hormone-sensitive prostate cancer. N Engl J Med. 2022 Mar 24;386(12):1132–1142.
   Google Scholar
• Smith MR, Saad F, Chowdhury S, et al. Apalutamide and overall survival in prostate cancer. Eur Urol. 2021 Jan;79(1):150–158.
   Google Scholar
• Sternberg CN, Fizazi K, Saad F, et al. Enzalutamide and survival in nonmetastatic, castration-resistant prostate cancer. N Engl J Med. 2020 Jun 4;382(23):2197–2206.
   Google Scholar
• Fizazi K, Shore N, Tammela TL, et al. Nonmetastatic, castration-resistant prostate cancer and survival with darolutamide. N Engl J Med. 2020 Sep 10;383(11):1040–1049.
   Google Scholar
• de Bono J, Mateo J, Fizazi K, et al. Olaparib for metastatic castration-resistant prostate cancer. N Engl J Med. 2020 May 28;382(22):2091–2102.
   Google Scholar
• Fong PC, Boss DS, Yap TA, et al. Inhibition of poly(ADP-ribose) polymerase in tumors from BRCA mutation carriers. N Engl J Med. 2009 Jul 9;361(2):123–134.
   Google Scholar
• Farmer H, McCabe N, Lord CJ, et al. Targeting the DNA repair defect in BRCA mutant cells as a therapeutic strategy. Nature. 2005 Apr 14;434(7035):917–921.
   Google Scholar
• Lord CJ, Ashworth A. PARP inhibitors: synthetic lethality in the clinic. Science. 2017 Mar 17;355(6330):1152–1158.
   Google Scholar
• Mateo J, Carreira S, Sandhu S, et al. DNA-repair defects and olaparib in metastatic prostate cancer. N Engl J Med. 2015 Oct 29;373(18):1697–1708.
   Google Scholar
• Mateo J, Porta N, Bianchini D, et al. Olaparib in patients with metastatic castration-resistant prostate cancer with DNA repair gene aberrations (TOPARP-B): a multicentre, open-label, randomised, phase 2 trial. Lancet Oncol. 2020 Jan;21(1):162–174.
   Google Scholar
• Hussain M, Mateo J, Fizazi K, et al. Survival with olaparib in metastatic castration-resistant prostate cancer. N Engl J Med. 2020 Dec 10;383(24):2345–2357.
   Google Scholar
• Risdon EN, Chau CH, Price DK, et al. PARP inhibitors and prostate cancer: to infinity and beyond BRCA. Oncologist. 2021 Jan;26(1):e115–e129.
   Google Scholar
• Schaeffer E, Srinivas S, Antonarakis ES, et al. NCCN guidelines insights: prostate cancer, version 1.2021. J Natl Compr Canc Netw. 2021 Feb 2;19(2):134–143.
   Google Scholar
• Caffo O, De Giorgi U, Fratino L, et al. Clinical outcomes of castration-resistant prostate cancer treatments administered as third or fourth line following failure of docetaxel and other second-line treatment: results of an Italian multicentre study. Eur Urol. 2015 Jul;68(1):147–153.
   Google Scholar
• Loriot Y, Bianchini D, Ileana E, et al. Antitumour activity of Abiraterone acetate against metastatic castration-resistant prostate cancer progressing after docetaxel and enzalutamide (MDV3100). Ann Oncol. 2013 Jul;24(7):1807–1812.
   Google Scholar
• Maughan BL, Luber B, Nadal R, et al. Comparing sequencing of abiraterone and enzalutamide in men with metastatic castration-resistant prostate cancer: a retrospective study. Prostate. 2017 Jan;77(1):33–40.
   Google Scholar
• Noonan KL, North S, Bitting RL, et al. Clinical activity of abiraterone acetate in patients with metastatic castration-resistant prostate cancer progressing after enzalutamide. Ann Oncol. 2013 Jul;24(7):1802–1807.
   Google Scholar
• Azad AA, Eigl BJ, Murray RN, et al. Efficacy of enzalutamide following abiraterone acetate in chemotherapy-naive metastatic castration-resistant prostate cancer patients. Eur Urol. 2015 Jan;67(1):23–29.
   Google Scholar
• Badrising S, van der Noort V, van Oort IM, et al. Clinical activity and tolerability of enzalutamide (MDV3100) in patients with metastatic, castration-resistant prostate cancer who progress after docetaxel and abiraterone treatment. Cancer. 2014 Apr 1;120(7):968–975.
   Google Scholar
• Bianchini D, Lorente D, Rodriguez-Vida A, et al. Antitumour activity of enzalutamide (MDV3100) in patients with metastatic castration-resistant prostate cancer (CRPC) pre-treated with docetaxel and Abiraterone. Eur J Cancer. 2014 Jan;50(1):78–84.
   Google Scholar
• Brasso K, Thomsen FB, Schrader AJ, et al. Enzalutamide antitumour activity against metastatic castration-resistant prostate cancer previously treated with docetaxel and abiraterone: a multicentre analysis. Eur Urol. 2015 Aug;68(2):317–324.
   Google Scholar
• Suzman DL, Luber B, Schweizer MT, et al. Clinical activity of enzalutamide versus docetaxel in men with castration-resistant prostate cancer progressing after Abiraterone. Prostate. 2014 Sep;74(13):1278–1285.
   Google Scholar
• Khalaf DJ, Annala M, Taavitsainen S, et al. Optimal sequencing of enzalutamide and abiraterone acetate plus prednisone in metastatic castration-resistant prostate cancer: a multicentre, randomised, open-label, phase 2, crossover trial. Lancet Oncol. 2019 Dec;20(12):1730–1739.
   Google Scholar
• Valabrega G, Scotto G, Tuninetti V, et al. Differences in PARP inhibitors for the treatment of ovarian cancer: mechanisms of action, pharmacology, safety, and efficacy. Int J Mol Sci. 2021 Apr 19;22(8):4203.
   Google Scholar
• Abida W, Patnaik A, Campbell D, et al. Rucaparib in men with metastatic castration-resistant prostate cancer harboring a BRCA1 or BRCA2 gene alteration. J Clin Oncol. 2020 Nov 10;38(32):3763–3772.
   Google Scholar
• Scher HI, Morris MJ, Stadler WM, et al. Trial design and objectives for castration-resistant prostate cancer: updated recommendations from the prostate cancer clinical trials working group 3. J Clin Oncol. 2016 Apr 20;34(12):1402–1418.
   Google Scholar
• Anscher MS, Chang E, Gao X, et al. FDA approval summary: rucaparib for the treatment of patients with deleterious BRCA-mutated metastatic castrate-resistant prostate cancer. Oncologist. 2021 Feb;26(2):139–146.
   Google Scholar
• Abida W, Campbell D, Patnaik A, et al. Non-BRCA DNA damage repair gene alterations and response to the PARP inhibitor rucaparib in metastatic castration-resistant prostate cancer: analysis from the phase II TRITON2 study. Clin Cancer Res. 2020 Jun 1;26(11):2487–2496.
   Google Scholar
• Ryan CJ, Abida W, Bryce AH, et al. TRITON3: an international, randomized, open-label, phase III study of the PARP inhibitor rucaparib vs. physician’s choice of therapy for patients with metastatic castration-resistant prostate cancer (mCRPC) associated with homologous recombination deficiency (HRD). J clin oncol. 2018;36(6_suppl): TPS389–TPS389.
   Google Scholar
• Hoy SM. Talazoparib: first Global Approval. Drugs. 2018 Dec;78(18):1939–1946.
   Google Scholar
• Washington CR, Moore KN. PARP inhibitors in the treatment of ovarian cancer: a review. Curr Opin Obstet Gynecol. 2021 Feb 1;33(1):1–6.
   Google Scholar
• Ison G, Howie LJ, Amiri-Kordestani L, et al. FDA approval summary: niraparib for the maintenance treatment of patients with recurrent ovarian cancer in response to platinum-based chemotherapy. Clin Cancer Res. 2018 Sep 1;24(17):4066–4071.
   Google Scholar
• Hussain M, Daignault-Newton S, Twardowski PW, et al. Targeting androgen receptor and DNA repair in metastatic castration-resistant prostate cancer: results from NCI 9012. J Clin Oncol. 2018 Apr 1;36(10):991–999.
   Google Scholar
• Sandhu SK, Schelman WR, Wilding G, et al. The poly(ADP-ribose) polymerase inhibitor niraparib (MK4827) in BRCA mutation carriers and patients with sporadic cancer: a phase 1 dose-escalation trial. Lancet Oncol. 2013 Aug;14(9):882–892.
   Google Scholar
• Smith MR, Scher HI, Sandhu S, et al. Niraparib in patients with metastatic castration-resistant prostate cancer and DNA repair gene defects (GALAHAD): a multicentre, open-label, phase 2 trial. Lancet Oncol. 2022 Mar;23(3):362–373.
   Google Scholar
• de Bono JS, Mehra N, Scagliotti GV, et al. Talazoparib monotherapy in metastatic castration-resistant prostate cancer with DNA repair alterations (TALAPRO-1): an open-label, phase 2 trial. Lancet Oncol. 2021 Sep;22(9):1250–1264.
   Google Scholar
• Murai J, Huang SY, Das BB, et al. Trapping of PARP1 and PARP2 by Clinical PARP Inhibitors. Cancer Res. 2012 Nov 1;72(21):5588–5599.
   Google Scholar
• Asim M, Tarish F, Zecchini HI, et al. Synthetic lethality between androgen receptor signalling and the PARP pathway in prostate cancer. Nat Commun. 2017 Aug 29;8(1):374.
   Google Scholar
• Clarke N, Wiechno P, Alekseev B, et al. Olaparib combined with Abiraterone in patients with metastatic castration-resistant prostate cancer: a randomised, double-blind, placebo-controlled, phase 2 trial. Lancet Oncol. 2018 Jul;19(7):975–986.
   Google Scholar
• Clarke NW, Armstrong AJ, Thiery-Vuillemin A, et al. Abiraterone and olaparib for metastatic castration-resistant prostate cancer. NEJM Evidence. 2022. EVIDoa2200043. •• Significant progression-free survival benefit in both HRRd and non-HRRd patients for combination olaparib plus abiraterone.
   Google Scholar
• Chi KN, Rathkopf DE, Smith MR, et al. Phase 3 MAGNITUDE study: first results of niraparib (NIRA) with abiraterone acetate and prednisone (AAP) as first-line therapy in patients (pts) with metastatic castration-resistant prostate cancer (mCRPC) with and without homologous recombination repair (HRR) gene alterations. J clin oncol. 2022;40(6_suppl):12.
   Google Scholar
• Li L, Karanika S, Yang G, et al. Androgen receptor inhibitor-induced “BRCAness” and PARP inhibition are synthetically lethal for castration-resistant prostate cancer. Sci Signal. 2017 May 23;10(480). DOI:10.1126/scisignal.aam7479.
   Google Scholar
• Rao A, Heller G, Ryan CJ, et al. Alliance A031902 (CASPAR): a randomized, phase (ph) 3 trial of enzalutamide with rucaparib/placebo in first-line metastatic castration-resistant prostate cancer (mCRPC). J clin oncol. 2022;40(16_suppl): TPS5107–TPS5107.
   Google Scholar
• Agarwal N, Shore ND, Dunshee C, et al. TALAPRO-2: a placebo-controlled phase III study of talazoparib (TALA) plus enzalutamide (ENZA) for patients with first-line metastatic castration-resistant prostate cancer (mCRPC). J clin oncol. 2020;38(15_suppl): TPS5598–TPS5598.
   Google Scholar
• Hussain M, Carducci MA, Slovin S, et al. Targeting DNA repair with combination veliparib (ABT-888) and temozolomide in patients with metastatic castration-resistant prostate cancer. Invest New Drugs. 2014 Oct;32(5):904–912.
   Google Scholar
• Murai J, Zhang Y, Morris J, et al. Rationale for poly(ADP-ribose) polymerase (PARP) inhibitors in combination therapy with camptothecins or temozolomide based on PARP trapping versus catalytic inhibition. J Pharmacol Exp Ther. 2014 Jun;349(3):408–416.
   Google Scholar
• Thompson CA. FDA approves prostate cancer treatment that inhibits testosterone synthesis. Am J Health Syst Pharm. 2011 Jun 1;68(11):960.
   Google Scholar
• Teply BA, Hauke RJ. Chemotherapy options in castration-resistant prostate cancer. Indian J Urol. 2016 Oct-Dec;32(4):262–270.
   Google Scholar
• Calabrese CR, Almassy R, Barton S, et al. Anticancer chemosensitization and radiosensitization by the novel poly(ADP-ribose) polymerase-1 inhibitor AG14361. J Natl Cancer Inst. 2004 Jan 7;96(1):56–67.
   Google Scholar
• Shaya J, Xie W, Saraiya B, et al. A phase I/II study of combination olaparib and radium-223 in men with metastatic castration-resistant prostate cancer with bone metastases (COMRADE): a trial in progress. J clin oncol. 2021;39(6_suppl): TPS182–TPS182.
   Google Scholar
• McKay RR, Xie W, Ajmera A, et al. Updated biomarker results from a phase 1/2 study of olaparib and radium-223 in men with metastatic castration-resistant prostate cancer (mCRPC) with bone metastases (COMRADE). J clin oncol. 2022;40(6_suppl):119.
   Google Scholar
• Powles T, Yuen KC, Gillessen S, et al. Atezolizumab with enzalutamide versus enzalutamide alone in metastatic castration-resistant prostate cancer: a randomized phase 3 trial. Nat Med. 2022 Jan;28(1):144–153.
   Google Scholar
• Beer TM, Kwon ED, Drake CG, 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 Jan;35(1):40–47.
   Google Scholar
• Kwon ED, Drake CG, Scher HI, 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 Jun;15(7):700–712.
   Google Scholar
• Karzai F, VanderWeele D, Madan RA, et al. Activity of durvalumab plus olaparib in metastatic castration-resistant prostate cancer in men with and without DNA damage repair mutations. J Immunother Cancer. 2018 Dec 4;6(1):141.
   Google Scholar
• Petrylak DP, Perez-Gracia JL, Lacombe L, et al. 579MO CheckMate 9KD cohort A2 final analysis: nivolumab (NIVO) + rucaparib for chemotherapy (CT)-naive metastatic castration-resistant prostate cancer (mCRPC). Ann Oncol. 2021;32:S629–S630.
   Google Scholar
• Pachynski RK, Retz M, Goh JC, et al. CheckMate 9KD cohort A1 final analysis: nivolumab (NIVO) + rucaparib for post-chemotherapy (CT) metastatic castration-resistant prostate cancer (mCRPC). J clin oncol. 2021;39(15_suppl):5044.
   Google Scholar
• Yu EY, Piulats JM, Gravis G, et al. KEYNOTE-365 cohort A updated results: pembrolizumab (pembro) plus olaparib in docetaxel-pretreated patients (pts) with metastatic castration-resistant prostate cancer (mCRPC). J clin oncol. 2020;38(6_suppl):100.
   Google Scholar
• Yu EY, Park SH, Huang Y-H, et al. Phase III study of pembrolizumab (pembro) plus olaparib versus enzalutamide (enza) or Abiraterone acetate (abi) in patients (pts) with metastatic castration-resistant prostate cancer (mCRPC) who progressed on chemotherapy: KEYLYNK-010. J clin oncol. 2020;38(6_suppl): TPS256–TPS256.
   Google Scholar
• Reichert ZR, Devitt ME, Alumkal JJ, et al. Targeting resistant prostate cancer, with or without DNA repair defects, using the combination of ceralasertib (ATR inhibitor) and olaparib (the TRAP trial). J clin oncol. 2022;40(6_suppl):88.
   Google Scholar
• Denmeade SR, Wang H, Agarwal N, et al. TRANSFORMER: a randomized phase II study comparing bipolar androgen therapy versus enzalutamide in asymptomatic men with castration-resistant metastatic prostate cancer. J Clin Oncol. 2021 Apr 20;39(12):1371–1382.
   Google Scholar
• Denmeade SR, Isaacs JT. Bipolar androgen therapy: the rationale for rapid cycling of supraphysiologic androgen/ablation in men with castration resistant prostate cancer. Prostate. 2010 Oct 1;70(14):1600–1607.
   Google Scholar
• Chatterjee P, Schweizer MT, Lucas JM, et al. Supraphysiological androgens suppress prostate cancer growth through androgen receptor-mediated DNA damage. J Clin Invest. 2019 Jul 16;129(10):4245–4260.
   Google Scholar
• Markowski MC, Kachhap S, De Marzo AM, et al. Molecular and clinical characterization of patients with metastatic castration resistant prostate cancer achieving deep responses to bipolar androgen therapy. Clin Genitourin Cancer. 2022 Apr;20(2):97–101.
   Google Scholar
• Schweizer M, Gulati R, Yezefski T, et al. 592P bipolar androgen therapy (BAT) plus olaparib in men with metastatic castration-resistant prostate cancer (mCRPC). Ann Oncol. 2021 [cited 2021 Sept 01];32:S639–S640.
   Google Scholar
• Markowski MC, Antonarakis ES. BRCA1 versus BRCA2 and PARP inhibitor sensitivity in prostate cancer: more different than alike? J Clin Oncol. 2020 Nov 10;38(32):3735–3739.
   Google Scholar
• Antonarakis ES, Wang H, Teply BA, et al. Interim results from a phase 2 study of olaparib (without ADT) in men with biochemically-recurrent prostate cancer after prostatectomy, with integrated biomarker analysis. J clin oncol. 2019;37(15_suppl):5045.
   Google Scholar
• Markowski MC, Wang H, Sullivan R, et al. Phase II trial of rucaparib (without ADT) in patients with metastatic hormone-sensitive prostate cancer harboring germline DNA repair gene mutations (TRIUMPH). J clin oncol. 2018;36(15_suppl): TPS5095–TPS5095.
   Google Scholar