PARPi Combos in Prostate Cancer
Novel PARP Inhibitor–Based Combinations Targeting Improved Patient Outcomes in Prostate Cancer

Released: April 12, 2021

Expiration: April 11, 2022

Charles Ryan
Charles Ryan, MD

Activity

Progress
1
Course Completed
References

  1. Friedlander TW, Pritchard CC, Beltran H. Personalizing therapy for metastatic prostate cancer: the role of solid and liquid tumor biopsies. Am Soc Clin Oncol Educ Book. 2017;37:358-369.
  2. Robinson D, Van Allen EM, Wu Y-M, et al. Integrative clinical genomics of advanced prostate cancer. Cell. 2015;161:1215-1228.
  3. Pritchard CC, Mateo J, Walsh MF, et al. Inherited DNA-repair gene mutations in men with metastatic prostate cancer. N Engl J Med. 2016;375:443-453.

     

  4. Olaparib [prescribing information]. Cambridge, UK: AstraZeneca; 2020.
  5. de Bono J, Mateo J, Fizazi K, et al. Olaparib for metastatic castration-resistant prostate cancer. N Engl J Med. 2020;382:2091-2102.
  6. ClinicalTrials.gov. Study of olaparib (Lynparza™) versus enzalutamide or abiraterone acetate in men with metastatic castration-resistant prostate cancer (PROfound Study). clinicaltrials.gov/ct2/show/NCT02987543. Accessed March 30, 2021.
  7. Hussain M, Mateo J, Fizazi K, et al. Survival with olaparib in metastatic castration-resistant prostate cancer. N Engl J Med. 2020; 383:2345-2357.
  8. Rucaparib [prescribing information]. Boulder, CO: Clovis Oncology; 2020.
  9. 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; 38:3763-3772.
  10. ClinicalTrials.gov. A study of rucaparib in patients with metastatic castration-resistant prostate cancer and homologous recombination gene deficiency (TRITON2). clinicaltrials.gov/ct2/show/NCT02952534. Accessed March 30, 2021.
  11. 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). Presented at: 2018 American Society of Clinical Oncology Genitourinary Cancers Symposium; February 8-10, 2018. Abstract TPS389.
  12. ClinicalTrials.gov. A study of rucaparib versus physician's choice of therapy in patients with metastatic castration-resistant prostate cancer and homologous recombination gene deficiency (TRITON3). clinicaltrials.gov/ct2/show/NCT02975934. Accessed March 30, 2021.
  13. de Bono JS, Mehra N, Higano CS, et al. TALAPRO-1: Phase II study of talazoparib (TALA) in patients (pts) with DNA damage repair alterations (DDRm) and metastatic castration-resistant prostate cancer (mCRPC). Presented at: 2021 American Society of Clinical Oncology Genitourinary Cancers Symposium; February 11-13, 2021. Abstract 93.
  14. ClinicalTrials.gov. A study of talazoparib in men with dna repair defects and metastatic castration-resistant prostate cancer. clinicaltrials.gov/ct2/show/NCT03148795. Accessed March 30, 2021.
  15. Abida W, Bryce AH, Vogelzang NJ, et al. Preliminary results from TRITON2: a phase 2 study of rucaparib in patients (pts) with metastatic castration-resistant prostate cancer (mCRPC) associated with homologous recombination repair (HRR) gene alterations. Presented at: 2018 European Society for Medical Oncology Congress. October 19-23, 2018. Abstract 3619.
  16. Lozano Mejorada R, Castro Marcos E, Aragon IM, et al. Clinical impact of somatic alterations in prostate cancer patients with and without previously known germline BRCA1/2 mutations: Results from PROREPAIR-A study. Presented at: 2020 European Society for Medical Oncology Virtual Congress; September 19-21, 2020. Abstract 612MO.
  17. 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;36:991-999.
  18. Polkinghorn WR, Parker JS, Lee MX, et al. Androgen receptor signaling regulates DNA repair in prostate cancers. Cancer Discov. 2013;3:1245-1253.
  19. Schiewer MJ, Goodwin JF, Han S, et al. Dual roles of PARP-1 promote cancer growth and progression. Cancer Discov. 2012;2:1134-1149.
  20. Asim M, Tarish F, Zecchini HI, et al. Synthetic lethality between androgen receptor signalling and the PARP pathway in prostate cancer. Nat Commun. 2017;8:374.
  21. 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;19:975-986.
  22. ClinicalTrials.gov. Ph II study to evaluate olaparib with abiraterone in treating metastatic castration resistant prostate cancer. clinicaltrials.gov/ct2/show/NCT01972217. Accessed March 30, 2021.
  23. ClinicalTrials.gov. Study on olaparib plus abiraterone as first-line therapy in men with metastatic castration-resistant prostate cancer. clinicaltrials.gov/ct2/show/NCT03732820. Accessed March 30, 2021.
  24. 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). Presented at: 2020 American Society of Clinical Oncology Annual Meeting; May 29-31, 2020. Abstract TPS5598.
  25. ClinicalTrials.gov. Talazoparib + enzalutamide vs. enzalutamide monotherapy in mCRPC (TALAPRO-2). clinicaltrials.gov/ct2/show/NCT03395197. Accessed March 30, 2021.
  26. ClinicalTrials.gov. A clinical study evaluating the benefit of adding rucaparib to enzalutamide for men with metastatic prostate cancer that has become resistant to testosterone-deprivation therapy (CASPAR). clinicaltrials.gov/ct2/show/NCT04455750. Accessed March 30, 2021.
  27. Rao A, Morris D, Assikis VJ, et al. Rucaparib plus enzalutamide in patients (pts) with metastatic castration-resistant prostate cancer (mCRPC): Pharmacokinetics (PK) and safety data from the phase Ib RAMP study. Presented at: 2021 American Society of Clinical Oncology Genitourinary Cancers Symposium; February 11-13, 2021. Abstract 79.
  28. ClinicalTrials.gov. Study of oral rucaparib with other anticancer agents in metastatic castration resistant prostate cancer patients (RAMP). clinicaltrials.gov/ct2/show/NCT04179396. Accessed March 30, 2021.
  29. Chi KN, Rathkopf DE, Attard G, et al. A phase III randomized, placebo-controlled, double-blind study of niraparib plus abiraterone acetate and prednisone versus abiraterone acetate and prednisone in patients with metastatic prostate cancer (MAGNITUDE). Presented at: 2020 American Society of Clinical Oncology Annual Meeting; May 29-31, 2020. Abstract TPS5588.
  30. ClinicalTrials.gov. A study of niraparib in combination with abiraterone acetate and prednisone versus abiraterone acetate and prednisone for treatment of participants with metastatic prostate cancer (MAGNITUDE). clinicaltrials.gov/ct2/show/NCT03748641. Accessed March 30, 2021.
  31. Vikas P, Borcherding N, Chennamadhavuni A, et al. Therapeutic potential of combining PARP inhibitor and immunotherapy in solid tumors. Front Oncol. 2020;10:570.
  32. Yu EY, Rodriguez JMMP, Gravis G, et al. Pembrolizumab (pembro) plus olaparib in patients (pts) with docetaxel-pretreated metastatic castration-resistant prostate cancer (mCRPC): KEYNOTE-365 cohort A efficacy, safety, and biomarker results. Presented at: 2020 American Society of Clinical Oncology Annual Meeting; May 29-31, 2020. Abstract 5544.
  33. Arranz Arija JA, Yu EY, Piulats JM, et al. Pembrolizumab (pembro) plus olaparib in patients (pts) with docetaxel-pretreated metastatic castration-resistant prostate cancer (mCRPC): KEYNOTE-365 Cohort A update. Presented at: 2020 European Society for Medical Oncology Virtual Congress; September 19-21, 2020. Abstract 621P.
  34. ClinicalTrials.gov. Study of pembrolizumab (MK-3475) combination therapies in metastatic castration-resistant prostate cancer (MK-3475-365/KEYNOTE-365). clinicaltrials.gov/ct2/show/NCT02861573. Accessed March 30, 2021.
  35. ClinicalTrials.gov. Study of pembrolizumab (MK-3475) plus olaparib versus abiraterone acetate or enzalutamide in metastatic castration-resistant prostate cancer (mCRPC) (MK-7339-010/KEYLYNK-010) (KEYLYNK-010 clinicaltrials.gov/ct2/show/NCT03834519. Accessed March 30, 2021.
  36. ClinicalTrials.gov. An investigational immunotherapy study of nivolumab in combination with rucaparib, docetaxel, or enzalutamide in metastatic castration-resistant prostate cancer (CheckMate 9KD). clinicaltrials.gov/ct2/show/NCT03338790. Accessed March 30, 2021.
  37. Alter R, Fleming GF, Stadler WM, et al. A phase Ib/IIa study of rucaparib (PARP inhibitor) combined with nivolumab in metastatic castrate-resistant prostate cancer and advanced/recurrent endometrial cancer. Presented at: 2019 American Society of Clinical Oncology Annual Meeting; May 31-June 4, 2019. Abstract TPS2663.
  38. ClinicalTrials.gov. Rucaparib and nivolumab in patients with prostate or endometrial cancer. clinicaltrials.gov/ct2/show/NCT03572478. Accessed March 30, 2021.
  39. 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;6:141.
  40. ClinicalTrials.gov. Phase I/II study of the anti-programmed death ligand-1 antibody MEDI4736 in combination with olaparib and/or cediranib for advanced solid tumors and advanced or recurrent ovarian, triple negative breast, lung, prostate and colorectal cancers. clinicaltrials.gov/ct2/show/NCT02484404. Accessed March 30, 2021.
  41. Schwarzenbach H, Gahan PB. Resistance to cis- and carboplatin initiated by epigenetic changes in ovarian cancer patients. Cancer Drug Resist. 2019;2:271-296.
  42. Schmid S, Omlin A, Higano C, et al. Activity of platinum-based chemotherapy in patients with advanced prostate cancer with and without DNA repair gene aberrations. JAMA Netw Open. 2020;3:e2021692.
  43. ClinicalTrials.gov. Docetaxel, carboplatin, and rucaparib camsylate in treating patients with metastatic castration resistant prostate cancer with homologous recombination DNA repair deficiency. clinicaltrials.gov/ct2/show/NCT03442556. Accessed March 30, 2021.
  44. Kelly WK, Leiby B, Einstein DJ, et al. Radium-223 (Rad) and niraparib (Nira) treatment (tx) in castrate-resistant prostate cancer (CRPC) patients (pts) with and without prior chemotherapy (chemo). Presented at: 2020 American Society of Clinical Oncology Annual Meeting; May 29-31, 2020. Abstract 5540.
  45. ClinicalTrials.gov. Phase IB trial of radium-223 and niraparib in patients with castrate resistant prostate cancer (NiraRad). clinicaltrials.gov/ct2/show/NCT03076203. Accessed March 30, 2021.
  46. Kaplan AR, Gueble S, Liu Y, et al. Cediranib suppresses homology-directed DNA repair through down-regulation of BRCA1/2 and RAD51. Sci Transl Med. 2019;11:eaav4508.
  47. Liu JF, Barry WT, Birrer M, et al. Overall survival and updated progression-free survival outcomes in a randomized phase II study of combination cediranib and olaparib versus olaparib in relapsed platinum-sensitive ovarian cancer. Ann Oncol. 2019;30:551-557.
  48. McKay RR, Radke MR, Shyr Y, et al. Biomarker analysis from a randomized phase II study of olaparib with or without cediranib in men with metastatic castration-resistant prostate cancer (mCRPC). Presented at: 2021 American Society of Clinical Oncology Genitourinary Cancers Symposium; February 11-13, 2021. Abstract 7.
  49. ClinicalTrials.gov. Olaparib with or without cediranib in treating patients with metastatic castration-resistant prostate cancer. clinicaltrials.gov/ct2/show/NCT02893917. Accessed March 30, 2021.
  50. ClinicalTrials.gov. Niraparib with standard combination radiation therapy and androgen deprivation therapy in treating patients with high risk prostate cancer (NADIR). clinicaltrials.gov/ct2/show/NCT04037254. Accessed March 30, 2021.