In questo podcast parleremo della tossicità e gestione dei nuovi farmaci per il trattamento del tumore della prostata, con particolare focus sui PARP inibitori. Questi rappresentano una delle terapie target più promettenti introdotte nella pratica clinica dal 2020 per il tumore prostatico metastatico resistente alla castrazione (CRPC), sia come singoli agenti sia in combinazione con gli ARSI.



Bibliografia
  1. Abida W, 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. Clinical Cancer Research 2020; 26, 2487–2496.
  2. Abida W, et al. Rucaparib in Men With Metastatic Castration-Resistant Prostate Cancer Harboring a BRCA1 or BRCA2 Gene Alteration. JCO 2020; 38, 3763–3772.
  3. Agarwal N, et al2022. Talapro-3: A phase 3, double-blind, randomized study of enzalutamide (ENZA) plus talazoparib (TALA) versus placebo plus enza in patients with DDR gene mutated metastatic castration-sensitive prostate cancer (mCSPC). JCO 40, TPS221–TPS221.
  4. Carreira S, et al. Biomarkers Associating with PARP Inhibitor Benefit in Prostate Cancer in the TOPARP-B Trial. Cancer Discovery 2021; 11, 2812–2827.
  5. Chi K, 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. JCO 2022; 40, 12–12.
  6. Chi KN, et al. Niraparib plus abiraterone acetate with prednisone in patients with metastatic castration-resistant prostate cancer and homologous recombination repair gene alterations: second interim analysis of the randomized phase III MAGNITUDE trial. Annals of Oncology 2023; 34, 772–782.
  7. Clarke N, et al. Olaparib combined with abiraterone in patients with metastatic castration-resistant prostate cancer: a randomised, double-blind, placebo-controlled, phase 2 trial. The Lancet Oncology 2018; 19, 975–986.
  8. Clarke NW, et al. 2022. Abiraterone and Olaparib for Metastatic Castration-Resistant Prostate Cancer. NEJM Evidence 2022; 1.
  9. de Bono J, et al. Olaparib for Metastatic Castration-Resistant Prostate Cancer. N Engl J Med 2020; 382, 2091–2102.
  10. de Bono JS, et al. Talazoparib monotherapy in metastatic castration-resistant prostate cancer with DNA repair alterations (TALAPRO-1): an open-label, phase 2 trial. The Lancet Oncology 2021; 22, 1250–1264.
  11. Hussain M, et al. Survival with Olaparib in Metastatic Castration-Resistant Prostate Cancer. N Engl J Med 2020; 383, 2345–2357.
  12. Hussain MHA, et al. BRCAAWAY: A randomized phase 2 trial of abiraterone, olaparib, or abiraterone + olaparib in patients with metastatic castration-resistant prostate cancer (mCRPC) with DNA repair defects. JCO 2022; 40, 5018–5018.
  13. Loehr A, et al. Response to Rucaparib in BRCA-Mutant Metastatic Castration-Resistant Prostate Cancer Identified by Genomic Testing in the TRITON2 Study. Clinical Cancer Research 2021; 27, 6677–6686.
  14. Lozano Mejorada R, et al. 612MO Clinical impact of somatic alterations in prostate cancer patients with and without previously known germline BRCA1/2 mutations: Results from PROREPAIR-A study. Annals of Oncology 2020; 31, S509–S510.
  15. Lozano R, et al. PROREPAIR-A: Clinical and molecular characterization study of prostate cancer (PC) patients with and without previously known germline BRCA1/2 mutations. JCO 2020; 38, 5511–5511.
  16. Mateo J, et al. DNA-Repair Defects and Olaparib in Metastatic Prostate Cancer. N Engl J Med 2015; 373, 1697–1708.
  17. Mateo J, 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; 21, 162–174.
  18. Rao A, et al. CASPAR (Alliance A031902): A randomized, phase III trial of enzalutamide (ENZ) with rucaparib (RUCA)/placebo (PBO) as a novel therapy in first-line metastatic castration-resistant prostate cancer (mCRPC). JCO 2021; 39, TPS181–TPS181.
  19. Rathkopf DE, et al. AMPLITUDE: A study of niraparib in combination with abiraterone acetate plus prednisone (AAP) versus AAP for the treatment of patients with deleterious germline or somatic homologous recombination repair (HRR) gene-altered metastatic castration-sensitive prostate cancer (mCSPC). JCO 2021; 39, TPS176–TPS176.
  20. Saad F, et al. PROpel: Phase III trial of olaparib (ola) and abiraterone (abi) versus placebo (pbo) and abi as first-line (1L) therapy for patients (pts) with metastatic castration-resistant prostate cancer (mCRPC). JCO 2022; 40, 11–11.
  21. Saad, F, et al. Interim results of a phase Ib study of niraparib plus androgen receptor-targeted therapy in men with metastatic castration-resistant prostate cancer. Annals of Oncology. 2018; 29, viii292.
  22. Saad F, et al, 2023. Olaparib plus abiraterone versus placebo plus abiraterone in metastatic castration-resistant prostate cancer (PROpel): final prespecified overall survival results of a randomised, double-blind, phase 3 trial. The Lancet Oncology 24, 1094–1108.
  23. Saad F, et al. Patient-reported outcomes with olaparib plus abiraterone versus placebo plus abiraterone for metastatic castration-resistant prostate cancer: a randomised, double-blind, phase 2 trial. The Lancet Oncology 2022.
  24. Smith MR, et al. Niraparib in patients with metastatic castration-resistant prostate cancer and DNA repair gene defects (GALAHAD): a multicentre, open-label, phase 2 trial. The Lancet Oncology 2022; 23, 362–373.