Continuing enzalutamide with docetaxel in castration-resistant prostate cancer.

Abstract

In metastatic prostate cancer, several life-prolonging therapeutics, such as novel androgen receptor pathway inhibitors, abiraterone acetate and second-generation antiandrogens, and the chemotherapeutic agent docetaxel, are available for both metastatic castration-sensitive prostate cancer and metastatic castration-resistant prostate cancer (mCRPC). Similarly, cabazitaxel, radioisotopes, and poly(ADP-ribose) polymerase inhibitors are available for the treatment of mCRPC. There is currently no evidence of a survival benefit of combination therapy in mCRPC, and life-prolonging drugs are administered sequentially for patients with mCRPC. However, the potential ability of combination therapy to delay progression has been shown in the CHEIRON (adding enzalutamide to docetaxel), 1 Caffo O Ortega C Nolè F et al. Docetaxel and prednisone with or without enzalutamide as first-line treatment in patients with metastatic castration-resistant prostate cancer: CHEIRON, a randomised phase II trial. Eur J Cancer. 2021; 155: 56-63 Summary Full Text Full Text PDF PubMed Scopus (4) Google Scholar ACIS (adding apalutamide to abiraterone plus prednisone), 2 Saad F Efstathiou E Attard G et al. Apalutamide plus abiraterone acetate and prednisone versus placebo plus abiraterone and prednisone in metastatic, castration-resistant prostate cancer (ACIS): a randomised, placebo-controlled, double-blind, multinational, phase 3 study. Lancet Oncol. 2021; 22: 1541-1559 Summary Full Text Full Text PDF PubMed Scopus (18) Google Scholar IPATential150 (adding ipatasertib to abiraterone plus prednisone or prednisolone), 3 Sweeney C Bracarda S Sternberg CN et al. Ipatasertib plus abiraterone and prednisolone in metastatic castration-resistant prostate cancer (IPATential150): a multicentre, randomised, double-blind, phase 3 trial. Lancet. 2021; 398: 131-142 Summary Full Text Full Text PDF PubMed Scopus (60) Google Scholar and PROpel (adding olaparib to abiraterone plus prednisone or prednisolone) trials. 4 Saad F Armstrong AJ Thiery-Vuillemin A 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). Proc Am Soc Clin Oncol. 2022; 40: 11 Crossref Google Scholar Additionally, the survival benefit of combinations of androgen receptor pathway inhibitors, including the addition of abiraterone or the second-generation antiandrogen darolutamide to castration plus docetaxel, was shown in the PEACE-1 (adding abiraterone plus prednisone to docetaxel) 5 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 × 2 factorial design. Lancet. 2022; 399: 1695-1707 Summary Full Text Full Text PDF PubMed Scopus (52) Google Scholar and ARASENS (adding darolutamide to docetaxel) trials. 6 Smith MR Hussain M Saad F et al. Darolutamide and survival in metastatic, hormone-sensitive prostate cancer. N Engl J Med. 2022; 386: 1132-1142 Crossref PubMed Scopus (80) Google Scholar Continuous enzalutamide after progression of metastatic castration-resistant prostate cancer treated with docetaxel (PRESIDE): an international, randomised, phase 3b studyPRESIDE met its primary endpoint and showed that continuing enzalutamide with docetaxel plus androgen deprivation therapy delayed time to progression compared with docetaxel plus androgen deprivation therapy alone, supporting the hypothesis that enzalutamide maintenance could control persistent androgen-dependent clones in men with mCRPC who progress after treatment with enzalutamide alone. Full-Text PDF