Enzalutamide versus Abiraterone Acetate as first-line treatment of castration resistant metastatic prostate cancer in geriatric (≥75) patients

Introduction: The efficacy and tolerability of Enzalutamide and Abiraterone Acetate have been reported in elderly patients with metastatic castration resistant prostate cancer (mCRPC). However, there is no randomized study directly comparing antitumor effects between these 2 agents in geriatric patients. We aimed to evaluate the efficacy of Enzalutamide (ENZA) and Abiraterone Acetate (AA) as a first-line treatment of mCRPC in elderly patients.

Materials and methods: The geriatric patients (≥75 years of age) with a diagnosis of mCRPC and treated with first-line ENZA or AA were included. The impacts of clinical parameters and treatment modalities on overall survival (mOS) were analyzed retrospectively and Cox regression analysis was performed.

Results: One hundred thirty-four mCRPC patients (77 in AA, 57 in ENZA), with a median age of 81 (75–93) were analyzed. The patient and disease characteristics were similar between arms. While there were more grade 1–2 toxicities in AA arm (45.5% vs 17.5%, P = 0.001), the discontinuation due to toxicity was similar between groups (8.5% vs 5.9%, P = 0.81). The mOS was 18.0 months (95% CI, 15.2–20.7) in AA, and 20.0 months (95% CI, 4.4–35.5) in ENZA arm (P = 0.47). In multivariate analysis, high Gleason score (≥8) (HR: 2.0 (95% CI, 1.1–3.4), P = 0.009) and high initial PSA values (≥100 ng/mL) (HR: 2.6 (95% CI, 1.5–4.8), P = 0.001) were poor prognostic factors. The choice of AA vs ENZA was insignificant as a predictor of OS (HR: 0.87 (95%CI, 0.48–1.56), P = 0.65).

Conclusion: In the first-line treatment of mCRPC in elderly (≥75) patients, AA and ENZA showed similar results in terms of mPFS and mOS. The clinical impacts of second-generation androgen receptor pathway inhibitors in the elderly population should be tested in prospective randomized studies.

Metastatic castration-resistant prostate cancer; Enzalutamide; Abiraterone Acetate; Elderly

[1] Ferlay J, Colombet M, Soerjomataram I, Dyba T, Randi G, Bettio M, et al. Cancer incidence and mortality patterns in Europe: estimates for 40 countries and 25 major cancers in 2018. European Journal of Cancer. 2018; 103: 356–387.

[2] Scosyrev E, Messing EM, Mohile S, Golijanin D, Wu G. Prostate cancer in the elderly: frequency of advanced disease at presentation and disease-specific mortality. Cancer. 2012; 118: 3062–3070.

[3] Pienta KJ, Bradley D. Mechanisms underlying the development of androgen-independent prostate cancer. Clinical Cancer Research. 2006; 12: 1665–1671.

[4] Scher HI, Halabi S, Tannock I, Morris M, Sternberg CN, Carducci MA, 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. Journal of Clinical Oncology. 2008; 26: 1148–1159.

[5] de Bono JS, Logothetis CJ, Molina A, Fizazi K, North S, Chu L, et al. Abiraterone and increased survival in metastatic prostate cancer. The New England Journal of Medicine. 2011; 364: 1995–2005.

[6] Ryan CJ, Smith MR, de Bono JS, Molina A, Logothetis CJ, de Souza P, et al. Abiraterone in metastatic prostate cancer without previous chemotherapy. The New England Journal of Medicine. 2013; 368: 138–148.

[7] Maines F, Caffo O, De Giorgi U, Fratino L, Lo Re G, Zagonel V, et al. Safety and clinical outcomes of Abiraterone Acetate after docetaxel in octogenarians with metastatic castration-resistant prostate cancer: results of the Italian compassionate use named patient programme. Clinical Genitourinary Cancer. 2016; 14: 48–55.

[8] Tran C, Ouk S, Clegg NJ, Chen Y, Watson PA, Arora V, et al. Development of a second-generation antiandrogen for treatment of advanced prostate cancer. Science. 2009; 324: 787–790.

[9] Beer TM, Armstrong AJ, Rathkopf DE, Loriot Y, Sternberg CN, Higano CS, et al. Enzalutamide in metastatic prostate cancer before chemotherapy. The New England Journal of Medicine. 2014; 371: 424–433.

[10] Scailteux LM, Campillo-Gimenez B, Kerbrat S, Despas F, Mathieu R, Vincendeau S, et al. Overall survival among chemotherapy-naive castration-resistant prostate cancer patients under abiraterone versus enzalutamide: a direct comparison based on a 2014-2018 French population study (the SPEAR cohort). American Journal of Epidemiology. 2021; 190: 413–422.

[11] Wang X, Hui Y, Wang S, Hu X, Yu X, Wang W, et al. Comparison of effectiveness and safety outcomes of abiraterone versus enzalutamide in patients with metastatic castration-resistant prostate cancer: a sys-tematic review and meta-analysis. Journal of Pharmaceutical Sciences. 2020; 23: 451–461.

[12] Balducci L. Studying cancer treatment in the elderly patient popula-tion. Cancer Control. 2014; 21: 215–220.

[13] Caffo O, Maines F, Rizzo M, Kinspergher S, Veccia A. Metastatic castration-resistant prostate cancer in very elderly patients: challenges and solutions. Clinical Interventions in Aging. 2017; 12: 19–28.

[14] Droz JP, Efstathiou E, Yildirim A, Cabrera P, Soo Kim C, Horchani A, et al. First-line treatment in senior adults with metastatic castration-resistant prostate cancer: a prospective international registry. Urologic Oncology. 2016; 34: 234 e221–239.

[15] 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. European Urology. 2009; 55: 1368–1375.

[16] Wallis CJD, Satkunasivam R, Saskin R, Bansal S, Kulkarni GS, Emmenegger U, et al. Population-based analysis of treatment toxicity among men with castration-resistant prostate cancer: a phase IV study. Urology. 2018; 113: 138–145.

[17] Beer TM, Armstrong AJ, Rathkopf D, Loriot Y, Sternberg CN, Higano CS, et al. Enzalutamide in men with chemotherapy-naive metastatic castration-resistant prostate cancer: extended analysis of the phase 3 PREVAIL study. European Urology. 2017; 71: 151–154.

[18] Izumi K, Mizokami A, Namiki M, Inoue S, Tanaka N, Yoshio Y, et al. Enzalutamide versus abiraterone as a first-line endocrine therapy for castration-resistant prostate cancer (ENABLE study for PCa): a study protocol for a multicenter randomized phase III trial. BMC Cancer. 2017; 17: 677.

[19] Hara I, Yamashita S, Nishizawa S, Kikkawa K, Shimokawa T, Kohjimoto Y. Enzalutamide versus abiraterone as a first-line en-docrine therapy for castration-resistant prostate cancer: protocol for a multicenter randomized phase 3 trial. JMIR Research Protocols. 2018; 7: e11191.

[20] Shore ND, Saltzstein D, Sieber P, Mehlhaff B, Gervasi L, Phillips J, et al. Results of a real-world study of enzalutamide and abiraterone acetate with prednisone tolerability (REAAcT). Clinical Genitourinary Cancer. 2019; 17: 457–463.e456.

[21] Thiery-Vuillemin A, Hvid Poulsen M, Lagneau E, Ploussard G, Birtle A, Dourthe LM, et al. Impact of abiraterone acetate plus prednisone or enzalutamide on patient-reported outcomes in patients with metastatic castration-resistant prostate cancer: final 12-mo analysis from the observational AQUARiUS study. European Urology. 2020; 77: 380–387.

[22] Khalaf DJ, Sunderland K, Eigl BJ, Kollmannsberger CK, Ivanov N, Finch DL, et al. Health-related quality of life for abiraterone plus prednisone versus enzalutamide in patients with metastatic castration-resistant prostate cancer: results from a phase II randomized trial. European Urology. 2019; 75: 940–947.