Enzalutamide versus Abiraterone Acetate as ﬁrst-line treatment of castration resistant metastatic prostate cancer in geriatric (≥75) patients
1Muğla Sıtkı Koçman University School of Medicine, Medical Oncology, 48000 Muğla, Turkey
2Dokuz Eylül University School of Medicine, Medical Oncology, 35220 İzmir, Turkey
3Ankara University School of Medicine, Medical Oncology, 06560 Ankara Turkey
4Dr. Abdurrahman Yurtarslan Research and Training Hospital, Medical Oncology, 06200 Ankara, Turkey
5Pamukkale University School of Medicine, Medical Oncology, 20160 Denizli, Turkey
6Marmara University School of Medicine, Medical Oncology, 34722 İstanbul, Turkey
7Selçuk University School of Medicine, Medical Oncology, 42250 Konya, Turkey
8Bahçeşehir University School of Medicine, İstanbul and Medical Park İzmir Hospital, Medical Oncology, 34488 İzmir, Turkey
9Atatürk Chest Disease and Chest Surgery Research and Training Hospital, Department of Medical Oncology, 06280 Ankara, Turkey
10Akdeniz University School of Medicine, Medical Oncology, 07070 Antalya, Turkey
11Afyon Kocatepe University School of Medicine, Medical Oncology, 03200 Afyon, Turkey
12Trakya University School of Medicine, Medical Oncology, 22030 Edirne, Turkey
13Gülhane Research and Training Hospital, Medical Oncology, 06010 Ankara, Turkey
14Erciyes University School of Medicine, Medical Oncology, 38280 Kayseri, Turkey
15Kütahya Health Science University, Evliya Çelebi Research and Training Hospital, Medical Oncology, 43100 Kütahya, Turkey
16Muğla Sıtkı Koçman University School of Medicine, Radiation Oncology, 48000 Muğla, Turkey
17Muğla Sıtkı Koçman University School of Medicine, Internal Medicine, 48000 Muğla, Turkey
18Yıldırım Beyazıt University, Atatürk Research and Training Hospital, Medical Oncology, 06760 Ankara, Turkey
Submitted: 18 January 2021 Accepted: 02 March 2021
Online publish date: 02 June 2021
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
Ali Alkan,Zeynep Gülsüm Güç,Mustafa Gürbüz,Güliz Özgün,Serkan Değirmencioğlu,Mutlu Doğan,Tuğba Akın Telli,Özge Keskin,Çağatay Arslan,Burak Bilgin,Sema Sezgin Göksu,Hacer Demir,Elif Berna Köksoy,Osman Köstek,İsmail Ertürk,Teoman Şakalar,Arzu Yaşar,Görkem Türkkan,Büşra Kasım,Aziz Karaoğlu,Berna Çakmak Öksüzoğlu,Fulden Yumuk,Mehmet Ali Şendur,Hasan Şenol Coşkun,İrfan Çiçin,Nuri Karadurmuş,Özgür Tanrıverdi,Hakan Akbulut,Yüksel Ürün. Enzalutamide versus Abiraterone Acetate as ﬁrst-line treatment of castration resistant metastatic prostate cancer in geriatric (≥75) patients. Journal of Men's Health. 2021.doi:10.31083/jomh.2021.041.
 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.
 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.
 Pienta KJ, Bradley D. Mechanisms underlying the development of androgen-independent prostate cancer. Clinical Cancer Research. 2006; 12: 1665–1671.
 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.
 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.
 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.
 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.
 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.
 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.
 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.
 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.
 Balducci L. Studying cancer treatment in the elderly patient popula-tion. Cancer Control. 2014; 21: 215–220.
 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.
 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.
 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.
 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.
 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.
 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.
 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.
 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.
 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.
 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.
Science Citation Index Expanded Created as SCI in 1964, Science Citation Index Expanded now indexes over 9,200 of the world’s most impactful journals across 178 scientific disciplines. More than 53 million records and 1.18 billion cited references date back from 1900 to present.
Social Sciences Citation Index Social Sciences Citation Index contains over 3,400 journals across 58 social sciences disciplines, as well as selected items from 3,500 of the world’s leading scientific and technical journals. More than 9.37 million records and 122 million cited references date back from 1900 to present.
Current Contents - Social & Behavioral Sciences Current Contents - Social & Behavioral Sciences provides easy access to complete tables of contents, abstracts, bibliographic information and all other significant items in recently published issues from over 1,000 leading journals in the social and behavioral sciences.
Current Contents - Clinical Medicine Current Contents - Clinical Medicine provides easy access to complete tables of contents, abstracts, bibliographic information and all other significant items in recently published issues from over 1,000 leading journals in clinical medicine.
SCOPUS Scopus is Elsevier's abstract and citation database launched in 2004. Scopus covers nearly 36,377 titles (22,794 active titles and 13,583 Inactive titles) from approximately 11,678 publishers, of which 34,346 are peer-reviewed journals in top-level subject fields: life sciences, social sciences, physical sciences and health sciences.
DOAJ DOAJ is a community-curated online directory that indexes and provides access to high quality, open access, peer-reviewed journals.
CrossRef Crossref makes research outputs easy to find, cite, link, assess, and reuse. Crossref committed to open scholarly infrastructure and collaboration, this is now announcing a very deliberate path.
Portico Portico is a community-supported preservation archive that safeguards access to e-journals, e-books, and digital collections. Our unique, trusted process ensures that the content we preserve will remain accessible and usable for researchers, scholars, and students in the future.