Managing lines of therapy in castration-resistant prostate cancer: real-life snapshot from a multicenter cohort
To provide a snapshot of toxicities and oncologic outcomes of Abiraterone (AA) and Enzalutamide (EZ) in a chemo-naïve metastatic castration-resistant prostate cancer (mCPRC) population from a longitudinal real-life multicenter cohort.
We prospectively collected data on chemo-naïve mCRPC patients treated with AA or EZ. Primary outcomes were PSA response, oncologic outcomes and toxicity profile. The Kaplan–Meier method was used to compare differences in terms of progression-free survival (PFS) between AA vs EZ and high- vs low-volume disease cohorts. Univariable and multivariable Cox regression analyses were performed to identify predictors of PFS. Toxicity, PSA response rates and oncologic outcomes on second line were compared with those observed on first line.
Out of 137 patients, 88 received AA, and 49 EZ. On first line, patients receiving EZ had significantly higher PSA response compared with AA (95.9% vs 67%, p < 0.001), comparable toxicity rate (10.2% vs 16.3%, p = 0.437) and PFS probabilities (p = 0.145). Baseline PSA and high-volume disease were predictors of lower PFS probabilities at univariable analysis (p = 0.027 and p = 0.007, respectively). Overall, 28 patients shifted to a second-line therapy (EZ or radiometabolic therapy). Toxicity and PSA response rates on second line were comparable to those observed on first line (11.1% vs 12.4%, p = 0.77; 73.1% vs 77.4%, p = 0.62, respectively); 2-year PFS, cancer-specific and overall survival probabilities were comparable to those displayed in first-line cohort (12.1% vs 16.2%, p = 0.07; 85.7% vs 86.4%, p = 0.98; 71% vs 80.3%, p = 0.66, respectively).
Toxicity profile, PSA response rate and oncological outcomes were comparable between first-line and second-line courses in patients treated with either AA or EZ for mCRPC. Our findings showed the tolerability and oncological effectiveness, when feasible, of two lines of therapy other than chemotherapy.
keywordsCastration-resistant prostate cancer Metastatic disease Systemic therapy High volume disease Androgen receptor targeted agent
Castration-resistant prostate cancer
Hormone-sensitive metastatic prostate cancer
Metastatic castration-resistant prostate cancer
Androgen deprivation therapy
Non-metastatic castration-resistant prostate cancer
Food and drug administration
Androgen receptor-targeted agents
MF: project development, data collection, data analysis, manuscript writing; RM: data collection, data analysis; CN: data collection; LC: data collection, data analysis, manuscript editing; FC: data collection; GT: data collection; CL: data collection; RSF: data collection; GT: data collection; UA: data collection; AB: data collection; SG: data collection; SG: data collection; JG: data collection; LS: data collection; AT: data collection; MG: project development, data analysis; GS: project development, data analysis, manuscript writing, manuscript editing
Compliance with ethical standards
All patients have signed the informed consent for data collection and follow-up.
- 2.Ryan CJ, Smith MR, Fizazi K, Saad F, Mulders PF, Sternberg CN et al (2015) Abiraterone acetate plus prednisone versus placebo plus prednisone in chemotherapy-naive men with metastatic castration-resistant prostate cancer (COU-AA-302): final overall survival analysis of a randomised, doubleblind, placebo-controlled phase 3 study. Lancet Oncol 16:152–160CrossRefGoogle Scholar
- 3.De Nunzio C, Presicce F, Giacinti S, Bassanelli M, Tubaro A (2018) Castration-resistance prostate cancer: what is in the pipeline? Minerva Urol Nefrol 70(1):22–41Google Scholar
- 4.National Comprehensive Cancer Network: NCCN Clinical Practice Guidelines in Oncology: Prostate Cancer (Version 4.2018). http://www.nccn.org/professionals/physician_gls/pdf/prostate.pdf. Accessed 29 Jan 2019
- 10.Common terminology criteria for adverse events (CTCAE) v4.02. https://evs.nci.nih.gov/ftp1/CTCAE/CTCAE_4.03/Archive/CTCAE_4.02_2009-09-15_QuickReference_8.5x11.pdf. Accessed 29 Jan 2019
- 16.Mottet N, Bellmunt J, Briers E, Bolla M, Bourke L, Cancer EEESGoP. EAU–ESTRO–ESUR–SIOG guidelines on prostate cancer. In: Office EG, editor. https://uroweb.org/guideline/prostate-cancer/2018. Accessed 30 Jan 2019
- 19.Buelens S, De Bleser E, Dhondt B, Verla W, Decaestecker K, Ost P et al (2018) Importance of metastatic volume in prognostic models to predict survival in newly diagnosed metastatic prostate cancer. World J Urol 2018:1–7Google Scholar
- 23.James ND, Sydes MR, Clarke NW, Mason MD, Dearnaley DP, Spears MR et al (2016) Addition of docetaxel, zoledronic acid, or both to first-line long-term hormone therapy in prostate cancer (STAMPEDE): survival results from an adaptive, multiarm, multistage, platform randomised controlled trial. Lancet 387(10024):1163–1177CrossRefGoogle Scholar
- 24.Oh WK, Cheng WY, Miao R, Vekeman F, Gauthier-Loiselle M, Duh MS et al (2018) Real-world outcomes in patients with metastatic castration resistant prostate cancer receiving second line chemotherapy versus an alternative androgen receptor targeted agent (ARTA) following early progression on a first-line ARTA in a US community oncology setting. Urol Oncol 36(11):500.e1–500.e9CrossRefGoogle Scholar
- 25.Matsubara N, Yamada Y, Tabata KI, Satoh T, Kamiya N, Suzuki H et al (2017) Comparison of sequential treatment with androgen receptortargeted agent followed by another androgen receptor-targeted agent versus androgen receptor targeted agent followed by docetaxel in chemotherapy naïve patients with metastatic castration-resistant prostate cancer. Clin Genitourin Cancer 15(6):e1073–e1080CrossRefGoogle Scholar