nach oben

Clinical and Translational Oncology

Erschienen in:

15.10.2019 | Research Article

Role of novel hormonal therapies in the management of non-metastatic castration-resistant prostate cancer: a literature-based meta-analysis of randomized trials

verfasst von: G. Roviello, M. R. Gatta Michelet, A. D’Angelo, S. Nobili, E. Mini

Erschienen in: Clinical and Translational Oncology | Ausgabe 7/2020

Einloggen, um Zugang zu erhalten

Abstract

Background

Novel hormonal therapies have been recently investigated in non-metastatic castration-resistant prostate cancer (CRPC). We performed a meta-analysis to assess the efficacy and safety of novel hormonal therapies in non-metastatic CRPC.

Materials and methods

The primary outcome was metastasis-free survival (MFS). The secondary endpoints were overall survival (OS), time to PSA progression and safety. We planned a subgroup analysis according to the PSA doubling time (> 6 vs < 6 months), Eastern Cooperative Oncology Group (ECOG) performance status (1 vs 0) and concomitant use of bone-targeting agent (yes vs no).

Results

Pooled analysis of novel hormonal therapies revealed significantly increased MFS compared with placebo (hazard ratio (HR): HR = 0.32, 95% CI 0.25–0.41; p < 0.00001). The subgroup analysis showed a statistically significant MFS advantage in favour of men with the lower ECOG performance status. Other secondary endpoints favoured the novel hormonal therapies. The relative risk (RR) of grade ≥ 3 adverse events and ≥ 3 hypertension was 1.31 and 1.39, respectively.

Conclusions

This study confirmed the efficacy and safety of the novel hormonal therapies in non-metastatic CRPC.

Nur mit Berechtigung zugänglich

Siegel RL, Miller KD, Jemal A. Cancer statistics, 2018. CA Cancer J Clin Am Cancer Soc. 2018;68:7–30. https://doi.org/10.3322/caac.21442.CrossRef

Mottet N, Bellmunt J, Bolla M, Briers E, Cumberbatch MG, De Santis M, et al. EAU-ESTRO-SIOG guidelines on prostate cancer. Part 1: screening, diagnosis, and local treatment with curative intent. Eur Urol. 2017;71:618–29. https://doi.org/10.1016/j.eururo.2016.08.003.CrossRefPubMed

Neppl-Huber C, Zappa M, Coebergh JW, Rapiti E, Rachtan J, Holleczek B, et al. Changes in incidence, survival and mortality of prostate cancer in Europe and the United States in the PSA era: additional diagnoses and avoided deaths. Ann Oncol Off J Eur Soc Med Oncol. 2012;23:1325–34. https://doi.org/10.1093/annonc/mdr414.CrossRef

Anantharaman A, Small EJ. Tackling non-metastatic castration-resistant prostate cancer: special considerations in treatment. Expert Rev Anticancer Ther. 2017;17:625–33. https://doi.org/10.1080/14737140.2017.1333903.CrossRefPubMed

Smith MR, Kabbinavar F, Saad F, Hussain A, Gittelman MC, Bilhartz DL, et al. Natural history of rising serum prostate-specific antigen in men with castrate nonmetastatic prostate cancer. J Clin Oncol. 2005;23:2918–25. https://doi.org/10.1200/JCO.2005.01.529.CrossRefPubMed

Taplin M-E, Balk SP. Androgen receptor: a key molecule in the progression of prostate cancer to hormone independence. J Cell Biochem. 2004;91:483–90. https://doi.org/10.1002/jcb.10653.CrossRefPubMed

Coleman RE. Clinical features of metastatic bone disease and risk of skeletal morbidity. Clin Cancer Res. 6249s;12:6243s–9s. https://doi.org/10.1158/1078-0432.CCR-06-0931.CrossRefPubMed

Freedland SJ, Richhariya A, Wang H, Chung K, Shore ND. Treatment patterns in patients with prostate cancer and bone metastasis among US community-based urology group practices. Urology. 2012;80:293–8. https://doi.org/10.1016/j.urology.2012.04.007.CrossRefPubMed

Smith MR, Cook R, Lee K-A, Nelson JB. Disease and host characteristics as predictors of time to first bone metastasis and death in men with progressive castration-resistant nonmetastatic prostate cancer. Cancer. 2011;117:2077–85. https://doi.org/10.1002/cncr.25762.CrossRefPubMed

10.

Smith MR, Saad F, Oudard S, Shore N, Fizazi K, Sieber P, et al. Denosumab and bone metastasis-free survival in men with nonmetastatic castration-resistant prostate cancer: exploratory analyses by baseline prostate-specific antigen doubling time. J Clin Oncol. 2013;31:3800–6. https://doi.org/10.1200/JCO.2012.44.6716.CrossRefPubMedPubMedCentral

11.

Horwich A, Hugosson J, de Reijke T, Wiegel T, Fizazi K, Kataja V, et al. Prostate cancer: ESMO consensus conference guidelines 2012. Ann Oncol Off J Eur Soc Med Oncol. 2013;24:1141–62. https://doi.org/10.1093/annonc/mds624.CrossRef

12.

Scher HI, Liebertz C, Kelly WK, Mazumdar M, Brett C, Schwartz L, et al. Bicalutamide for advanced prostate cancer: the natural versus treated history of disease. J Clin Oncol. 1997;15:2928–38. https://doi.org/10.1200/JCO.1997.15.8.2928.CrossRefPubMed

13.

Lodde M, Lacombe L, Fradet Y. Salvage therapy with bicalutamide 150 mg in nonmetastatic castration-resistant prostate cancer. Urology. 2010;76:1189–93. https://doi.org/10.1016/j.urology.2009.12.057.CrossRefPubMed

14.

Suzuki H, Okihara K, Miyake H, Fujisawa M, Miyoshi S, Matsumoto T, et al. Alternative nonsteroidal antiandrogen therapy for advanced prostate cancer that relapsed after initial maximum androgen blockade. J Urol. 2008;180:921–7. https://doi.org/10.1016/j.juro.2008.05.045.CrossRefPubMed

15.

Mason MD, Sydes MR, Glaholm J, Langley RE, Huddart RA, Sokal M, et al. Oral sodium clodronate for nonmetastatic prostate cancer—results of a randomized double-blind placebo-controlled trial: Medical Research Council PR04 (ISRCTN61384873). J Natl Cancer Inst. 2007;99:765–76. https://doi.org/10.1093/jnci/djk178.CrossRefPubMed

16.

Nelson JB, Love W, Chin JL, Saad F, Schulman CC, Sleep DJ, et al. Phase 3, randomized, controlled trial of atrasentan in patients with nonmetastatic, hormone-refractory prostate cancer. Cancer. 2008;113:2478–87. https://doi.org/10.1002/cncr.23864.CrossRefPubMed

17.

Esther J, Maughan BL, Anderson N, Agarwal N, Hahn AW. Management of nonmetastatic castration-resistant prostate cancer: recent advances and future direction. Curr Treat Options Oncol. 2019;20:14. https://doi.org/10.1007/s11864-019-0611-z.CrossRefPubMed

18.

Smith MR, Saad F, Coleman R, Shore N, Fizazi K, Tombal B, et al. Denosumab and bone-metastasis-free survival in men with castration-resistant prostate cancer: results of a phase 3, randomised, placebo-controlled trial. Lancet (London, England). 2012;379:39–46. https://doi.org/10.1016/S0140-6736(11)61226-9.CrossRef

19.

Smith MR, Saad F, Chowdhury S, Oudard S, Hadaschik BA, Graff JN, et al. Apalutamide treatment and metastasis-free survival in prostate cancer. N Engl J Med. 2018;378:1408–18. https://doi.org/10.1056/NEJMoa1715546.CrossRefPubMed

20.

Hussain M, Fizazi K, Saad F, Rathenborg P, Shore N, Ferreira U, et al. Enzalutamide in men with nonmetastatic, castration-resistant prostate cancer. N Engl J Med. 2018;378:2465–74. https://doi.org/10.1056/NEJMoa1800536.CrossRefPubMedPubMedCentral

21.

Fizazi K, Shore N, Tammela TL, Ulys A, Vjaters E, Polyakov S, et al. Darolutamide in nonmetastatic, castration-resistant prostate cancer. N Engl J Med. 2019;380:1235–46. https://doi.org/10.1056/NEJMoa1815671.CrossRefPubMed

22.

Moher D, Shamseer L, Clarke M, Ghersi D, Liberati A, Petticrew M, et al. Preferred reporting items for systematic review and meta-analysis protocols (PRISMA-P) 2015 statement. Syst Rev. 2015;4:1. https://doi.org/10.1186/2046-4053-4-1.CrossRefPubMedPubMedCentral

23.

Jadad AR, Moore RA, Carroll D, Jenkinson C, Reynolds DJ, Gavaghan DJ, et al. Assessing the quality of reports of randomized clinical trials: is blinding necessary? Control Clin Trials. 1996;17:1–12. https://www.ncbi.nlm.nih.gov/pubmed/8721797.CrossRefPubMed

24.

DerSimonian R, Laird N. Meta-analysis in clinical trials. Control Clin Trials. 1986;7:177–88. https://www.ncbi.nlm.nih.gov/pubmed/3802833.CrossRefPubMed

25.

Cochran WG. The combination of estimates from different experiments. Biometrics. 1954;10:101. https://doi.org/10.2307/3001666.CrossRef

26.

Higgins JPT, Thompson SG, Deeks JJ, Altman DG. Measuring inconsistency in meta-analyses. BMJ. 2003;327:557–60. https://doi.org/10.1136/bmj.327.7414.557.CrossRefPubMedPubMedCentral

27.

Roviello G, Sigala S, Sandhu S, Bonetta A, Cappelletti MR, Zanotti L, et al. Role of the novel generation of androgen receptor pathway targeted agents in the management of castration-resistant prostate cancer: a literature based meta-analysis of randomized trials. Eur J Cancer. 2016;61:111–21. https://doi.org/10.1016/j.ejca.2016.04.002.CrossRefPubMed

28.

Francini E, Petrioli R, Roviello G. No clear evidence of a clinical benefit of a sequential therapy regimen with abiraterone acetate and enzalutamide. Expert Rev Anticancer Ther. 2014;14:1135–40. https://doi.org/10.1586/14737140.2014.949677.CrossRefPubMed

29.

Petrioli R, Francini E, Roviello G. Is there still a place for docetaxel rechallenge in prostate cancer? World J Clin Oncol. 2015;6:99. https://doi.org/10.5306/wjco.v6.i5.99.CrossRefPubMedPubMedCentral

30.

Afshar M, Evison F, James ND, Patel P. Shifting paradigms in the estimation of survival for castration-resistant prostate cancer: a tertiary academic center experience. Urol Oncol. 2015;33(338):e1–7. https://doi.org/10.1016/j.urolonc.2015.05.003.CrossRef

31.

Xie W, Regan MM, Buyse M, Halabi S, Kantoff PW, Sartor O, et al. Metastasis-free survival is a strong surrogate of overall survival in localized prostate cancer. J Clin Oncol. 2017;35:3097–104. https://doi.org/10.1200/JCO.2017.73.9987.CrossRefPubMedPubMedCentral

32.

Roviello G, Generali D. Is the fatigue an adverse event of the second generation of hormonal therapy? Data from a literature-based meta-analysis. Med Oncol. 2018;35:29. https://doi.org/10.1007/s12032-018-1081-z.CrossRefPubMed

33.

Iacovelli R, Verri E, Cossu Rocca M, Aurilio G, Cullurà D, De Cobelli O, et al. The incidence and relative risk of cardiovascular toxicity in patients treated with new hormonal agents for castration-resistant prostate cancer. Eur J Cancer. 2015;51:1970–7. https://doi.org/10.1016/j.ejca.2015.06.106.CrossRefPubMed

34.

Di Nunno V, Mollica V, Santoni M, Gatto L, Schiavina R, Fiorentino M, et al. New hormonal agents in patients with nonmetastatic castration-resistant prostate cancer: meta-analysis of efficacy and safety outcomes. Clin Genitourin Cancer. 2019. https://doi.org/10.1016/j.clgc.2019.07.001.CrossRefPubMed

Titel: Role of novel hormonal therapies in the management of non-metastatic castration-resistant prostate cancer: a literature-based meta-analysis of randomized trials
verfasst von: G. Roviello
M. R. Gatta Michelet
A. D’Angelo
S. Nobili
E. Mini
Publikationsdatum: 15.10.2019
Verlag: Springer International Publishing
Erschienen in: Clinical and Translational Oncology / Ausgabe 7/2020
Print ISSN: 1699-048X
Elektronische ISSN: 1699-3055
DOI: https://doi.org/10.1007/s12094-019-02228-2

Neu im Fachgebiet Onkologie

18.04.2024 | Wirbelsäulenmetastase | Nachrichten

Live-Webinar: Aktuelle Leitlinien bei Herz-Kreislauf-Erkrankungen

Springer Medizin

Role of novel hormonal therapies in the management of non-metastatic castration-resistant prostate cancer: a literature-based meta-analysis of randomized trials

Abstract

Background

Materials and methods

Results

Conclusions

Neu im Fachgebiet Onkologie

Stereotaktische Radiatio schlägt konventionelle Bestrahlung

Adjuvante Brustkrebstherapie: Doppelt hält besser

Manche Gestagene können das Risiko für Meningeome erhöhen

Einladung zum PSA-Screening senkt die Krebssterblichkeit

Update Onkologie

Live-Webinar: Aktuelle Leitlinien bei Herz-Kreislauf-Erkrankungen

Springer Medizin

Abstract

Background

Materials and methods

Results

Conclusions

Bitte loggen Sie sich ein, um Zugang zu diesem Inhalt zu erhalten

Weitere Artikel der Ausgabe 7/2020

Situation, challenges, and SEOM recommendations for the future of undergraduate education in Oncology in Spain

Dual-targeted therapeutic strategy combining CSC–DC-based vaccine and cisplatin overcomes chemo-resistance in experimental mice model

The prognostic role of FZD6 in esophageal squamous cell carcinoma patients

Effects of radiotherapy on plasma energy metabolites in patients with breast cancer who received neoadjuvant chemotherapy

Li–Fraumeni syndrome heterogeneity

HLA-G as a new tumor biomarker: detection of soluble isoforms of HLA-G in the serum and saliva of patients with colorectal cancer

Neu im Fachgebiet Onkologie

Stereotaktische Radiatio schlägt konventionelle Bestrahlung

Adjuvante Brustkrebstherapie: Doppelt hält besser

Manche Gestagene können das Risiko für Meningeome erhöhen

Einladung zum PSA-Screening senkt die Krebssterblichkeit

Update Onkologie