Top

Published in:

Open Access 01-12-2021 | Prostate Cancer | Research

Corticosteroid switch from prednisone to dexamethasone in metastatic castration-resistant prostate cancer patients with biochemical progression on abiraterone acetate plus prednisone

Authors: Zhenyu Yang, Yuchao Ni, Diwei Zhao, Yijun Zhang, Jun Wang, Lijuan Jiang, Dong Chen, Zhiming Wu, Yanjun Wang, Liru He, Yanxia Shi, Fangjian Zhou, Hao Zeng, Yonghong Li

Published in: BMC Cancer | Issue 1/2021

Abstract

Background

To assess the efficacies and potential predictors of a corticosteroid switch in metastatic castration-resistant prostate cancer (mCRPC) patients with biochemical progression on abiraterone acetate plus prednisone (A + P).

Methods

Patients with mCRPC treated between April 2016 and August 2020, who experienced biochemical progression on A + P and then switched to A plus dexamethasone (D), were retrospectively identified. The primary endpoint was progression-free survival (PFS), and the secondary endpoints were PSA response, overall survival (OS), and safety.

Results

One hundred and thirty consecutive cases were enrolled. The median PFS and OS on A + D were 5.0 and 18.7 months, respectively. The best PSA decline of ≥50% (PSA50) and ≥ 30% (PSA30) were observed in 29.2 and 46.2% patients, respectively. Lower PSA at corticosteroid switch (≤ 20 ng/mL; median PFS, HR 0.63, p = 0.019; median OS, HR 0.38, p = 0.001) and longer mCRPC-free survival (≥ 18 months; median PFS, HR 0.61, p = 0.013; median OS, HR 0.51, p = 0.015) were identified as independent prognostic predictors associated with longer PFS and OS. A risk stratification tool was developed to select candidates for corticosteroid switch based on the independent prognostic predictors of PFS and OS.

Conclusions

A corticosteroid switch from prednisone to dexamethasone is effective for mCRPC which progressed on A + P treatment. Patients with lower PSA at corticosteroid switch and/or longer mCRPC-free survival may gain more benefits by the corticosteroid switch.

Sung H, Ferlay J, Siegel RL, Laversanne M, Soerjomataram I, Jemal A, et al. Global cancer statistics 2020: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin. 2021;71(3):209–49.

Beer TM, Armstrong AJ, Rathkopf DE, Loriot Y, Sternberg CN, Higano CS, et al. Enzalutamide in metastatic prostate cancer before chemotherapy. N Engl J Med. 2014;371(5):424–33. https://doi.org/10.1056/NEJMoa1405095.CrossRefPubMedPubMedCentral

Ryan CJ, Smith MR, Fizazi K, Saad F, Mulders PF, Sternberg CN, et al. 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, double-blind, placebo-controlled phase 3 study. Lancet Oncol. 2015;16(2):152–60. https://doi.org/10.1016/S1470-2045(14)71205-7.CrossRef

de Wit R, de Bono J, Sternberg CN, Fizazi K, Tombal B, Wulfing C, et al. Cabazitaxel versus Abiraterone or Enzalutamide in Metastatic Prostate Cancer. N Engl J Med. 2019;381(26):2506–18. https://doi.org/10.1056/NEJMoa1911206.CrossRefPubMed

Parker C, Nilsson S, Heinrich D, Helle SI, O'Sullivan JM, Fossa SD, et al. Alpha emitter radium-223 and survival in metastatic prostate cancer. N Engl J Med. 2013;369(3):213–23. https://doi.org/10.1056/NEJMoa1213755.CrossRefPubMed

Yin L, Hu Q. CYP17 inhibitors--abiraterone, C17,20-lyase inhibitors and multi-targeting agents. Nat Rev Urol. 2014;11(1):32–42. https://doi.org/10.1038/nrurol.2013.274.CrossRefPubMed

Attard G, Reid AH, Yap TA, Raynaud F, Dowsett M, Settatree S, et al. Phase I clinical trial of a selective inhibitor of CYP17, abiraterone acetate, confirms that castration-resistant prostate cancer commonly remains hormone driven. J Clin Oncol. 2008;26(28):4563–71. https://doi.org/10.1200/JCO.2007.15.9749.CrossRefPubMed

Fizazi K, Scher HI, Molina A, Logothetis CJ, Chi KN, Jones RJ, et al. Abiraterone acetate for treatment of metastatic castration-resistant prostate cancer: final overall survival analysis of the COU-AA-301 randomised, double-blind, placebo-controlled phase 3 study. Lancet Oncol. 2012;13(10):983–92. https://doi.org/10.1016/S1470-2045(12)70379-0.CrossRefPubMed

Reid AH, Attard G, Danila DC, Oommen NB, Olmos D, Fong PC, et al. Significant and sustained antitumor activity in post-docetaxel, castration-resistant prostate cancer with the CYP17 inhibitor abiraterone acetate. J Clin Oncol. 2010;28(9):1489–95. https://doi.org/10.1200/JCO.2009.24.6819.CrossRefPubMedPubMedCentral

10.

Danila DC, Morris MJ, de Bono JS, Ryan CJ, Denmeade SR, Smith MR, et al. Phase II multicenter study of abiraterone acetate plus prednisone therapy in patients with docetaxel-treated castration-resistant prostate cancer. J Clin Oncol. 2010;28(9):1496–501. https://doi.org/10.1200/JCO.2009.25.9259.CrossRefPubMedPubMedCentral

11.

Attard G, Merseburger AS, Arlt W, Sternberg CN, Feyerabend S, Berruti A, et al. Assessment of the safety of glucocorticoid regimens in combination with Abiraterone acetate: a randomized, open-label phase 2 study. JAMA Oncol. 2019;5(8):1159–67. https://doi.org/10.1001/jamaoncol.2019.1011.CrossRefPubMedPubMedCentral

12.

Fenioux C, Louvet C, Charton E, Rozet F, Ropert S, Prapotnich D, et al. Switch from abiraterone plus prednisone to abiraterone plus dexamethasone at asymptomatic PSA progression in patients with metastatic castration-resistant prostate cancer. BJU Int. 2019;123(2):300–6. https://doi.org/10.1111/bju.14511.CrossRefPubMed

13.

Lorente D, Omlin A, Ferraldeschi R, Pezaro C, Perez R, Mateo J, et al. Tumour responses following a steroid switch from prednisone to dexamethasone in castration-resistant prostate cancer patients progressing on abiraterone. Br J Cancer. 2014;111(12):2248–53. https://doi.org/10.1038/bjc.2014.531.CrossRefPubMedPubMedCentral

14.

Romero-Laorden N, Lozano R, Jayaram A, Lopez-Campos F, Saez MI, Montesa A, et al. Phase II pilot study of the prednisone to dexamethasone switch in metastatic castration-resistant prostate cancer (mCRPC) patients with limited progression on abiraterone plus prednisone (SWITCH study). Br J Cancer. 2018;119(9):1052–9. https://doi.org/10.1038/s41416-018-0123-9.CrossRefPubMedPubMedCentral

15.

Roviello G, Petrioli R, Bonetta A, Conca R, Rodriquenz MG, Aieta M. Corticosteroid switch in heavily pre-treated castration-resistant prostate cancer patients progressed on abiraterone acetate plus prednisone. Investig New Drugs. 2018;36(6):1110–5. https://doi.org/10.1007/s10637-018-0685-7.CrossRef

16.

Rivero Belenchón I, Muñoz Calahorro C, Osmán García I, Beardo Villar P, Congregado Ruíz CB, Ruíz SJ, et al. 577 - switching from prednisone to dexamethasone in metastatic castration resistant prostate cancer treated with abiraterone acetate in a multicenter study. Eur Urol Open Sci. 2020;19:e897–8. https://doi.org/10.1016/S2666-1683(20)33180-3.CrossRef

17.

Zanardi E, Soldato D, Latocca MM, Cattrini C, Boccardo F. To switch or not to switch? A real-life experience using dexamethasone in combination with abiraterone. Ther Adv Urol. 2019;11:1756287219854908.CrossRef

18.

Fang WY, Wang PF, Fan YC, Shih HJ. Clinical experience of steroid switch from prednisone to dexamethasone in patients with metastatic castration-resistant prostate Cancer treated with Abiraterone acetate. Urol Int. 2021;105(5–6):380–5.

19.

Scher HI, Morris MJ, Stadler WM, Higano C, Basch E, Fizazi K, et al. Trial design and objectives for castration-resistant prostate Cancer: updated recommendations from the prostate Cancer clinical trials working group 3. J Clin Oncol. 2016;34(12):1402–18. https://doi.org/10.1200/JCO.2015.64.2702.CrossRefPubMedPubMedCentral

20.

Roviello G, Sobhani N, Corona SP, D'Angelo A. Corticosteroid switch after progression on abiraterone acetate plus prednisone. Int J Clin Oncol. 2020;25(2):240–6. https://doi.org/10.1007/s10147-019-01577-w.CrossRefPubMed

21.

Arora VK, Schenkein E, Murali R, Subudhi SK, Wongvipat J, Balbas MD, et al. Glucocorticoid receptor confers resistance to antiandrogens by bypassing androgen receptor blockade. Cell. 2013;155(6):1309–22. https://doi.org/10.1016/j.cell.2013.11.012.CrossRefPubMedPubMedCentral

22.

Richards J, Lim AC, Hay CW, Taylor AE, Wingate A, Nowakowska K, et al. Interactions of abiraterone, eplerenone, and prednisolone with wild-type and mutant androgen receptor: a rationale for increasing abiraterone exposure or combining with MDV3100. Cancer Res. 2012;72(9):2176–82. https://doi.org/10.1158/0008-5472.CAN-11-3980.CrossRefPubMedPubMedCentral

23.

Diederich S, Scholz T, Eigendorff E, Bumke-Vogt C, Quinkler M, Exner P, et al. Pharmacodynamics and pharmacokinetics of synthetic mineralocorticoids and glucocorticoids: receptor transactivation and prereceptor metabolism by 11beta-hydroxysteroid-dehydrogenases. Horm Metab Res. 2004;36(6):423–9. https://doi.org/10.1055/s-2004-814578.CrossRefPubMed

24.

Lan NC, Graham B, Bartter FC, Baxter JD. Binding of steroids to mineralocorticoid receptors: implications for in vivo occupancy by glucocorticoids. J Clin Endocrinol Metab. 1982;54(2):332–42. https://doi.org/10.1210/jcem-54-2-332.CrossRefPubMed

25.

Yano A, Fujii Y, Iwai A, Kawakami S, Kageyama Y, Kihara K. Glucocorticoids suppress tumor lymphangiogenesis of prostate cancer cells. Clin Cancer Res. 2006;12(20 Pt 1):6012–7. https://doi.org/10.1158/1078-0432.CCR-06-0749.CrossRefPubMed

26.

Attard G, Reid AH, A'Hern R, Parker C, Oommen NB, Folkerd E, et al. Selective inhibition of CYP17 with abiraterone acetate is highly active in the treatment of castration-resistant prostate cancer. J Clin Oncol. 2009;27(23):3742–8. https://doi.org/10.1200/JCO.2008.20.0642.CrossRefPubMed

27.

Venkitaraman R, Lorente D, Murthy V, Thomas K, Parker L, Ahiabor R, et al. A randomised phase 2 trial of dexamethasone versus prednisolone in castration-resistant prostate cancer. Eur Urol. 2015;67(4):673–9. https://doi.org/10.1016/j.eururo.2014.10.004.CrossRefPubMed

Title: Corticosteroid switch from prednisone to dexamethasone in metastatic castration-resistant prostate cancer patients with biochemical progression on abiraterone acetate plus prednisone
Authors: Zhenyu Yang
Yuchao Ni
Diwei Zhao
Yijun Zhang
Jun Wang
Lijuan Jiang
Dong Chen
Zhiming Wu
Yanjun Wang
Liru He
Yanxia Shi
Fangjian Zhou
Hao Zeng
Yonghong Li
Publication date: 01-12-2021
Publisher: BioMed Central
Keywords: Prostate Cancer
Prostate Cancer
Dexamethasone
Published in: BMC Cancer / Issue 1/2021
Electronic ISSN: 1471-2407
DOI: https://doi.org/10.1186/s12885-021-08670-2

Webinar | 19-02-2024 | 17:30 (CET)

Keynote webinar | Spotlight on antibody–drug conjugates in cancer

Watch now

Antibody–drug conjugates (ADCs) are novel agents that have shown promise across multiple tumor types. Explore the current landscape of ADCs in breast and lung cancer with our experts, and gain insights into the mechanism of action, key clinical trials data, existing challenges, and future directions.

Dr. Véronique Diéras

Prof. Fabrice Barlesi

Developed by: Springer Medicine

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Abstract

Background

Methods

Results

Conclusions

Please log in to get access to this content

Other articles of this Issue 1/2021

The development and validation of the psychological capital questionnaire for patients with Cancer the psychological capital questionnaire

Stemness-related LncRNA pair signature for predicting therapy response in gastric cancer

Efficacy and safety of rucaparib in previously treated, locally advanced or metastatic urothelial carcinoma from a phase 2, open-label trial (ATLAS)

New insights of the correlation between AXIN2 polymorphism and cancer risk and susceptibility: evidence from 72 studies

Identification of novel prognostic biomarkers by integrating multi-omics data in gastric cancer

Ado-trastuzumab for the treatment of metastatic HER2-positive breast cancer in patients previously treated with Pertuzumab

Keynote webinar | Spotlight on antibody–drug conjugates in cancer