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Longitudinal model–based meta-analysis for survival probabilities in patients with castration-resistant prostate cancer

  • Wenjun Chen
  • Liang LiEmail author
  • Shuangmin Ji
  • Xuyang Song
  • Wei Lu
  • Tianyan ZhouEmail author
Pharmacodynamics

Abstract

Purpose

The aims of this longitudinal model-based meta-analysis (MBMA) were to indirectly compare the time courses of survival probabilities and to identify corresponding potential significant covariates across approved drugs in patients with castration-resistant prostate cancer (CRPC).

Methods

A systematic literature review for monotherapy studies in patients with CRPC was conducted up to August 8, 2018. The time courses of progression-free survival (PFS) and overall survival (OS) were fitted with parametric survival models. Covariate analyses were performed to determine the impact of treatment drugs, dosing regimens, and patient characteristics on the survival probabilities. Simulations were carried out to quantify the magnitude of covariate effects.

Results

A total of 146 studies including clinical trials and real-world data on longitudinal survival probabilities in 20,712 patients with CRPC were included in our meta-database. The time courses of PFS and OS probabilities were best described by the log-logistic model. There was no significant difference in median OS and PFS between docetaxel, cabazitaxel, abiraterone acetate, and enzalutamide. There was no significant dose-response relationship in PFS or OS for docetaxel at 50 to 120 mg/m2 every 3 weeks (Q3W) and cabazitaxel at 20 to 25 mg/m2 Q3W. Model-based simulations indicated that PFS probability was associated with chemotherapy, Gleason score, and baseline prostate-specific antigen (BLPSA), while OS probability was associated with chemotherapy, Gleason score, visceral metastasis, Eastern Cooperative Oncology Group performance status, and BLPSA.

Conclusion

Our modeling and simulation framework can be applied to support indirect comparison, dose selection, and go/no-go decision-making for new agents targeting CRPC.

Keywords

Model-based meta-analysis Castration-resistant prostate cancer Progression-free survival Overall survival Longitudinal data 

Notes

Authors’ contributions

Li L, Zhou TY, Lu W, Chen WJ, Ji SM, and Song XY designed the research; Chen WJ, Li L, and Ji SM performed the research; Chen WJ, Li L, and Song XY analyzed the data; Chen WJ, Li L, and Zhou TY wrote the article.

Funding information

This work was supported by the National Natural Science Foundation of China [Grant No. 81302831].

Compliance with ethical standards

Conflict of interest

The authors declare that they have no conflict of interest.

The views expressed in this paper are those of the authors and do not necessarily represent those of the China National Medical Products Administration.

Supplementary material

228_2020_2829_MOESM1_ESM.docx (22.4 mb)
ESM 1 (DOCX 22908 kb)

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Copyright information

© Springer-Verlag GmbH Germany, part of Springer Nature 2020

Authors and Affiliations

  1. 1.Beijing Key Laboratory of Molecular Pharmaceutics and New Drug Delivery System, Department of Pharmaceutics, School of Pharmaceutical SciencesPeking UniversityBeijingChina
  2. 2.Center for Drug EvaluationNational Medical Products AdministrationBeijingChina
  3. 3.Department of Pharmaceutics, College of PharmacyUniversity of FloridaGainesvilleUSA

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