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Impact of new systemic therapies on overall survival of patients with metastatic castration-resistant prostate cancer in a hospital-based registry

Prostate Cancer and Prostatic Diseases volume 22, pages 420–427 (2019)Cite this article

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Abstract

Background

In 2004, docetaxel was shown to prolong the overall survival (OS) of patients with metastatic castration-resistance prostate cancer (mCRPC). Since 2010, five new systemic therapies have been shown to prolong OS in men with mCRPC. We sought to evaluate the aggregate impact of these newer therapies on the OS of patients with mCRPC.

Methods

Two cohorts of patients diagnosed with mCRPC between 2004 and 2007, treated with drugs used in the limited treatment era only (A), and between 2010 and 2013, treated also with newer therapies (B), were identified from the Dana-Farber Cancer Institute database. The analysis endpoint was OS within 5 years after mCRPC diagnosis. Kaplan–Meier method assessed time-to-event distributions with median (95% confidence interval (CI)). A piece-wise regression model assessed the association between endpoint and treatment cohorts with estimate of hazard ratio (HR) with 95% CI within two time segments in univariate and multivariable analyses adjusting for relevant covariates.

Results

Compared to cohort A (n = 318), cohort B (n = 272) patients in newer therapy era demonstrated an OS advantage (2.8 vs. 2.2 years) with a 41% decreased risk of death (HR = 0.59; 95% CI, 0.47–0.74; P < 0.0001), and a 3-year OS rate of 46% vs. 33%. This benefit was accentuated (median OS 2.7 vs. 2.1 years; HR = 0.46; 95% CI, 0.32–0.67; P < 0.0001) in patients who initially presented with de-novo metastatic disease (de-novo). On multivariable analysis, longer OS was associated with cohort B vs. A and performance status 0 vs. 1.

Conclusions

Using a single-institution registry, mCRPC patients treated since 2010 had a significant survival improvement vs. those treated before 2010. Although the median survival was only modestly improved and less than predicted when simply adding each newer drug survival advantage, the cumulative benefit from the new therapies was more pronounced in longer-term survivors and de-novo patients.

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Acknowledgements

Author contributions

Conception and design: EF, KPG, and CJS; collection and assembly of data: EF, GKS, CPE, AAH, and CEP; data analysis and interpretation: EF, KPG, PWK, M-ET, and CJS; manuscript writing: all authors; final approval of the manuscript: all authors; accountable for all aspects of the work: all authors.

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Authors and Affiliations

  1. Lank Center for Genitourinary Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA, USA

    Edoardo Francini, Kathryn P. Gray, Grace K. Shaw, Carolyn P. Evan, Anis A. Hamid, Caitlin E. Perry, Mary-Ellen Taplin & Christopher J. Sweeney

  2. Sapienza Università di Roma, Rome, Italy

    Edoardo Francini

  3. Memorial Sloan Kettering Cancer Center, New York, NY, USA

    Philip W. Kantoff

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  1. Edoardo Francini
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Correspondence to Christopher J. Sweeney.

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Conflict of interest

EF has been sponsored for travel, accommodations, and expenses by Janssen-Cilag. AAH has participated in advisory boards for Roche and received compensation. PWK has consulted or participated in advisory boards for Astellas, Bayer, Genentech, Janssen-Cilag, Merck, Sanofi, Dendreon, Medivation/Astellas, and Pfizer and received compensation; he also received grants or funding from Bayer, Dendreon, Genentech/Roche, and Medivation/Astellas, and has been sponsored for travel, accommodations, expenses by Sanofi. M-ET has consulted or participated in advisory boards for Janssen-Cilag and Medivation and received compensation: she also received grants or funding by Janssen-Cilag and Medivation, Travel, and has been sponsored for travel, accommodations, expenses by Sanofi. CJS has consulted or participated in advisory boards for Astellas, Bayer, Genentech, Janssen-Cilag, Pfizer, and Sanofi, and received compensation: he also received grants or funding by Astellas, Janssen-Cilag, Sotio, and Sanofi. KPG, GKS, CPE, and CEP declare that they have no conflict of interest.

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Francini, E., Gray, K.P., Shaw, G.K. et al. Impact of new systemic therapies on overall survival of patients with metastatic castration-resistant prostate cancer in a hospital-based registry. Prostate Cancer Prostatic Dis 22, 420–427 (2019). https://doi.org/10.1038/s41391-018-0121-2

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