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Angiogenesis

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A new prognostic model for survival in second line for metastatic renal cell carcinoma: development and external validation

  • Lisa DerosaEmail author
  • Mohamed Amine Bayar
  • Laurence Albiges
  • Gwénaël Le Teuff
  • Bernard Escudier
Original Paper

Abstract

Background

In patients with metastatic renal cell carcinoma (mRCC), the oncologic benefit of second-line treatment for high volume tumors or presence of more than five risk factors remain to be defined. Our aim was to develop and externally validate a new model most likely to correctly predict overall survival (OS) categories in second line.

Method

mRCC patients treated within clinical trials at Gustave Roussy Cancer Campus (GRCC) formed the discovery set. Patients from two phase III trials from Pfizer database (PFIZERDB), AXIS (NCT00678392), and INTORSECT (NCT00474786), formed the external validation set. New prognostic factors were analyzed using a multivariable Cox model with a backward selection procedure. Performance of the GRCC model and the prognostic classification scheme derived from it, measuring by R2, c-index, and calibration, was evaluated on the validation set and compared to MSKCC and IMDC models.

Results

Two hundred and twenty-one patients were included in the GRCC cohort and 855 patients in the PFIZERDB. Median OS was similar in the discovery and validation cohorts (16.8 [95% CI 12.9–21.7] and 15.3 [13.6–17.2] months, respectively). Backward selection procedure identified time from first to second-line treatment and tumor burden as new independent prognostic factors significantly associated to OS after adjusting for IMDC prognostic factors (HR 1.68 [1.23–2.31] and 1.43 [1.03–1.99], respectively). Dividing patients into four risk groups, based on the number of factors selected in GRCC model, median OS from the start of second line in the validation cohort was not reached (NE) [95% CI 24.9–NE] in the favorable risk group (n = 20), 21.8 months [18.6–28.2] in the intermediate-risk group (n = 367), 12.7 months [11.0–15.8] in the low poor-risk group (n = 347), and 5.5 months [4.7–6.4] in the high poor-risk group (n = 121). Finally, this model and its prognostic classification scheme provided the better fit, with higher R2 and higher c-index compared to other possible classification schemes.

Conclusion

A new prognostic model was developed and validated to estimate overall survival of patients with previously treated mRCC. This model is an easy-to-use tool that allows accurate estimation of patient survival to inform decision making and follow-up after first line for mRCC.

Keywords

MSKCC IMDC Metastatic renal cell carcinoma Second line Prognostic model Tumor burden Time from first to second line 

Notes

Acknowledgements

LD was supported by Gustave Roussy Fondation Philanthropia, by Gustave Roussy DUERTECC program, and by ESMO translational research fellowship. We thank Pfizer laboratory for provided data used for the external validation.

Author contributions

Conception and design: LD, MAB, GLT, BE. Financial support: None. Provision of study materials or patients: LD, BE, LA. Collection and assembly of data: LD. Data analysis and interpretation: MAB, GLT. Manuscript writing: LD, MAB, GLT, BE. Final approval of manuscript: All authors.

Compliance with ethical standards

Conflict of interest

The author(s) indicated no potential conflicts of interest. This work won the 2018 ESMO Merit Award.

Supplementary material

10456_2019_9664_MOESM1_ESM.docx (498 kb)
Supplementary material 1 (DOCX 498 KB)

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Copyright information

© Springer Nature B.V. 2019

Authors and Affiliations

  1. 1.Departments of Medical OncologyGustave RoussyVillejuifFrance
  2. 2.Université Paris-Sud, Université Paris-SaclayVillejuifFrance
  3. 3.Institut National de la Santé Et de la Recherche Médicale (INSERM) U1015VillejuifFrance
  4. 4.Equipe Labellisée-Ligue Nationale contre le CancerVillejuifFrance
  5. 5.Department of Biostatistics and Epidemiology and Ligue National Contre le Cancer meta-analysis platformGustave RoussyVillejuifFrance
  6. 6.U1018 INSERM, CESPUniversité Paris-Sud, Université Paris-SaclayVillejuifFrance

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