Five-Factor Prognostic Model for Survival of Post-Platinum Patients with Metastatic Urothelial Carcinoma Receiving PD-L1 Inhibitors

Guru Sonpavde, Juliane Manitz, Chen Gao, Darren Tayama, Constanze Kaiser, Daniel Hennessy, Doris Makari, Ashok Gupta, Shaad Essa Abdullah, Guenter Niegisch, Jonathan E. Rosenberg, Dean F. Bajorin, Petros Grivas, Andrea B. Apolo, Robert Dreicer, Noah M. Hahn, Matthew D. Galsky, Andrea Necchi, Sandy Srinivas, Thomas PowlesToni K. Choueiri, Gregory R. Pond

Research output: Contribution to journalArticlepeer-review

5 Scopus citations

Abstract

Purpose:A prognostic model for overall survival of post-platinum patients with metastatic urothelial carcinoma receiving PD-1/PD-L1 inhibitors is necessary as existing models were constructed in the chemotherapy setting.Materials and Methods:Patient level data were used from phase I/II trials evaluating PD-L1 inhibitors following platinum based chemotherapy for metastatic urothelial carcinoma. The derivation data set consisted of 2 phase I/II trials evaluating atezolizumab (405). Two phase I/II trials that evaluated avelumab (242) and durvalumab (198) comprised the validation data sets. Cox regression analyses evaluated the association of candidate prognostic factors with overall survival. Stepwise selection was used to select an optimal model using the derivation data set. Discrimination and calibration were assessed in the avelumab and durvalumab data sets.Results:The 5 prognostic factors identified in the optimal model using the atezolizumab derivation data set were ECOG-PS (1 vs 0, HR 1.80, 95% CI 1.36-2.36), liver metastasis (HR 1.55, 95% CI 1.20-2.00), platelet count (HR 2.22; 95% CI 1.54-3.18), neutrophil-to-lymphocyte ratio (HR 1.94, 95% CI 1.57-2.40) and lactate dehydrogenase (HR 1.60, 95% CI 1.28-1.99). There was robust discrimination of survival between low, intermediate and high risk groups. The c-statistic was 0.692 in the derivation and 0.671 and 0.773 in the avelumab and durvalumab validation data sets, respectively. A web based interactive tool was developed to calculate the expected survival probabilities based on risk factors.Conclusions:A validated 5-factor model has satisfactory prognostic performance for survival across 3 PD-L1 inhibitors to treat metastatic urothelial carcinoma after platinum therapy and may assist in stratification, interpreting and designing trials incorporating PD-1/PD-L1 inhibitors in the post-platinum setting.

Original languageEnglish (US)
Pages (from-to)1173-1179
Number of pages7
JournalJournal of Urology
Volume204
Issue number6
DOIs
StatePublished - Dec 1 2020

Keywords

  • carcinoma
  • drug therapy
  • neoplasm metastasis
  • platinum
  • prognosis
  • transitional cell

ASJC Scopus subject areas

  • Urology

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