Chronological transition in outcome of second-line treatment in patients with metastatic urothelial cancer after pembrolizumab approval: a multicenter retrospective analysis

Int J Clin Oncol. 2022 Jan;27(1):165-174. doi: 10.1007/s10147-021-02046-z. Epub 2021 Oct 11.

Abstract

Background: After first-line chemotherapy failure, metastatic urothelial carcinoma (mUC) patients undergo pembrolizumab (PEM) or gemcitabine and docetaxel (GD) therapy. We retrospectively investigated outcomes of second-line GD or PEM for mUC patients.

Methods: A total of 198 mUC patients from Nagoya City University and affiliated hospitals who received second-line treatment were grouped according to immune check point inhibitor (ICI) availability: Groups A (pre-ICI: n = 104) and B (post-ICI: n = 94). We compared clinical outcomes using Kaplan-Meier curves. Univariate and multivariate Cox regression analyses assessed potential prognostic factors for overall survival (OS).

Results: Median OS was significantly longer for Group B [median 13.6 months, 95% confidence interval (CI): 7.6-17.6] than A (7.6 months, 5.3-8.8). By sub-group analysis, patients received no additional treatment (Naïve, n = 70), or PEM or GD (Salvage, n = 24) in Group B, with median OS of Naïve and A groups similar. Compared to the Salvage group, significant differences in OS were observed (median 7.6 months, 95% CI 5.3-8.8; Group A, 7.6 months, 4.7-13.8; Naïve, 25.7 months, 14.0-31.0; p < 0.01). For the Salvage group, OS for sequential treatment of GD-salvage PEM and PEM-salvage GD patients was similar (p = 0.10). Multivariate analysis showed a low neutrophil-to-lymphocyte ratio (NLR) and high geriatric nutritional risk index (GNRI) as significant prognostic factors affecting long OS [95% CI 1.12-3.45, hazard ratio (HR): 1.97; 95% CI 0.24-0.71, 0.41, respectively].

Conclusion: Second-line GD or PEM therapy for mUC patients showed equivalent survival benefits. GNRI and NLR are prognostic biomarkers for survival outcome.

Keywords: Gemcitabine and docetaxel; Geriatric nutritional index; Metastatic urothelial carcinoma; Pembrolizumab.

Publication types

  • Multicenter Study

MeSH terms

  • Aged
  • Antibodies, Monoclonal, Humanized / therapeutic use*
  • Carcinoma, Transitional Cell* / drug therapy
  • Deoxycytidine / analogs & derivatives
  • Deoxycytidine / therapeutic use
  • Docetaxel / therapeutic use
  • Gemcitabine
  • Humans
  • Retrospective Studies
  • Urinary Bladder Neoplasms* / drug therapy

Substances

  • Antibodies, Monoclonal, Humanized
  • Deoxycytidine
  • Docetaxel
  • pembrolizumab
  • Gemcitabine