Efficacy of Second-line Targeted Therapy for Renal Cell Carcinoma According to Change from Baseline in International Metastatic Renal Cell Carcinoma Database Consortium Prognostic Category

Eur Urol. 2017 Jun;71(6):970-978. doi: 10.1016/j.eururo.2016.09.047. Epub 2016 Oct 19.

Abstract

Background: We hypothesized that changes in International Metastatic Renal Cell Carcinoma Database Consortium (IMDC) prognostic category at start of second-line therapy (2L) for metastatic renal cell carcinoma (mRCC) might predict response.

Objective: To assess outcomes of 2L according to type of therapy and change in IMDC prognostic category.

Design, setting, and participants: We performed a retrospective review of the IMDC database for mRCC patients who received first-line (1L) VEGF inhibitors (VEGFi) and then 2L with VEGFi or mTOR inhibitors (mTORi). IMDC prognostic categories were defined before each line of therapy (favorable, F; intermediate, I; poor, P). Data were analyzed for 1516 patients, of whom 89% had clear cell histology.

Intervention: All included patients received targeted therapy for mRCC.

Outcome measurements and statistical analysis: Overall survival (OS), time to treatment failure, and response to 2L were analyzed using Cox or logistic regression.

Results and limitations: At start of 2L, 60% of patients remained in the same prognostic category; 9.0% improved (3% I → F; 6% P → I); 31% deteriorated (15% F → I or P; 16% I → P). Patients with the same or better IMDC prognostic category had a longer time to treatment failure if they remained on VEGFi compared to those who switched to mTORi (adjusted hazard ratio [AHR] ranging from 0.33 to 0.78, adjusted p<0.05). Patients who deteriorated from F to I appeared more likely to benefit from switching to mTORi (median OS 16.5 mo, 95% confidence interval [CI] 12.0-19.0 for VEGFi; 20.2 mo, 95% CI 14.3-26.1 for mTORi; AHR 1.53, 95% CI 1.04-2.24; adjusted p=0.03).

Conclusions: Changes in IMDC prognostic category predict the subsequent clinical course for patients with mRCC and provide a rational basis for selection of subsequent therapy.

Patient summary: The pattern of treatment failure might help to predict what the next treatment should be for patients with metastatic renal cell carcinoma.

Keywords: Carcinoma; Database; Follow-up studies; Logistic models; Renal cell.

Publication types

  • Comparative Study
  • Multicenter Study

MeSH terms

  • Angiogenesis Inhibitors / adverse effects
  • Angiogenesis Inhibitors / therapeutic use*
  • Carcinoma, Renal Cell / drug therapy*
  • Carcinoma, Renal Cell / enzymology
  • Carcinoma, Renal Cell / secondary
  • Databases, Factual
  • Disease Progression
  • Disease-Free Survival
  • Drug Substitution
  • Female
  • Humans
  • Kaplan-Meier Estimate
  • Kidney Neoplasms / drug therapy*
  • Kidney Neoplasms / enzymology
  • Kidney Neoplasms / pathology
  • Logistic Models
  • Male
  • Middle Aged
  • Molecular Targeted Therapy*
  • Multivariate Analysis
  • Odds Ratio
  • Proportional Hazards Models
  • Protein Kinase Inhibitors / adverse effects
  • Protein Kinase Inhibitors / therapeutic use*
  • Receptors, Vascular Endothelial Growth Factor / antagonists & inhibitors
  • Receptors, Vascular Endothelial Growth Factor / metabolism
  • Retrospective Studies
  • Signal Transduction / drug effects
  • TOR Serine-Threonine Kinases / antagonists & inhibitors
  • TOR Serine-Threonine Kinases / metabolism
  • Time Factors
  • Treatment Outcome
  • Vascular Endothelial Growth Factor A / antagonists & inhibitors
  • Vascular Endothelial Growth Factor A / metabolism

Substances

  • Angiogenesis Inhibitors
  • Protein Kinase Inhibitors
  • VEGFA protein, human
  • Vascular Endothelial Growth Factor A
  • MTOR protein, human
  • Receptors, Vascular Endothelial Growth Factor
  • TOR Serine-Threonine Kinases