Fourth-line therapy in metastatic renal cell carcinoma (mRCC): Results from the international mRCC database consortium (IMDC)

Igor Stukalin, J. Connor Wells, Anna Fraccon, Felice Pasini, Camillo Porta, Aly Khan A. Lalani, Sandy Srinivas, I. Alex Bowman, James Brugarolas, Jae Lyun Lee, Frede Donskov, Benoit Beuselinck, Aristotelis Bamias, Brian I. Rini, Hao Wen Sim, Neeraj Agarwal, Sun Young Rha, Ravindran Kanesvaran, Toni K. Choueiri, Daniel Y.C. Heng

Research output: Contribution to journalArticlepeer-review

Abstract

Background: Fourth-line therapy (4LT) in the treatment of metastatic renal cell carcinoma (mRCC) varies significantly due to the lack of data and recommendations to guide treatment decisions. Objective: To evaluate the use and efficacy of 4LT in mRCC patients. Methods: The International mRCC Database Consortium (IMDC) dataset was used to identify patients with mRCC treated with 4LT. This is a multicenter, retrospective cohort study. Overall survival (OS) and progression-free survival (PFS) were calculated using Kaplan-Meier curves. Patients were evaluated for overall response. The six prognostic variables included in the IMDC prognostic model were used to stratify patients into favorable-, intermediate- and poor-risk groups. Exploratory analyses were performed examining the elderly (>70 years old) and non-clear cell RCC subgroups. Proportional hazards regression modelling was performed adjusting these covariates by IMDC criteria measured at initiation of 4th line therapy. Results: 7498 patients were treated with first line targeted therapy and out of these 594 (7.9%) received 4LT. Everolimus was the most frequently used 4LT (16.8%). Sorafenib, axitinib, pazopanib, sunitinib and clinical trial drugs were also used in >10% of patients. The OS of patients on any 4LT was 12.8 months, with a PFS of 4.4 months. The overall response rate (ORR) was 13.7%. Favorable-risk patients using IMDC criteria (5%) displayed an OS of 23.1 months, intermediate-risk patients (66%) had an OS of 13.8 months and poor-risk patients (29%) had an OS of 7.8 (p < 0.0001) months. Age >70 years and non-clear cell histology did not impact OS. Our study is limited by its retrospective design. Conclusions: 4LT use appears to have activity in mRCC patients. The IMDC continues to be of prognostic value in the fourth-line setting for OS. This study helps to set a benchmark for response rate and survival for which clinical trials can plan sample size calculations and aim to improve upon.

Original languageEnglish (US)
Pages (from-to)31-36
Number of pages6
JournalKidney Cancer
Volume2
Issue number1
DOIs
StatePublished - 2018

Keywords

  • Checkpoint inhibitors
  • Fourth line therapy
  • Metastatic renal cell carcinoma
  • Targeted therapy

ASJC Scopus subject areas

  • Nephrology
  • Oncology

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