TY - JOUR
TI - Fourth-line therapy in metastatic renal cell carcinoma (mRCC): Results from the international mRCC database consortium (IMDC)
AU - Stukalin, I.
AU - Connor Wells, J.
AU - Fraccon, A.
AU - Pasini, F.
AU - Porta, C.
AU - Lalani, A.-K.A.
AU - Srinivas, S.
AU - Alex Bowman, I.
AU - Brugarolas, J.
AU - Lee, J.-L.
AU - Donskov, F.
AU - Beuselinck, B.
AU - Bamias, A.
AU - Rini, B.I.
AU - Sim, H.-W.
AU - Agarwal, N.
AU - Rha, S.-Y.
AU - Kanesvaran, R.
AU - Choueiri, T.K.
AU - Heng, D.Y.C.
JO - Kidney Cancer
PY - 2018
VL - 2
TODO - 1
SP - 31-36
PB - IOS Press BV
SN - null
TODO - 10.3233/KCA-170020
TODO - axitinib;  pazopanib;  sorafenib;  sunitinib, adult;  aged;  Article;  cancer prognosis;  cancer survival;  clinical outcome;  cohort analysis;  data base;  female;  high risk patient;  human;  intermediate risk patient;  kidney metastasis;  low risk patient;  major clinical study;  male;  multicenter study (topic);  overall survival;  priority journal;  progression free survival;  retrospective study;  treatment response
TODO - 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. © 2018 - IOS Press and the authors. All rights reserved
ER -