TY - JOUR
T1 - Everolimus Versus Sunitinib Prospective Evaluation in Metastatic Non-Clear Cell Renal Cell Carcinoma (ESPN)
T2 - A Randomized Multicenter Phase 2 Trial
AU - Tannir, Nizar M.
AU - Jonasch, Eric
AU - Albiges, Laurence
AU - Altinmakas, Emre
AU - Ng, Chaan S.
AU - Matin, Surena F.
AU - Wang, Xuemei
AU - Qiao, Wei
AU - Dubauskas Lim, Zita
AU - Tamboli, Pheroze
AU - Rao, Priya
AU - Sircar, Kanishka
AU - Karam, Jose A.
AU - McDermott, David F.
AU - Wood, Christopher G.
AU - Choueiri, Toni K.
N1 - Funding Information:
Funding/Support and role of the sponsor: The trial was funded by Novartis, and supported by NIH/NCI award P30CA016672. The trial was also funded in part by the Dana-Farber/Harvard Cancer Center Kidney Cancer Specialized Program of Research Excellence, the Trust Family, Michael Brigham, and Loker Pinard Funds for Kidney Cancer Research for Toni K. Choueiri. Novartis had no role in the study design, data collection, analysis, interpretation, or writing of the report. The corresponding author had full access to all the data in the study and had final responsibility for the decision to submit for publication.
Publisher Copyright:
© 2015 European Association of Urology. Published by Elsevier B.V. All rights reserved.
PY - 2016/5/1
Y1 - 2016/5/1
N2 - Background Sunitinib and everolimus are standard first-line and second-line therapies, respectively, in clear cell renal cell carcinoma (ccRCC). Objective To conduct a randomized phase 2 trial comparing sunitinib and everolimus in non-clear cell RCC (non-ccRCC). Design, setting, and participants Patients with metastatic, non-ccRCC, or ccRCC with >20% sarcomatoid features (ccSRCC) were randomized to receive sunitinib or everolimus with crossover at disease progression. Outcome measurement and statistical analysis Primary end point was progression-free survival (PFS) in first-line therapy; 108 patients were needed to show improvement in median PFS (mPFS) from 12 wk with sunitinib to 20 wk with everolimus. Results and limitations Interim analysis of 68 patients (papillary [27], chromophobe [12], unclassified [10], translocation [7], ccSRCC [12]) prompted early trial closure. The mPFS in first-line therapy was 6.1 mo with sunitinib and 4.1 mo with everolimus (p = 0.6); median overall survival (mOS) was not reached with sunitinib and was 10.5 mo with everolimus, respectively (p = 0.014). At final analysis, mOS was 16.2 and 14.9 mo with sunitinib and everolimus, respectively (p = 0.18). There were four partial responses (PRs) in first-line therapy (sunitinib: 3 of 33 [9%]; everolimus, 1 of 35 [2.8%]) and four PRs in second-line therapy (sunitinib: 2 of 21 [9.5%]; everolimus, 2 of 23 [8.6%]), with mPFS of 1.8 mo and 2.8 mo, respectively. In patients without sarcomatoid features in their tumors (n = 49), mOS was 31.6 mo with sunitinib and 10.5 mo with everolimus (p = 0.075). Genomic profiling of a chromophobe RCC from a patient with a PR to first-line everolimus revealed a somatic TSC2 mutation. Conclusions In this trial, everolimus was not superior to sunitinib. Both agents demonstrated modest efficacy, underscoring the need for better therapies in non-ccRCC. Patient summary This randomized phase 2 trial provides the first head-to-head comparison of everolimus and sunitinib in patients with metastatic non-clear cell renal cell carcinoma (non-ccRCC). The observed very modest efficacy underscores the need to develop more effective therapies for non-ccRCC.
AB - Background Sunitinib and everolimus are standard first-line and second-line therapies, respectively, in clear cell renal cell carcinoma (ccRCC). Objective To conduct a randomized phase 2 trial comparing sunitinib and everolimus in non-clear cell RCC (non-ccRCC). Design, setting, and participants Patients with metastatic, non-ccRCC, or ccRCC with >20% sarcomatoid features (ccSRCC) were randomized to receive sunitinib or everolimus with crossover at disease progression. Outcome measurement and statistical analysis Primary end point was progression-free survival (PFS) in first-line therapy; 108 patients were needed to show improvement in median PFS (mPFS) from 12 wk with sunitinib to 20 wk with everolimus. Results and limitations Interim analysis of 68 patients (papillary [27], chromophobe [12], unclassified [10], translocation [7], ccSRCC [12]) prompted early trial closure. The mPFS in first-line therapy was 6.1 mo with sunitinib and 4.1 mo with everolimus (p = 0.6); median overall survival (mOS) was not reached with sunitinib and was 10.5 mo with everolimus, respectively (p = 0.014). At final analysis, mOS was 16.2 and 14.9 mo with sunitinib and everolimus, respectively (p = 0.18). There were four partial responses (PRs) in first-line therapy (sunitinib: 3 of 33 [9%]; everolimus, 1 of 35 [2.8%]) and four PRs in second-line therapy (sunitinib: 2 of 21 [9.5%]; everolimus, 2 of 23 [8.6%]), with mPFS of 1.8 mo and 2.8 mo, respectively. In patients without sarcomatoid features in their tumors (n = 49), mOS was 31.6 mo with sunitinib and 10.5 mo with everolimus (p = 0.075). Genomic profiling of a chromophobe RCC from a patient with a PR to first-line everolimus revealed a somatic TSC2 mutation. Conclusions In this trial, everolimus was not superior to sunitinib. Both agents demonstrated modest efficacy, underscoring the need for better therapies in non-ccRCC. Patient summary This randomized phase 2 trial provides the first head-to-head comparison of everolimus and sunitinib in patients with metastatic non-clear cell renal cell carcinoma (non-ccRCC). The observed very modest efficacy underscores the need to develop more effective therapies for non-ccRCC.
KW - Everolimus
KW - Non-clear cell renal cell carcinoma
KW - Renal cell carcinoma
KW - Sunitinib
UR - http://www.scopus.com/inward/record.url?scp=84949494071&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84949494071&partnerID=8YFLogxK
U2 - 10.1016/j.eururo.2015.10.049
DO - 10.1016/j.eururo.2015.10.049
M3 - Article
C2 - 26626617
AN - SCOPUS:84949494071
SN - 0302-2838
VL - 69
SP - 866
EP - 874
JO - European urology
JF - European urology
IS - 5
ER -