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Clinical Trial
. 2016 May;69(5):866-74.
doi: 10.1016/j.eururo.2015.10.049. Epub 2015 Nov 26.

Everolimus Versus Sunitinib Prospective Evaluation in Metastatic Non-Clear Cell Renal Cell Carcinoma (ESPN): A Randomized Multicenter Phase 2 Trial

Nizar M Tannir  1 , Eric Jonasch  2 , Laurence Albiges  3 , Emre Altinmakas  4 , Chaan S Ng  4 , Surena F Matin  5 , Xuemei Wang  6 , Wei Qiao  6 , Zita Dubauskas Lim  2 , Pheroze Tamboli  7 , Priya Rao  7 , Kanishka Sircar  7 , Jose A Karam  5 , David F McDermott  8 , Christopher G Wood  5 , Toni K Choueiri  3
Affiliations
Clinical Trial

Everolimus Versus Sunitinib Prospective Evaluation in Metastatic Non-Clear Cell Renal Cell Carcinoma (ESPN): A Randomized Multicenter Phase 2 Trial

Nizar M Tannir et al. Eur Urol. 2016 May.

Abstract

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.

Keywords: Everolimus; Non–clear cell renal cell carcinoma; Renal cell carcinoma; Sunitinib.

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Figures

Fig. 1
Fig. 1
Consolidated Standards of Reporting Trials diagram. * Patient did not receive treatment in a timely manner due to delay in drug coverage by insurance.
Fig. 2
Fig. 2
(a) Progression-free survival in first-line therapy: grouping by initial treatment; (b) progression-free survival in second-line therapy. PFS = progression-free survival.
Fig. 2
Fig. 2
(a) Progression-free survival in first-line therapy: grouping by initial treatment; (b) progression-free survival in second-line therapy. PFS = progression-free survival.
Fig. 3
Fig. 3
Overall survival: grouping by initial treatment.
Fig. 4
Fig. 4
Exploratory analysis: overall survival according to the presence of sarcomatoid features regardless of treatment received in first-line therapy.
See this image and copyright information in PMC

Comment in

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