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

Sunitinib and everolimus are standard first-line and second-line therapies, respectively, in clear cell renal cell carcinoma (ccRCC).

To conduct a randomized phase 2 trial comparing sunitinib and everolimus in non-clear cell RCC (non-ccRCC).

Patients with metastatic, non-ccRCC, or ccRCC with >20% sarcomatoid features (ccSRCC) were randomized to receive sunitinib or everolimus with crossover at disease progression.

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.

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.

In this trial, everolimus was not superior to sunitinib. Both agents demonstrated modest efficacy, underscoring the need for better therapies in non-ccRCC.

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.

European urology. 2015 Nov 25 [Epub ahead of print]

Nizar M Tannir, Eric Jonasch, Laurence Albiges, Emre Altinmakas, Chaan S Ng, Surena F Matin, Xuemei Wang, Wei Qiao, Zita Dubauskas Lim, Pheroze Tamboli, Priya Rao, Kanishka Sircar, Jose A Karam, David F McDermott, Christopher G Wood, Toni K Choueiri

Department of Genitourinary Medical Oncology, Division of Cancer Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.  Department of Genitourinary Medical Oncology, Division of Cancer Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX, USA. , Dana-Farber Cancer Institute/Harvard Medical School, Boston, MA, USA. , Diagnostic Radiology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA. , Diagnostic Radiology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA. , Department of Urology, Division of Surgery, The University of Texas MD Anderson Cancer Center, Houston, TX, USA. , Department of Biostatistics, The University of Texas MD Anderson Cancer Center, Houston, TX, USA. , Department of Biostatistics, The University of Texas MD Anderson Cancer Center, Houston, TX, USA. , Department of Genitourinary Medical Oncology, Division of Cancer Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX, USA. , Pathology Department, The University of Texas MD Anderson Cancer Center, Houston, TX, USA. , Pathology Department, The University of Texas MD Anderson Cancer Center, Houston, TX, USA. , Pathology Department, The University of Texas MD Anderson Cancer Center, Houston, TX, USA. , Department of Urology, Division of Surgery, The University of Texas MD Anderson Cancer Center, Houston, TX, USA. , Beth-Israel Deaconess Medical Center, Boston, MA, USA. , Department of Urology, Division of Surgery, The University of Texas MD Anderson Cancer Center, Houston, TX, USA. , Dana-Farber Cancer Institute/Harvard Medical School, Boston, MA, USA.

PubMed

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