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

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• 作者：Nizar M. Tannir^a ; ^{ntannir@mdanderson.org" class="auth_mail" title="E-mail the corresponding author} ; Eric Jonasch^a ; Laurence Albiges^b ; Emre Altinmakas^c ; Chaan S. Ng^c ; Surena F. Matin^d ; Xuemei Wang^e ; Wei Qiao^e ; Zita Dubauskas Lim^a ; Pheroze Tamboli^f ; Priya Rao^f ; Kanishka Sircar^f ; Jose A. Karam^d ; David F. McDermott^g ; Christopher G. Wood^d ; Toni K. Choueiri^b
• 关键词：Renal cell carcinoma ; Non&ndash ; clear cell renal cell carcinoma ; Sunitinib ; Everolimus
• 刊名：European Urology
• 出版年：2016
• 出版时间：May 2016
• 年：2016
• 卷：69
• 期：5
• 页码：866-874
• 全文大小：1247 K

文摘

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.