First-line mammalian target of rapamycin inhibition in metastatic renal cell carcinoma: An analysis of practice patterns from the international metastatic renal cell carcinoma database consortium

Lauren C. Harshman, Nils Kroeger, Sun Young Rha, Frede Donskov, Lori Wood, Srinivas K. Tantravahi, Ulka Vaishampayan, Brian I. Rini, Jennifer Knox, Scott North, Scott Ernst, Takeshi Yuasa, Sandy Srinivas, Sumanta Pal, Daniel Y. Heng, Toni K. Choueiri

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9 Citations (Scopus)


Using an established international renal cell carcinoma (RCC) database, we retrospectively characterized the use and efficacy of mammalian target of rapamycin (mTOR) inhibitors in treatment-naive metastatic RCC (mRCC) patients. Front-line mTOR inhibitors are used in clinical practice mostly in select patients, who have non-clear cell histology, poor prognostic features, or as part of clinical trials. Introduction/Background: Approval of the mTOR inhibitors for the treatment of mRCC was based on efficacy in poor-risk patients in the first-line setting for temsirolimus and in vascular endothelial growth factor inhibitor-refractory patients for everolimus. We strove to characterize temsirolimus and everolimus use and effectiveness in the first-line setting. Patients and Methods: We performed a retrospective database analysis of mRCC patients who received mTOR inhibitors as first-line targeted therapy. The Kaplan-Meier product-limit method was used to estimate the distribution of progression-free survival (PFS) and overall survival (OS). Results: We identified 127 mRCC patients who had received a first-line mTOR inhibitor. Temsirolimus was administered in 93 patients (73%) and everolimus in 34 patients (27%). The main reasons for choice of temsirolimus were poor-risk disease (38%), non-clear cell histology (27%), and clinical trial availability (15%), whereas clinical trial (82%) and non-clear cell histology (6%) drove everolimus selection. Of the temsirolimus and everolimus patients, 58% and 32% were poor-risk according to the International mRCC Database Consortium criteria, respectively. The median PFS and OS were 3.4 and 12.5 months and 4.8 and 15.9 months with temsirolimus and everolimus, respectively. Although limited by small numbers, this study characterizes a real-world, international experience with the use of mTOR inhibition in treatment-naive mRCC patients. Conclusion: Poor-risk RCC, non-clear cell histology, and clinical trials were the predominant reasons for mTOR inhibitor selection in the front-line setting. Because of the different patient populations in which they were administered, direct comparisons of the front-line efficacy of temsirolimus and everolimus cannot be made.

Original languageEnglish
Pages (from-to)335-340
Number of pages6
JournalClinical Genitourinary Cancer
Issue number5
Publication statusPublished - 2014

Bibliographical note

Funding Information:
Lauren C. Harshman: advisory boards for Aveo, Pfizer, and Bristol-Myers Squibb, past research funding from BMS and Novartis ; Frede Donskov: research funding from Novartis ; Lori Wood: consultant (uncompensated) for Pfizer and Glaxo-Smith Kline, research funding from Pfizer , Glaxo-Smith Kline, and Novartis; Ulka Vaishampayan: consultant for Novartis, honoraria from Novartis and Pfizer , research support from Pfizer ; Brian I. Rini: consultant and research funding from Pfizer ; Jennifer Knox: consultant for Aveo, research funding from Pfizer ; Scott Ernst: consultant/advisory boards for Bristol-Myers Squib, Roche, Novartis, and Glaxo-Smith Kline; Sandy Srinivas: consultant for Pfizer, Glaxo-Smith Kline, and Genentech, research funding from Bristol-Myers Squibb , Pfizer , Glaxo-Smith Kline , and Novartis ; Sumanta Pal: honoraria from Novartis ; Daniel Y. Heng: consultant for Pfizer, Novartis, and Bayer; Toni K. Choueiri: advisory boards for Glaxo-Smith Kline, Pfizer, Novartis, Genentech, Bayer, and AVEO, research funding from Pfizer . The remaining authors have stated that they have no conflicts of interest.

Publisher Copyright:
© 2014 Elsevier Inc. All rights reserved.

All Science Journal Classification (ASJC) codes

  • Oncology
  • Urology


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