An international expanded-access programme of everolimus: Addressing safety and efficacy in patients with metastatic renal cell carcinoma who progress after initial vascular endothelial growth factor receptor-tyrosine kinase inhibitor therapy

Viktor Grünwald, Pierre I. Karakiewicz, Sevil E. Bavbek, Kurt Miller, Jean Pascal Machiels, Se Hoon Lee, James Larkin, Petri Bono, Sun Young Rha, Daniel Castellano, Christian U. Blank, Jennifer J. Knox, Robert Hawkins, Oezlem Anak, Marianne Rosamilia, Jocelyn Booth, Nicoletta Pirotta, István Bodrogi, M. Romedi, S. FerrandiniM. Rondinon, K. Pittman, D. Goldstein, J. Shapiro, S. Troon, D. Yip, P. Mainwaring, R. Zigeuner, W. Loidl, R. F. Greil, M. Schmidinger, J. De Grève, S. Rottey, J. Vermorken, J. Machiels, T. Gil, C. Gennigens, T. Roumeguere, C. Barrios, C. Mathias, H. Assi, S. Hotte, P. Karakiewicz, J. Knox, S. Spadafora, L. Wood, P. Zalewski, M. Mackensie, G. Bjarnason, A. Lalancette, A. Chan, B. Higgins, S. North, D. Soulieres, J. Asselah, C. Sperlich, W. Miller, S. Yadav, R. El-Maraghi, J. Godoy, J. Prausová, J. Katolicka, L. Petruzelka, I. Kiss, P. Bono, M. Lapela, K. Miller, L. Bergmann, J. Beck, E. Jäger, M. Kindler, F. Overkamp, M. Wirth, W. Hölzer, J. Gschwend, A. Stenzl, T. Gauler, D. Niederwieser, N. Marschner, A. Lück, H. Tessen, C. Eichelberg, T. Steiner, P. Goebell, E. Kettner, A. Bakhshandeh-Bath, M. Wilhelm, S. Schmitz, A. Jacob, S. Bierer, U. Kube, M. Staehler, E. Engel, M. Frambach, U. Schellenberger, P. Albers, J. Simon, M. Gleissler, T. Klotz, R. Repp, H. Kröning, J. Westermann, U. Rebmann, B. Brehmer, N. Niederle, C. Grund, K. Verpoort, P. Fonara, J. Rassweiler, A. Bamias, G. Fountzilas, E. Razis, D. Mouratidou, V. Georgoulias, E. Samantas, I. Bodrogi, L. Mangel, J. Szanto, R. Berger, A. Pe'er, A. Sella, R. Ben-Yosef, H. Nechushtan, L. Crinò, S. Bracarda, L. Ciuffreda, C. Graiff, A. Falcone, M. Roselli, C. Sternberg, A. Santoro, E. Ruggeri, A. Bearz, M. Venturini, M. Aglietta, D. Amadori, F. Di Costanzo, M. Bari, N. Gebbia, P. Conte, A. Bonetti, R. Bordonaro, S. Cascinu, A. Contu, G. Cruciani, D. Gasparro, M. Nardi, G. Lelli, G. Lo Re, F. Boccardo, V. Lorusso, E. Maiello, P. Manente, R. Passalacqua, F. Piantedosi, C. Porta, C. Sacco, C. Tondini, S. De Placido, G. Carteni, L. Dogliotto, G. Rosti, M. Milella, F. Roila, D. Amoroso, G. Farina, H. Al-Khatib, S. Lee, T. Kim, J. Ahn, H. Lim, S. Rha, I. Chung, J. Kim, J. Chung, M. Ghosn, A. Shameseddine, R. Lugo, P. Cabrera, S. Osanto, G. Groenewegen, C. Blank, F. van den Eertwegh, C. van Herpen, S. Oosting, P. Soetekouw, W. Lilleby, O. Klepp, T. Guren, J. Alcedo, P. Karlov, D. Nosov, L. Roman, I. Rusakov, S. Bazarbashi, C. Toh, J. Mardiak, M. Constenla, F. Garcia del Muro Solans, J. Maroto Ray, J. Bellmunt Mollins, D. Castellano, I. Duran Martinez, B. Mellado Gonzalez, M. Domenech Santasusana, M. Lopez-Brea Piqueras, J. Campillo Fuentes, J. Gonzalez Larriba, R. Luque Caro, A. Meana Garcia, L. Aparicio, N. Batista Lopez, V. Calderero Aragon, C. Valverde Morales, M. Figueiras, J. Contreras Ibanez, E. Gonzalez Billalabeitia, E. Estrada, J. Arranz, J. Lambea Sorrosal, A. Lozano, M. Codes de Villena, E. Espinosa, R. Lopez, J. Perez Garcia, A. Laurell, U. Stierner, M. Cwikiel, M. Borner, P. Y. Dietrich, C. Rothermundt, Y. Pu, Y. Chang, Y. Ou, C. Chuang, Y. Liao, V. Srimuninnimit, V. Sriuranpong, S. Buyukberber, B. Yalcin, E. Goker, S. Yalcin, T. Geldart, J. Wagstaff, S. Nicholson, S. Chowdhury, A. Bahl, R. Jones, A. Azzabi, D. Chao, K. Fife, R. Hawkins, G. Mead, P. Nathan, H. Pandha, J. Hajdenberg, N. Gabrail, N. Nimeh, T. Logan, T. Flaig, R. Schraeder, B. Rini, M. O'Rourke, C. Alemany, J. Beck, A. Kessinger, A. Amin, M. Arriaga, J. Rodriguez

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Abstract

Background and objectives: The RECORD-1 trial established the clinical benefit of everolimus in patients with metastatic renal cell carcinoma (mRCC) after failure of initial vascular endothelial growth factor receptor-tyrosine kinase inhibitor (VEGFr-TKI) therapy. The REACT (RAD001 Expanded Access Clinical Trial in RCC) study was initiated to address an unmet medical need by providing everolimus prior to commercial availability, and also to further assess the safety and efficacy of everolimus in patients with VEGFr-TKI-refractory mRCC. Patients and methods: REACT (Clinicaltrials.gov: NCT00655252) was a global, open-label, expanded-access programme in patients with mRCC who were intolerant of, or who had progressed on or after stopping treatment with, any available VEGFr-TKI therapy. Patients received everolimus 10 mg once daily, with dose and schedule modifications allowed for toxicity. Patients were closely monitored for the development of serious and grades 3/4 adverse events (AEs). Response was assessed by RECIST every 3 months for the first year and every 6 months thereafter. Results: A total of 1367 patients were enroled. Safety findings and tumour responses were consistent with those observed in RECORD-1, with no new safety issues identified. The most commonly reported serious AEs were dyspnoea (5.0%), pneumonia (4.7%) and anaemia (4.1%), and the most commonly reported grades 3/4 AEs were anaemia (13.4%), fatigue (6.7%) and dyspnoea (6.5%). Best overall response was stable disease in 51.6% and partial response in 1.7% of patients. Median everolimus treatment duration was 14 weeks. Conclusion: Everolimus is well tolerated in patients with mRCC and demonstrates a favourable risk-benefit ratio.

Original languageEnglish
Pages (from-to)324-332
Number of pages9
JournalEuropean Journal of Cancer
Volume48
Issue number3
DOIs
Publication statusPublished - febr. 1 2012

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ASJC Scopus subject areas

  • Oncology
  • Cancer Research

Cite this

Grünwald, V., Karakiewicz, P. I., Bavbek, S. E., Miller, K., Machiels, J. P., Lee, S. H., Larkin, J., Bono, P., Rha, S. Y., Castellano, D., Blank, C. U., Knox, J. J., Hawkins, R., Anak, O., Rosamilia, M., Booth, J., Pirotta, N., Bodrogi, I., Romedi, M., ... Rodriguez, J. (2012). An international expanded-access programme of everolimus: Addressing safety and efficacy in patients with metastatic renal cell carcinoma who progress after initial vascular endothelial growth factor receptor-tyrosine kinase inhibitor therapy. European Journal of Cancer, 48(3), 324-332. https://doi.org/10.1016/j.ejca.2011.06.054