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, Theodore Logan, T. Flaig, R. Schraeder, B. Rini, M. O'Rourke, C. Alemany, J. Beck, A. Kessinger, A. Amin, M. Arriaga, J. Rodriguez

Research output: Contribution to journalArticle

76 Citations (Scopus)

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 (US)
Pages (from-to)324-332
Number of pages9
JournalEuropean Journal of Cancer
Volume48
Issue number3
DOIs
StatePublished - Feb 2012
Externally publishedYes

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Vascular Endothelial Growth Factor Receptor
Renal Cell Carcinoma
Protein-Tyrosine Kinases
Safety
Compassionate Use Trials
Therapeutics
Clinical Trials
Dyspnea
Anemia
Everolimus
Fatigue
Pneumonia
Appointments and Schedules
Odds Ratio

Keywords

  • Advanced kidney cancer
  • mTOR inhibitor
  • RAD001
  • REACT
  • Safety
  • Second-line therapy

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

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

In: European Journal of Cancer, Vol. 48, No. 3, 02.2012, p. 324-332.

Research output: Contribution to journalArticle

Grünwald, V, Karakiewicz, PI, Bavbek, SE, Miller, K, Machiels, JP, Lee, SH, Larkin, J, Bono, P, Rha, SY, Castellano, D, Blank, CU, Knox, JJ, Hawkins, R, Anak, O, Rosamilia, M, Booth, J, Pirotta, N, Bodrogi, I, Romedi, M, Ferrandini, S, Rondinon, M, Pittman, K, Goldstein, D, Shapiro, J, Troon, S, Yip, D, Mainwaring, P, Zigeuner, R, Loidl, W, Greil, RF, Schmidinger, M, De Grève, J, Rottey, S, Vermorken, J, Machiels, J, Gil, T, Gennigens, C, Roumeguere, T, Barrios, C, Mathias, C, Assi, H, Hotte, S, Karakiewicz, P, Knox, J, Spadafora, S, Wood, L, Zalewski, P, Mackensie, M, Bjarnason, G, Lalancette, A, Chan, A, Higgins, B, North, S, Soulieres, D, Asselah, J, Sperlich, C, Miller, W, Yadav, S, El-Maraghi, R, Godoy, J, Prausová, J, Katolicka, J, Petruzelka, L, Kiss, I, Bono, P, Lapela, M, Miller, K, Bergmann, L, Beck, J, Jäger, E, Kindler, M, Overkamp, F, Wirth, M, Hölzer, W, Gschwend, J, Stenzl, A, Gauler, T, Niederwieser, D, Marschner, N, Lück, A, Tessen, H, Eichelberg, C, Steiner, T, Goebell, P, Kettner, E, Bakhshandeh-Bath, A, Wilhelm, M, Schmitz, S, Jacob, A, Bierer, S, Kube, U, Staehler, M, Engel, E, Frambach, M, Schellenberger, U, Albers, P, Simon, J, Gleissler, M, Klotz, T, Repp, R, Kröning, H, Westermann, J, Rebmann, U, Brehmer, B, Niederle, N, Grund, C, Verpoort, K, Fonara, P, Rassweiler, J, Bamias, A, Fountzilas, G, Razis, E, Mouratidou, D, Georgoulias, V, Samantas, E, Bodrogi, I, Mangel, L, Szanto, J, Berger, R, Pe'er, A, Sella, A, Ben-Yosef, R, Nechushtan, H, Crinò, L, Bracarda, S, Ciuffreda, L, Graiff, C, Falcone, A, Roselli, M, Sternberg, C, Santoro, A, Ruggeri, E, Bearz, A, Venturini, M, Aglietta, M, Amadori, D, Di Costanzo, F, Bari, M, Gebbia, N, Conte, P, Bonetti, A, Bordonaro, R, Cascinu, S, Contu, A, Cruciani, G, Gasparro, D, Nardi, M, Lelli, G, Lo Re, G, Boccardo, F, Lorusso, V, Maiello, E, Manente, P, Passalacqua, R, Piantedosi, F, Porta, C, Sacco, C, Tondini, C, De Placido, S, Carteni, G, Dogliotto, L, Rosti, G, Milella, M, Roila, F, Amoroso, D, Farina, G, Al-Khatib, H, Lee, S, Kim, T, Ahn, J, Lim, H, Rha, S, Chung, I, Kim, J, Chung, J, Ghosn, M, Shameseddine, A, Lugo, R, Cabrera, P, Osanto, S, Groenewegen, G, Blank, C, van den Eertwegh, F, van Herpen, C, Oosting, S, Soetekouw, P, Lilleby, W, Klepp, O, Guren, T, Alcedo, J, Karlov, P, Nosov, D, Roman, L, Rusakov, I, Bazarbashi, S, Toh, C, Mardiak, J, Constenla, M, Solans, FGDM, Maroto Ray, J, Bellmunt Mollins, J, Castellano, D, Duran Martinez, I, Mellado Gonzalez, B, Domenech Santasusana, M, Lopez-Brea Piqueras, M, Campillo Fuentes, J, Gonzalez Larriba, J, Luque Caro, R, Meana Garcia, A, Aparicio, L, Batista Lopez, N, Calderero Aragon, V, Valverde Morales, C, Figueiras, M, Contreras Ibanez, J, Gonzalez Billalabeitia, E, Estrada, E, Arranz, J, Lambea Sorrosal, J, Lozano, A, de Villena, MC, Espinosa, E, Lopez, R, Perez Garcia, J, Laurell, A, Stierner, U, Cwikiel, M, Borner, M, Dietrich, PY, Rothermundt, C, Pu, Y, Chang, Y, Ou, Y, Chuang, C, Liao, Y, Srimuninnimit, V, Sriuranpong, V, Buyukberber, S, Yalcin, B, Goker, E, Yalcin, S, Geldart, T, Wagstaff, J, Nicholson, S, Chowdhury, S, Bahl, A, Jones, R, Azzabi, A, Chao, D, Fife, K, Hawkins, R, Mead, G, Nathan, P, Pandha, H, Hajdenberg, J, Gabrail, N, Nimeh, N, Logan, T, Flaig, T, Schraeder, R, Rini, B, O'Rourke, M, Alemany, C, Beck, J, Kessinger, A, Amin, A, Arriaga, 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, vol. 48, no. 3, pp. 324-332. https://doi.org/10.1016/j.ejca.2011.06.054
Grünwald, Viktor ; Karakiewicz, Pierre I. ; Bavbek, Sevil E. ; Miller, Kurt ; Machiels, Jean Pascal ; Lee, Se Hoon ; Larkin, James ; Bono, Petri ; Rha, Sun Young ; Castellano, Daniel ; Blank, Christian U. ; Knox, Jennifer J. ; Hawkins, Robert ; Anak, Oezlem ; Rosamilia, Marianne ; Booth, Jocelyn ; Pirotta, Nicoletta ; Bodrogi, István ; Romedi, M. ; Ferrandini, S. ; Rondinon, M. ; Pittman, K. ; Goldstein, D. ; Shapiro, J. ; Troon, S. ; Yip, D. ; Mainwaring, P. ; Zigeuner, R. ; Loidl, W. ; Greil, R. F. ; Schmidinger, M. ; De Grève, J. ; Rottey, S. ; Vermorken, J. ; Machiels, J. ; Gil, T. ; Gennigens, C. ; Roumeguere, T. ; Barrios, C. ; Mathias, C. ; Assi, H. ; Hotte, S. ; Karakiewicz, P. ; Knox, J. ; Spadafora, S. ; Wood, L. ; Zalewski, P. ; Mackensie, M. ; Bjarnason, G. ; Lalancette, A. ; Chan, A. ; Higgins, B. ; North, S. ; Soulieres, D. ; Asselah, J. ; Sperlich, C. ; Miller, W. ; Yadav, S. ; El-Maraghi, R. ; Godoy, J. ; Prausová, J. ; Katolicka, J. ; Petruzelka, L. ; Kiss, I. ; Bono, P. ; Lapela, M. ; Miller, K. ; Bergmann, L. ; Beck, J. ; Jäger, E. ; Kindler, M. ; Overkamp, F. ; Wirth, M. ; Hölzer, W. ; Gschwend, J. ; Stenzl, A. ; Gauler, T. ; Niederwieser, D. ; Marschner, N. ; Lück, A. ; Tessen, H. ; Eichelberg, C. ; Steiner, T. ; Goebell, P. ; Kettner, E. ; Bakhshandeh-Bath, A. ; Wilhelm, M. ; Schmitz, S. ; Jacob, A. ; Bierer, S. ; Kube, U. ; Staehler, M. ; Engel, E. ; Frambach, M. ; Schellenberger, U. ; Albers, P. ; Simon, J. ; Gleissler, M. ; Klotz, T. ; Repp, R. ; Kröning, H. ; Westermann, J. ; Rebmann, U. ; Brehmer, B. ; Niederle, N. ; Grund, C. ; Verpoort, K. ; Fonara, P. ; Rassweiler, J. ; Bamias, A. ; Fountzilas, G. ; Razis, E. ; Mouratidou, D. ; Georgoulias, V. ; Samantas, E. ; Bodrogi, I. ; Mangel, L. ; Szanto, J. ; Berger, R. ; Pe'er, A. ; Sella, A. ; Ben-Yosef, R. ; Nechushtan, H. ; Crinò, L. ; Bracarda, S. ; Ciuffreda, L. ; Graiff, C. ; Falcone, A. ; Roselli, M. ; Sternberg, C. ; Santoro, A. ; Ruggeri, E. ; Bearz, A. ; Venturini, M. ; Aglietta, M. ; Amadori, D. ; Di Costanzo, F. ; Bari, M. ; Gebbia, N. ; Conte, P. ; Bonetti, A. ; Bordonaro, R. ; Cascinu, S. ; Contu, A. ; Cruciani, G. ; Gasparro, D. ; Nardi, M. ; Lelli, G. ; Lo Re, G. ; Boccardo, F. ; Lorusso, V. ; Maiello, E. ; Manente, P. ; Passalacqua, R. ; Piantedosi, F. ; Porta, C. ; Sacco, C. ; Tondini, C. ; De Placido, S. ; Carteni, G. ; Dogliotto, L. ; Rosti, G. ; Milella, M. ; Roila, F. ; Amoroso, D. ; Farina, G. ; Al-Khatib, H. ; Lee, S. ; Kim, T. ; Ahn, J. ; Lim, H. ; Rha, S. ; Chung, I. ; Kim, J. ; Chung, J. ; Ghosn, M. ; Shameseddine, A. ; Lugo, R. ; Cabrera, P. ; Osanto, S. ; Groenewegen, G. ; Blank, C. ; van den Eertwegh, F. ; van Herpen, C. ; Oosting, S. ; Soetekouw, P. ; Lilleby, W. ; Klepp, O. ; Guren, T. ; Alcedo, J. ; Karlov, P. ; Nosov, D. ; Roman, L. ; Rusakov, I. ; Bazarbashi, S. ; Toh, C. ; Mardiak, J. ; Constenla, M. ; Solans, F. Garcia del Muro ; Maroto Ray, J. ; Bellmunt Mollins, J. ; Castellano, D. ; Duran Martinez, I. ; Mellado Gonzalez, B. ; Domenech Santasusana, M. ; Lopez-Brea Piqueras, M. ; Campillo Fuentes, J. ; Gonzalez Larriba, J. ; Luque Caro, R. ; Meana Garcia, A. ; Aparicio, L. ; Batista Lopez, N. ; Calderero Aragon, V. ; Valverde Morales, C. ; Figueiras, M. ; Contreras Ibanez, J. ; Gonzalez Billalabeitia, E. ; Estrada, E. ; Arranz, J. ; Lambea Sorrosal, J. ; Lozano, A. ; de Villena, M. Codes ; Espinosa, E. ; Lopez, R. ; Perez Garcia, J. ; Laurell, A. ; Stierner, U. ; Cwikiel, M. ; Borner, M. ; Dietrich, P. Y. ; Rothermundt, C. ; Pu, Y. ; Chang, Y. ; Ou, Y. ; Chuang, C. ; Liao, Y. ; Srimuninnimit, V. ; Sriuranpong, V. ; Buyukberber, S. ; Yalcin, B. ; Goker, E. ; Yalcin, S. ; Geldart, T. ; Wagstaff, J. ; Nicholson, S. ; Chowdhury, S. ; Bahl, A. ; Jones, R. ; Azzabi, A. ; Chao, D. ; Fife, K. ; Hawkins, R. ; Mead, G. ; Nathan, P. ; Pandha, H. ; Hajdenberg, J. ; Gabrail, N. ; Nimeh, N. ; Logan, Theodore ; Flaig, T. ; Schraeder, R. ; Rini, B. ; O'Rourke, M. ; Alemany, C. ; Beck, J. ; Kessinger, A. ; Amin, A. ; Arriaga, M. ; Rodriguez, J. / 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. In: European Journal of Cancer. 2012 ; Vol. 48, No. 3. pp. 324-332.
@article{a6dd661c4ea84750805c4d5601a53022,
title = "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",
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.",
keywords = "Advanced kidney cancer, mTOR inhibitor, RAD001, REACT, Safety, Second-line therapy",
author = "Viktor Gr{\"u}nwald and Karakiewicz, {Pierre I.} and Bavbek, {Sevil E.} and Kurt Miller and Machiels, {Jean Pascal} and Lee, {Se Hoon} and James Larkin and Petri Bono and Rha, {Sun Young} and Daniel Castellano and Blank, {Christian U.} and Knox, {Jennifer J.} and Robert Hawkins and Oezlem Anak and Marianne Rosamilia and Jocelyn Booth and Nicoletta Pirotta and Istv{\'a}n Bodrogi and M. Romedi and S. Ferrandini and M. Rondinon and K. Pittman and D. Goldstein and J. Shapiro and S. Troon and D. Yip and P. Mainwaring and R. Zigeuner and W. Loidl and Greil, {R. F.} and M. Schmidinger and {De Gr{\`e}ve}, J. and S. Rottey and J. Vermorken and J. Machiels and T. Gil and C. Gennigens and T. Roumeguere and C. Barrios and C. Mathias and H. Assi and S. Hotte and P. Karakiewicz and J. Knox and S. Spadafora and L. Wood and P. Zalewski and M. Mackensie and G. Bjarnason and A. Lalancette and A. Chan and B. Higgins and S. North and D. Soulieres and J. Asselah and C. Sperlich and W. Miller and S. Yadav and R. El-Maraghi and J. Godoy and J. Prausov{\'a} and J. Katolicka and L. Petruzelka and I. Kiss and P. Bono and M. Lapela and K. Miller and L. Bergmann and J. Beck and E. J{\"a}ger and M. Kindler and F. Overkamp and M. Wirth and W. H{\"o}lzer and J. Gschwend and A. Stenzl and T. Gauler and D. Niederwieser and N. Marschner and A. L{\"u}ck and H. Tessen and C. Eichelberg and T. Steiner and P. Goebell and E. Kettner and A. Bakhshandeh-Bath and M. Wilhelm and S. Schmitz and A. Jacob and S. Bierer and U. Kube and M. Staehler and E. Engel and M. Frambach and U. Schellenberger and P. Albers and J. Simon and M. Gleissler and T. Klotz and R. Repp and H. Kr{\"o}ning and J. Westermann and U. Rebmann and B. Brehmer and N. Niederle and C. Grund and K. Verpoort and P. Fonara and J. Rassweiler and A. Bamias and G. Fountzilas and E. Razis and D. Mouratidou and V. Georgoulias and E. Samantas and I. Bodrogi and L. Mangel and J. Szanto and R. Berger and A. Pe'er and A. Sella and R. Ben-Yosef and H. Nechushtan and L. Crin{\`o} and S. Bracarda and L. Ciuffreda and C. Graiff and A. Falcone and M. Roselli and C. Sternberg and A. Santoro and E. Ruggeri and A. Bearz and M. Venturini and M. Aglietta and D. Amadori and {Di Costanzo}, F. and M. Bari and N. Gebbia and P. Conte and A. Bonetti and R. Bordonaro and S. Cascinu and A. Contu and G. Cruciani and D. Gasparro and M. Nardi and G. Lelli and {Lo Re}, G. and F. Boccardo and V. Lorusso and E. Maiello and P. Manente and R. Passalacqua and F. Piantedosi and C. Porta and C. Sacco and C. Tondini and {De Placido}, S. and G. Carteni and L. Dogliotto and G. Rosti and M. Milella and F. Roila and D. Amoroso and G. Farina and H. Al-Khatib and S. Lee and T. Kim and J. Ahn and H. Lim and S. Rha and I. Chung and J. Kim and J. Chung and M. Ghosn and A. Shameseddine and R. Lugo and P. Cabrera and S. Osanto and G. Groenewegen and C. Blank and {van den Eertwegh}, F. and {van Herpen}, C. and S. Oosting and P. Soetekouw and W. Lilleby and O. Klepp and T. Guren and J. Alcedo and P. Karlov and D. Nosov and L. Roman and I. Rusakov and S. Bazarbashi and C. Toh and J. Mardiak and M. Constenla and Solans, {F. Garcia del Muro} and {Maroto Ray}, J. and {Bellmunt Mollins}, J. and D. Castellano and {Duran Martinez}, I. and {Mellado Gonzalez}, B. and {Domenech Santasusana}, M. and {Lopez-Brea Piqueras}, M. and {Campillo Fuentes}, J. and {Gonzalez Larriba}, J. and {Luque Caro}, R. and {Meana Garcia}, A. and L. Aparicio and {Batista Lopez}, N. and {Calderero Aragon}, V. and {Valverde Morales}, C. and M. Figueiras and {Contreras Ibanez}, J. and {Gonzalez Billalabeitia}, E. and E. Estrada and J. Arranz and {Lambea Sorrosal}, J. and A. Lozano and {de Villena}, {M. Codes} and E. Espinosa and R. Lopez and {Perez Garcia}, J. and A. Laurell and U. Stierner and M. Cwikiel and M. Borner and Dietrich, {P. Y.} and C. Rothermundt and Y. Pu and Y. Chang and Y. Ou and C. Chuang and Y. Liao and V. Srimuninnimit and V. Sriuranpong and S. Buyukberber and B. Yalcin and E. Goker and S. Yalcin and T. Geldart and J. Wagstaff and S. Nicholson and S. Chowdhury and A. Bahl and R. Jones and A. Azzabi and D. Chao and K. Fife and R. Hawkins and G. Mead and P. Nathan and H. Pandha and J. Hajdenberg and N. Gabrail and N. Nimeh and Theodore Logan and T. Flaig and R. Schraeder and B. Rini and M. O'Rourke and C. Alemany and J. Beck and A. Kessinger and A. Amin and M. Arriaga and J. Rodriguez",
year = "2012",
month = "2",
doi = "10.1016/j.ejca.2011.06.054",
language = "English (US)",
volume = "48",
pages = "324--332",
journal = "European Journal of Cancer",
issn = "0959-8049",
publisher = "Elsevier Limited",
number = "3",

}

TY - JOUR

T1 - An international expanded-access programme of everolimus

T2 - Addressing safety and efficacy in patients with metastatic renal cell carcinoma who progress after initial vascular endothelial growth factor receptor-tyrosine kinase inhibitor therapy

AU - Grünwald, Viktor

AU - Karakiewicz, Pierre I.

AU - Bavbek, Sevil E.

AU - Miller, Kurt

AU - Machiels, Jean Pascal

AU - Lee, Se Hoon

AU - Larkin, James

AU - Bono, Petri

AU - Rha, Sun Young

AU - Castellano, Daniel

AU - Blank, Christian U.

AU - Knox, Jennifer J.

AU - Hawkins, Robert

AU - Anak, Oezlem

AU - Rosamilia, Marianne

AU - Booth, Jocelyn

AU - Pirotta, Nicoletta

AU - Bodrogi, István

AU - Romedi, M.

AU - Ferrandini, S.

AU - Rondinon, M.

AU - Pittman, K.

AU - Goldstein, D.

AU - Shapiro, J.

AU - Troon, S.

AU - Yip, D.

AU - Mainwaring, P.

AU - Zigeuner, R.

AU - Loidl, W.

AU - Greil, R. F.

AU - Schmidinger, M.

AU - De Grève, J.

AU - Rottey, S.

AU - Vermorken, J.

AU - Machiels, J.

AU - Gil, T.

AU - Gennigens, C.

AU - Roumeguere, T.

AU - Barrios, C.

AU - Mathias, C.

AU - Assi, H.

AU - Hotte, S.

AU - Karakiewicz, P.

AU - Knox, J.

AU - Spadafora, S.

AU - Wood, L.

AU - Zalewski, P.

AU - Mackensie, M.

AU - Bjarnason, G.

AU - Lalancette, A.

AU - Chan, A.

AU - Higgins, B.

AU - North, S.

AU - Soulieres, D.

AU - Asselah, J.

AU - Sperlich, C.

AU - Miller, W.

AU - Yadav, S.

AU - El-Maraghi, R.

AU - Godoy, J.

AU - Prausová, J.

AU - Katolicka, J.

AU - Petruzelka, L.

AU - Kiss, I.

AU - Bono, P.

AU - Lapela, M.

AU - Miller, K.

AU - Bergmann, L.

AU - Beck, J.

AU - Jäger, E.

AU - Kindler, M.

AU - Overkamp, F.

AU - Wirth, M.

AU - Hölzer, W.

AU - Gschwend, J.

AU - Stenzl, A.

AU - Gauler, T.

AU - Niederwieser, D.

AU - Marschner, N.

AU - Lück, A.

AU - Tessen, H.

AU - Eichelberg, C.

AU - Steiner, T.

AU - Goebell, P.

AU - Kettner, E.

AU - Bakhshandeh-Bath, A.

AU - Wilhelm, M.

AU - Schmitz, S.

AU - Jacob, A.

AU - Bierer, S.

AU - Kube, U.

AU - Staehler, M.

AU - Engel, E.

AU - Frambach, M.

AU - Schellenberger, U.

AU - Albers, P.

AU - Simon, J.

AU - Gleissler, M.

AU - Klotz, T.

AU - Repp, R.

AU - Kröning, H.

AU - Westermann, J.

AU - Rebmann, U.

AU - Brehmer, B.

AU - Niederle, N.

AU - Grund, C.

AU - Verpoort, K.

AU - Fonara, P.

AU - Rassweiler, J.

AU - Bamias, A.

AU - Fountzilas, G.

AU - Razis, E.

AU - Mouratidou, D.

AU - Georgoulias, V.

AU - Samantas, E.

AU - Bodrogi, I.

AU - Mangel, L.

AU - Szanto, J.

AU - Berger, R.

AU - Pe'er, A.

AU - Sella, A.

AU - Ben-Yosef, R.

AU - Nechushtan, H.

AU - Crinò, L.

AU - Bracarda, S.

AU - Ciuffreda, L.

AU - Graiff, C.

AU - Falcone, A.

AU - Roselli, M.

AU - Sternberg, C.

AU - Santoro, A.

AU - Ruggeri, E.

AU - Bearz, A.

AU - Venturini, M.

AU - Aglietta, M.

AU - Amadori, D.

AU - Di Costanzo, F.

AU - Bari, M.

AU - Gebbia, N.

AU - Conte, P.

AU - Bonetti, A.

AU - Bordonaro, R.

AU - Cascinu, S.

AU - Contu, A.

AU - Cruciani, G.

AU - Gasparro, D.

AU - Nardi, M.

AU - Lelli, G.

AU - Lo Re, G.

AU - Boccardo, F.

AU - Lorusso, V.

AU - Maiello, E.

AU - Manente, P.

AU - Passalacqua, R.

AU - Piantedosi, F.

AU - Porta, C.

AU - Sacco, C.

AU - Tondini, C.

AU - De Placido, S.

AU - Carteni, G.

AU - Dogliotto, L.

AU - Rosti, G.

AU - Milella, M.

AU - Roila, F.

AU - Amoroso, D.

AU - Farina, G.

AU - Al-Khatib, H.

AU - Lee, S.

AU - Kim, T.

AU - Ahn, J.

AU - Lim, H.

AU - Rha, S.

AU - Chung, I.

AU - Kim, J.

AU - Chung, J.

AU - Ghosn, M.

AU - Shameseddine, A.

AU - Lugo, R.

AU - Cabrera, P.

AU - Osanto, S.

AU - Groenewegen, G.

AU - Blank, C.

AU - van den Eertwegh, F.

AU - van Herpen, C.

AU - Oosting, S.

AU - Soetekouw, P.

AU - Lilleby, W.

AU - Klepp, O.

AU - Guren, T.

AU - Alcedo, J.

AU - Karlov, P.

AU - Nosov, D.

AU - Roman, L.

AU - Rusakov, I.

AU - Bazarbashi, S.

AU - Toh, C.

AU - Mardiak, J.

AU - Constenla, M.

AU - Solans, F. Garcia del Muro

AU - Maroto Ray, J.

AU - Bellmunt Mollins, J.

AU - Castellano, D.

AU - Duran Martinez, I.

AU - Mellado Gonzalez, B.

AU - Domenech Santasusana, M.

AU - Lopez-Brea Piqueras, M.

AU - Campillo Fuentes, J.

AU - Gonzalez Larriba, J.

AU - Luque Caro, R.

AU - Meana Garcia, A.

AU - Aparicio, L.

AU - Batista Lopez, N.

AU - Calderero Aragon, V.

AU - Valverde Morales, C.

AU - Figueiras, M.

AU - Contreras Ibanez, J.

AU - Gonzalez Billalabeitia, E.

AU - Estrada, E.

AU - Arranz, J.

AU - Lambea Sorrosal, J.

AU - Lozano, A.

AU - de Villena, M. Codes

AU - Espinosa, E.

AU - Lopez, R.

AU - Perez Garcia, J.

AU - Laurell, A.

AU - Stierner, U.

AU - Cwikiel, M.

AU - Borner, M.

AU - Dietrich, P. Y.

AU - Rothermundt, C.

AU - Pu, Y.

AU - Chang, Y.

AU - Ou, Y.

AU - Chuang, C.

AU - Liao, Y.

AU - Srimuninnimit, V.

AU - Sriuranpong, V.

AU - Buyukberber, S.

AU - Yalcin, B.

AU - Goker, E.

AU - Yalcin, S.

AU - Geldart, T.

AU - Wagstaff, J.

AU - Nicholson, S.

AU - Chowdhury, S.

AU - Bahl, A.

AU - Jones, R.

AU - Azzabi, A.

AU - Chao, D.

AU - Fife, K.

AU - Hawkins, R.

AU - Mead, G.

AU - Nathan, P.

AU - Pandha, H.

AU - Hajdenberg, J.

AU - Gabrail, N.

AU - Nimeh, N.

AU - Logan, Theodore

AU - Flaig, T.

AU - Schraeder, R.

AU - Rini, B.

AU - O'Rourke, M.

AU - Alemany, C.

AU - Beck, J.

AU - Kessinger, A.

AU - Amin, A.

AU - Arriaga, M.

AU - Rodriguez, J.

PY - 2012/2

Y1 - 2012/2

N2 - 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.

AB - 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.

KW - Advanced kidney cancer

KW - mTOR inhibitor

KW - RAD001

KW - REACT

KW - Safety

KW - Second-line therapy

UR - http://www.scopus.com/inward/record.url?scp=84856225907&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84856225907&partnerID=8YFLogxK

U2 - 10.1016/j.ejca.2011.06.054

DO - 10.1016/j.ejca.2011.06.054

M3 - Article

C2 - 21803569

AN - SCOPUS:84856225907

VL - 48

SP - 324

EP - 332

JO - European Journal of Cancer

JF - European Journal of Cancer

SN - 0959-8049

IS - 3

ER -