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 language | English |
|---|---|
| Pages (from-to) | 324-332 |
| Number of pages | 9 |
| Journal | European Journal of Cancer |
| Volume | 48 |
| Issue number | 3 |
| DOIs | |
| State | Published - Feb 2012 |
Keywords
- Advanced kidney cancer
- RAD001
- REACT
- Safety
- Second-line therapy
- mTOR inhibitor
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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, T.; 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 journal › Article › peer-review
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, T.
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.
N1 - Funding Information: This work was supported by Novartis Pharmaceuticals Corporation. Novartis-affiliated authors had a role in formulating the study concepts and design, coordinating data acquisition, performing quality control, data analysis and interpretation and statistical analysis, and editing and reviewing the manuscript. All authors participated in the decision to submit this manuscript for publication.
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 - RAD001
KW - REACT
KW - Safety
KW - Second-line therapy
KW - mTOR inhibitor
UR - http://www.scopus.com/inward/record.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 -