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Eur J Cancer. 2013 Jun;49(9):2134-42. doi: 10.1016/j.ejca.2013.02.032. Epub 2013 Mar 18.

Clinical outcomes in patients receiving three lines of targeted therapy for metastatic renal cell carcinoma: results from a large patient cohort.

Author information

  • 1Sapienza University of Rome, Department of Radiology, Oncology and Human Pathology, Rome, Italy.
  • 2Oncology Unit, A. Cardarelli Hospital, Naples, Italy.
  • 3Department of Medical Oncology, San Camillo Forlanini Hospital, Rome, Italy.
  • 4Medical Oncology A, Regina Elena National Cancer Institute, Rome, Italy.
  • 5Department of Medical Oncology, Polytechnic University of the Marche Region, Ancona, Italy.
  • 6Medical Oncology, Genitourinary Cancer Section, University Federico II, Naples, Italy.
  • 7Fondazione del Piemonte per l'Oncologia IRCC, Candiolo, Italy.
  • 8Oncology Division, Department of Oncology and Hematology, University of Modena e Reggio Emilia, Modena, Italy.
  • 9The Falck Division of Oncology, Ospedale Niguarda Ca' Granda, Milan, Italy.
  • 10Oncology Division, Ospedali Riuniti, Bergamo, Italy.
  • 11National Cancer Research Center, Istituto Tumori 'Giovanni Paolo II' Bari, Italy.
  • 12Medical Oncology Unit, Azienda Ospedaliero Universitaria of Cagliari, Italy.
  • 13Oncology and Hematology Unit, Humanitas Cancer Center, Istituto Clinico Humanitas, Rozzano, Italy.
  • 14Oncology Unit, St. Maria della Misericordia Hospital, Udine, Italy.
  • 15University and IRCCS AOU-San Martino-IST, National Cancer Research Institute, Genoa, Italy.
  • 16Medical Oncology, St. Chiara Hospital, Trento, Italy.
  • 17Medical Oncology, 'G.B. Rossi' Academic Hospital, University of Verona, Verona, Italy.
  • 18Department of Medical Oncology, Santa Maria Annunziata Hospital, Florence, Italy.
  • 19Medical Oncology & Breast Unit Department, Sen A. Perrino Hospital, Brindisi, Italy.
  • 20Medical Oncology, Maggiore della Carità University Hospital, Novara, Italy.
  • 21Oncology Unit, Belcolle Hospital, Viterbo, Italy.
  • 22Medical Oncology, University of Brescia, Brescia, Italy.
  • 23Medical Oncology Unit 1, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy. Electronic address: giuseppe.procopio@istitutotumori.mi.it.



A number of targeted therapies (TTs) are effective in metastatic renal cell carcinoma (mRCC) but clinical outcomes with the sequential use of three TTs have been poorly investigated, this study evaluates their outcome.


Patients with clear cells mRCC treated with three TTs were retrospectively studied. Therapies were classified as vascular endothelial growth factor (VEGF)/vascular endothelial growth factor receptor (VEGFR) or mammalian target of rapamycin inhibitors (mTORi). Progression free survival (PFS), overall survival (OS) and total PFS (tPFS)--defined as the time from start of first-line to progression on third-line treatment--were estimated using the Kaplan-Meier method and curves were compared with log-rank test.


A total of 2065 patients with mRCC were consecutively treated with first-line TT in 23 centres in Italy. Overall 281/2065 patients (13%) were treated with three TTs. Median OS and tPFS were 44.7 and 34.1 months, respectively and were longer in patients receiving the sequence vascular endothelial growth factor inhibitors (VEGFi)-VEGFi-mTORi compared with those receiving VEGFi-mTORi-VEGFi with a statistical difference in OS (50.7 versus 37.8 months, p = 0.004; 36.5 versus 29.3 months, p = 0.059, respectively).


Few patients received three lines of TTs. The sequence VEGFi-VEGFi-mTORi was associated with improved survival with respect to VEGFi-mTORi-VEGFi and primary resistance to first-line was a negative predictive and prognostic factor.

Copyright © 2013 Elsevier Ltd. All rights reserved.

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