Roberto Iacovelli1, Giacomo Cartenì2, Cora N Sternberg3, Michele Milella4, Matteo Santoni5, Giuseppe Di Lorenzo6, Cinzia Ortega7, Roberto Sabbatini8, Riccardo Ricotta9, Caterina Messina10, Vito Lorusso11, Francesco Atzori12, Fabio De Vincenzo13, Cosimo Sacco14, Francesco Boccardo15, Francesco Valduga16, Francesco Massari17, Valentina Baldazzi18, Saverio Cinieri19, Alessandra Mosca20, Enzo Maria Ruggeri21, Alfredo Berruti22, Linda Cerbone3, Giuseppe Procopio23. 1. Sapienza University of Rome, Department of Radiology, Oncology and Human Pathology, Rome, Italy. 2. Oncology Unit, A. Cardarelli Hospital, Naples, Italy. 3. Department of Medical Oncology, San Camillo Forlanini Hospital, Rome, Italy. 4. Medical Oncology A, Regina Elena National Cancer Institute, Rome, Italy. 5. Department of Medical Oncology, Polytechnic University of the Marche Region, Ancona, Italy. 6. Medical Oncology, Genitourinary Cancer Section, University Federico II, Naples, Italy. 7. Fondazione del Piemonte per l'Oncologia IRCC, Candiolo, Italy. 8. Oncology Division, Department of Oncology and Hematology, University of Modena e Reggio Emilia, Modena, Italy. 9. The Falck Division of Oncology, Ospedale Niguarda Ca' Granda, Milan, Italy. 10. Oncology Division, Ospedali Riuniti, Bergamo, Italy. 11. National Cancer Research Center, Istituto Tumori 'Giovanni Paolo II' Bari, Italy. 12. Medical Oncology Unit, Azienda Ospedaliero Universitaria of Cagliari, Italy. 13. Oncology and Hematology Unit, Humanitas Cancer Center, Istituto Clinico Humanitas, Rozzano, Italy. 14. Oncology Unit, St. Maria della Misericordia Hospital, Udine, Italy. 15. University and IRCCS AOU-San Martino-IST, National Cancer Research Institute, Genoa, Italy. 16. Medical Oncology, St. Chiara Hospital, Trento, Italy. 17. Medical Oncology, 'G.B. Rossi' Academic Hospital, University of Verona, Verona, Italy. 18. Department of Medical Oncology, Santa Maria Annunziata Hospital, Florence, Italy. 19. Medical Oncology & Breast Unit Department, Sen A. Perrino Hospital, Brindisi, Italy. 20. Medical Oncology, Maggiore della Carità University Hospital, Novara, Italy. 21. Oncology Unit, Belcolle Hospital, Viterbo, Italy. 22. Medical Oncology, University of Brescia, Brescia, Italy. 23. Medical Oncology Unit 1, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy. Electronic address: giuseppe.procopio@istitutotumori.mi.it.
Abstract
AIM: 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. METHODS: 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. RESULTS: 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). CONCLUSIONS: 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.
AIM: 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. METHODS: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. RESULTS: 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). CONCLUSIONS: 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.
Authors: I Duran; J Lambea; P Maroto; J L González-Larriba; Luis Flores; S Granados-Principal; M Graupera; B Sáez; A Vivancos; O Casanovas Journal: Target Oncol Date: 2017-02 Impact factor: 4.493
Authors: Christian Rothermundt; Alexandra Bailey; Linda Cerbone; Tim Eisen; Bernard Escudier; Silke Gillessen; Viktor Grünwald; James Larkin; David McDermott; Jan Oldenburg; Camillo Porta; Brian Rini; Manuela Schmidinger; Cora Sternberg; Paul M Putora Journal: Oncologist Date: 2015-08-03
Authors: Bernhard Ralla; Barbara Erber; Irena Goranova; Luise von der Aue; Anne Floercken; Stefan Hinz; Carsten Kempkensteffen; Ahmed Magheli; Kurt Miller; Jonas Busch Journal: World J Urol Date: 2015-12-16 Impact factor: 4.226
Authors: Lothar Bergmann; Ulrich Kube; Christian Doehn; Thomas Steiner; Peter J Goebell; Manfred Kindler; Edwin Herrmann; Jan Janssen; Steffen Weikert; Michael T Scheffler; Joerg Schmitz; Michael Albrecht; Michael Staehler Journal: BMC Cancer Date: 2015-04-18 Impact factor: 4.430
Authors: Michela Roberto; Maria Bassanelli; Elsa Iannicelli; Silvana Giacinti; Chiara D'Antonio; Anna Maria Aschelter; Paolo Marchetti Journal: Case Rep Oncol Med Date: 2015-12-20