Roberto Iacovelli1, Maria Cossu Rocca2, Luca Galli3, Ugo De Giorgi4, Roberto Sabbatini5, Matteo Santoni6, Alessandra Mosca7, Giuseppe Fornarini8, Francesco Massari9, Cristina Masini10, Melissa Bersanelli11, Elisa Biasco3, Cristian Lolli4, Annalisa Guida5, Rossana Berardi6, Carlo Terrone12, Alessandro Pastorino8, Andrea Ardizzoni9, Carmine Pinto10, Sebastiano Buti12, Franco Nolè2, Giampaolo Tortora13. 1. Department of Medicine, Medical Oncology Unit, Azienda Ospedaliera Universitaria Integrata (AOUI), Verona, Italy. Electronic address: roberto.iacovelli@aovr.veneto.it. 2. Medical Oncology Division of Urogenital and Head and Neck Tumours, European Institute of Oncology, Milan, Italy. 3. Department of Medicine and Oncology, Medical Oncology 2, AOUP, Istituto Toscano Tumori, Pisa, Italy. 4. Department of Medical Oncology, Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori (IRST) IRCCS, Meldola, Italy. 5. Departmet of Oncology and Haematology and Respiratory Disease, University Hospital, Modena, Italy. 6. Medical Oncology, Università Politecnica delle Marche, Azienda Ospedaliero-Universitaria Ospedali Riuniti Umberto I, Ancona, Italy. 7. Department of Translational Medicine, Medical Oncology, Maggiore della Carità Academic Hospital, University of Eastern Piedmont, Novara, Italy. 8. Medical Oncology Department, IRCCS Azienda Ospedaliera Universitaria San Martino-IST Istituto Nazionale per la Ricerca sul Cancro, Genova, Italy. 9. Division of Oncology, S.Orsola-Malpighi Hospital, Bologna, Italy. 10. Department of Oncology and Advanced Technology, Medical Oncology Unit, Arcispedale Santa Maria Nuova, IRCCS, Reggio Emilia, Italy. 11. Dipartimento di Emergenza-Urgenza e Area medica generale e Specialistica, Medical Oncology Unit, University Hospital of Parma, Parma, Italy. 12. Department of Translational Medicine, Urology, Maggiore della Carità Academic Hospital, University of Eastern Piedmont, Novara, Italy. 13. Department of Medicine, Medical Oncology Unit, Azienda Ospedaliera Universitaria Integrata (AOUI), Verona, Italy.
Abstract
OBJECTIVES: To investigate the different outcomes in patients with metastatic renal cell carcinoma (mRCC) who receive a reduced first-line dose of sunitinib or pazopanib compared to those who continue at the standard dose. PATIENTS AND METHODS: All the patients treated in 11 oncological centers in Italy for mRCC who started first-line treatment with sunitinib or pazopanib at the standard dose. Descriptive statistical tests were used to highlight differences among groups. Survival was estimated by the Kaplan-Meier method and compared across the groups using log-rank tests, the Cox proportional hazards model adjusted for statistically significant variables was also done. RESULTS: A total of 591 patients were included in the study. Of these, 45.7% received a reduced dose of sunitinib or pazopanib after a median treatment time of 3.6 months at the standard dose. The median overall survival in the patients who continued to receive the standard dose was 24.0 months compared to 49.4 months for those who received a reduced dose (hazard ratio = 1.80; 95% CI: 1.42-2.29; P<0.001). Only 45% of the patients received second-line therapy: 42.5% had an mTOR and 54.1% a tyrosine kinase inhibitor. Second-line overall survival was 19.8 and 11.8 months, respectively, in the patients who received, or did not, a reduced dose during first-line therapy (P = 0.007). CONCLUSIONS: Toxicity-related dose reduction is a common event in mRCC patients who have started first-line therapy with either sunitinib or pazopanib. This is positively related to the outcomes of both first- and second-line therapy.
OBJECTIVES: To investigate the different outcomes in patients with metastatic renal cell carcinoma (mRCC) who receive a reduced first-line dose of sunitinib or pazopanib compared to those who continue at the standard dose. PATIENTS AND METHODS: All the patients treated in 11 oncological centers in Italy for mRCC who started first-line treatment with sunitinib or pazopanib at the standard dose. Descriptive statistical tests were used to highlight differences among groups. Survival was estimated by the Kaplan-Meier method and compared across the groups using log-rank tests, the Cox proportional hazards model adjusted for statistically significant variables was also done. RESULTS: A total of 591 patients were included in the study. Of these, 45.7% received a reduced dose of sunitinib or pazopanib after a median treatment time of 3.6 months at the standard dose. The median overall survival in the patients who continued to receive the standard dose was 24.0 months compared to 49.4 months for those who received a reduced dose (hazard ratio = 1.80; 95% CI: 1.42-2.29; P<0.001). Only 45% of the patients received second-line therapy: 42.5% had an mTOR and 54.1% a tyrosine kinase inhibitor. Second-line overall survival was 19.8 and 11.8 months, respectively, in the patients who received, or did not, a reduced dose during first-line therapy (P = 0.007). CONCLUSIONS: Toxicity-related dose reduction is a common event in mRCC patients who have started first-line therapy with either sunitinib or pazopanib. This is positively related to the outcomes of both first- and second-line therapy.