title: Pazopanib in Metastatic Renal Cancer: A "Real-World" Experience at National Cancer Institute "Fondazione G. Pascale".
abstract: Pazopanib is an oral angiogenesis inhibitor, currently approved for treatment of metastatic renal cell carcinoma (mRCC) and soft tissue sarcoma. The present study analyzed the outcomes of pazopanib in first-line treatment of mRCC, in a single Italian cancer center. In the light of the retrospective, observational nature and the unselected population, our experience can be defined a "real-world" study. The medical records of 38 mRCC patients treated with front-line pazopanib were retrospectively reviewed and analyzed. The progression free survival (PFS) and the overall survival (OS) were the primary endpoints, while secondary objectives included objective response rate (ORR), disease control rate (DCR), and treatment tolerability. Pazopanib achieved a median PFS (mPFS) of 12.7 months (95% CI, 6.9-18.5 months). The median OS (mOS) was 26.2 months (95% CI, 12.6-39.9 months); the observed ORR and DCR were 30.3 and 72.7%, respectively, with a median duration of response of 11 weeks. mPFS appeared not to be influenced by number of co-morbidities (< 3 vs. ≥3), gender, Fuhrman grade and age. Conversely, the ORR and the DCR positively affect the mPFS (HR = 0.05 [95% CI, 0.05-0.55], p = 0.01; HR = 0.10 [95% CI, 0.02-0.43], p = 0.002, respectively). A worse outcome was associated with a lower mPFS in patients with liver metastases (p = 0.2) and with a high tumor burden (number of metastatic sites < 6 vs. ≥6) (p = 0.08). Worst OS was observed in patients aged ≥70 years old (HR = 6.91 [95% CI, 1.49-31.91], p = 0.01). The treatment was well-tolerated: no grade 4 adverse events, nor discontinuation due to toxicities was reported. Grade 3 hypertension affected positively the OS reaching the statistical significance (HR = 0.22 [95% CI, 0.05-0.8], p = 0.03). Thyroid dysfunction (hypo and hyperthyroidism) seems to correlate with better outcome in terms of a longer mPFS (HR = 0.12 [95% CI, 0.02-0.78], p = 0.02). Our results are consistent with those reported in prospective phase III trials and the published retrospective "real world" experiences. This analysis confirms the safety and efficacy of pazopanib in first-line setting, both in frail patients with multiple co-morbidities and Karnofsky PS < 80% and in younger, healthier patients with a number of metastatic sites < 6.
authors.affiliation: Division of Medical Oncology, Department of Uro-Gynaecological Oncology, Istituto Nazionale Tumori IRCCS "Fondazione G. Pascale," Naples, Italy.
authors.forename: Sabrina C
authors.initials: SC
authors.lastname: Cecere
authors.affiliation: Division of Medical Oncology, Department of Uro-Gynaecological Oncology, Istituto Nazionale Tumori IRCCS "Fondazione G. Pascale," Naples, Italy.
authors.forename: Sabrina
authors.initials: S
authors.lastname: Rossetti
authors.affiliation: Department of Onco-Ematology Medical Oncology, S.G. Moscati Hospital of Taranto Taranto, Italy.
authors.forename: Carla
authors.initials: C
authors.lastname: Cavaliere
authors.affiliation: Division of Medical Oncology, Department of Uro-Gynaecological Oncology, Istituto Nazionale Tumori IRCCS "Fondazione G. Pascale," Naples, Italy.
authors.forename: Chiara
authors.initials: C
authors.lastname: Della Pepa
authors.affiliation: Division of Medical Oncology, Department of Uro-Gynaecological Oncology, Istituto Nazionale Tumori IRCCS "Fondazione G. Pascale," Naples, Italy.
authors.forename: Marilena
authors.initials: M
authors.lastname: Di Napoli
authors.affiliation: Unit of Epidemiology, Struttura Complessa di Statistica Medica, Biometria e Bioinformatica, Istituto Nazionale Tumori IRCCS "Fondazione G. Pascale," Naples, Italy.
authors.forename: Anna
authors.initials: A
authors.lastname: Crispo
authors.affiliation: Division of Medical Oncology, Department of Uro-Gynaecological Oncology, Istituto Nazionale Tumori IRCCS "Fondazione G. Pascale," Naples, Italy.
authors.forename: Gelsomina
authors.initials: G
authors.lastname: Iovane
authors.affiliation: Pharmacy Unit, Istituto Nazionale Tumori IRCCS "Fondazione G. Pascale," Naples, Italy.
authors.forename: Raffaele
authors.initials: R
authors.lastname: Piscitelli
authors.affiliation: Division of Urology, Department of Uro-Gynaecological Oncology, Istituto Nazionale Tumori IRCCS "Fondazione G. Pascale," Naples, Italy.
authors.forename: Domenico
authors.initials: D
authors.lastname: Sorrentino
authors.affiliation: Scientific Direction, Istituto Nazionale Tumori IRCCS "Fondazione G. Pascale," Naples, Italy.
authors.forename: Gennaro
authors.initials: G
authors.lastname: Ciliberto
authors.affiliation: Pharmacy Unit, Istituto Nazionale Tumori IRCCS "Fondazione G. Pascale," Naples, Italy.
authors.forename: Piera
authors.initials: P
authors.lastname: Maiolino
authors.affiliation: Division of Radiation Oncology, Istituto Nazionale Tumori IRCCS "Fondazione G. Pascale," Naples, Italy.
authors.forename: Paolo
authors.initials: P
authors.lastname: Muto
authors.affiliation: Division of Urology, Department of Uro-Gynaecological Oncology, Istituto Nazionale Tumori IRCCS "Fondazione G. Pascale," Naples, Italy.
authors.forename: Sisto
authors.initials: S
authors.lastname: Perdonà
authors.affiliation: Division of Medical Oncology-Centro di Riferimento Oncologico Aviano, Italy.
authors.forename: Massimiliano
authors.initials: M
authors.lastname: Berretta
authors.affiliation: Division of Medical Oncology, Department of Uro-Gynaecological Oncology, Istituto Nazionale Tumori IRCCS "Fondazione G. Pascale," Naples, Italy.
authors.forename: Sandro
authors.initials: S
authors.lastname: Pignata
authors.affiliation: Division of Medical Oncology, Department of Uro-Gynaecological Oncology, Istituto Nazionale Tumori IRCCS "Fondazione G. Pascale," Naples, Italy.
authors.forename: Gaetano
authors.initials: G
authors.lastname: Facchini
authors.affiliation: Oncology Unit, A.O.R.N. dei COLLI "Ospedali Monaldi-Cotugno-CTO," Naples, Italy.
authors.forename: Carmine
authors.initials: C
authors.lastname: D'Aniello
keywords: PFS; first-line; mRCC; pazopanib; real-life