Fondazione IRCCS Istituto Nazionale Tumori Research Articles

873 - Could the Safety Profile of Everolimus be Different in Different Cancers? Fondazione IRCCS Istituto Nazionale Tumori (INT) Experience in Renal Cell Carcinoma, Neuroendocrine Tumors (NETS) and Biliary-Tract Cancers

ABSTRACT Background Everolimus is an inhibitor of the mammalian target of rapamycin (mTOR), a kinase which plays a key role in cellular processes. The toxicity profile of antiangiogenic therapies lacks disease specificity; while few data on everolimus are available. Methods We retrospectively analyzed data about safety profile of everolimus in patients (pts) with different cancer treated in our Institution: 21 pts with metastatic renal cell cancer (mRCC), 20 pts with biliary tract cancer, 12 pts with pancreatic neuroendocrine tumors (NETs). All were pre-treated with 1 standard treatment (Tirosine Kinase Inhibitors/chemotherapy/somatostatine analogs +/- chemotherapy, respectively) at least and received everolimus at 10 mg od continuously. Results mRCC pts: median age 64 years (53-78), median treatment exposure 6.8 months (3-20); previous treatments (1/2/3:28%/47%/23% respectively) AEs: mucositis (68%, 1 pt G3), hypertriglyceridemia (56%; 20% G3), hypercholesterolemia (43%, 1 pt G3), rash (31% 1 pt G3), pneumonitis (10% all G1), no haematological AEs Biliary tract cancer pts: median age 61 years (48-74), median treatment exposure 4.6 months (2-10), previous treatments (1/2: 85%/15% respectively) AEs: thrombocytopenia (60%, 3 pts G3), fatigue (30%, 2 pts G3), mucositis (25% no G3), 20% rash (no G3) NETs pts: median age 57(38-76), median treatment exposure 8.1 months (3-12); previous treatments (1/2:45%/55% respectively) AEs: 60% fatigue (2 pts G3), neutropenia 35% (1 pt G3), mucositis 25% (no G3), 12% rash (no G3), thrombocytopenia 15% (no G3), hypercholesterolemia 12% (no G3), hypertriglyceridemia 8% (no G3) Dose reductions from 10 mg to 5 mg: 26% in mRCC, 27% in biliary cancers, 25% in NETs Drug interruptions( Conclusions Everolimus is safe and well tolerated. AEs seem to be maintained across the different baseline disease. However the differences in the frequencies of the same AEs observed suggest a potential impact of previous treatment on Everolimus tolerability. May be interesting to study the inter-individual and the oncotype variability of everolimus in terms of different activities of the drug efflux pump P-glycoprotein. Moreover the metabolism of cytochrome P450 and the polymorphism in his gene could be further investigated. Disclosure All authors have declared no conflicts of interest.

Prognostic factors for survival in patients with metastatic renal cell carcinoma (mRCC) treated with antiangiogenic therapies: Overall results of a large experience.

e15026 Background: While the most important prognostic factors for mRCC have been evaluated in the cytokines era, only limited data and evidences are available to correlate and validate the role of prognostic factors with the use of targeted therapies (TT).(Heng 2009). This study was performed to assess the role of prognostic factors in mRCC treated with TT. Methods: From Dec 2004 to Jun 2010 baseline characteristics and outcomes of 310 consecutive patients affected by mRCC and receiving TT were collected from the database of Fondazione IRCCS Istituto Nazionale Tumori of Milan, Italy. The main characteristics of patients were: ECOG PS 0/1/2 168(54%)/123 (40%)/19(6%); sex M/F 229 (74%)/81 (26%); clear-cell histology 268 (86%)/non clear-cell 42 (14%); previous nephrectomy 273 (88%); Fuhrman grade 1/2/3/4 15 (6%)/93 (34%)/118 (44%)/43 (16%).The Fuhrman grade was unspecified in 41 pts (13%). According to Motzer criteria 100 cases (32%) were classified as low risk, 146 (47%) as intermediate risk and 64 (21%) as poor prognosis. One hundred sixty three (53%) patients received only one TT while 113 (36%), 30 (10%) and 4 (1%) received 2, 3 and 4 TT, respectively. Overall 233 (75%) patients received sorafenib, 172 (55%) sunitinib, 32 (10%) a bevacizumab regimen and 20 (7%) other TT. The uni- and multi-variate analyses were done by Cox proportional hazard regression analysis. Results: After a median follow-up of 37 months, 179 patients (57%) had died. The median overall survival (OS) was 22 months and the 5- year OS was 23.4% (95% CI:16.7-30.0). The Motzer criteria were validated as prognostic factors in the uni- and multi-variate analysis (p<001). The median and 5-year OS was 43 months and 42.8% in low risk patients, 21 months and 15.9% in the intermediate risk and 8 months in poor risk. In the univariate analysis nephrectomy, ECOG PS, number of sites of disease and Fuhrman grade were independent prognostic factors of outcome (p<001). Conclusions: The Motzer criteria were validated in patients with mRCC receiving TT. ECOG PS, nephrectomy, Fuhrman grade and number of sites of disease are independent prognostic factors of outcome.