Abstract
4615 Background: Efficacy and tolerability of chemo-immunotherapy plus anti-VEGF therapy is unknown. Aim of this study is to explore the combination of B+IT+C and to correlate its efficacy with the variations in circulating TREG. Methods: Patients (pts) with clear cell mRCC, previous nephrectomy, PS 0-1, no untreated CNS metastases and 0-2 previous systemic regimens, were treated with B (10 mg/kg days 1 and 15) plus C (gemcitabine: 1,000 mg/m2 i.v. in 1 hour followed by 5-fluorouracil 600 mg/m2 iv bolus days 1 and 8 every 28) plus IT (IL-2: 1 MUI/m2 bid sc days 8, 9, 15, 16 and 1 MUI/m2/die sc from day 10 to 12 and from 17 to 19; and IFN-α: 3 MUI sc on days 10, 12, 17, 19). The study was conducted according to two stages Minimax Simon design. CT was repeated for a maximum of 6 cycles followed by maintenance with B and IT until progressive disease (PD). In 30 pts, blood samples for TREG were collected and evaluated by FACS analysis. TREG were identified as CD4+/CD25high/FoxP3+ in PBMCs, on days: 1, 8, 15, 22, 29 of cycle 1 and at the disease progression (PD). Recist criteria and ITT analysis were applied. Results: 51 pts were included: male 66%; median age 58 ys; pre-treated 49%; MSKCC risk: low 29%, intermediate 53%, high 18%. We observed 29% partial response (PR) and 37% stable disease (SD) for an overall disease control rate (DCR) of 66%. In 26 not pre-treated pts 38% RP and 42% SD for a DCR of 80%. Median TTP was 8.8 mo and median OS 22,7 mo. In MSKCC high risk group we observed 11% PR and a DCR of 55%. Treatment was well tolerated, grade 3-4 toxicity included neutropenia non-febrile 36%, febrile 2%, thrombocytopenia 27%, flu-like syndrome 19%, hypertension 7%. We observed an increased percentage of TREG cells after treatment with IL2 + IFN and a decrease after treatment with B. The decrease was more evident in pts with PR or SD, suggesting a predictive role of TREG in the response to B. Conclusions: BIC combination is effective in all subgroups of mRCC and well tolerated. Variation in circulating TREG during first cycle seems to correlate with the response to treatment. Author Disclosure Employment or Leadership Position Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Roche
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