A randomized phase II trial of interleukin-2 and interferon- plus bevacizumab versus interleukin-2 and interferon- in metastatic renal-cell carcinoma (mRCC): results from the Danish Renal Cancer Group (DaRenCa) study-1

作者：Donskov Frede^*; Jensen Niels Viggo; Smidt Hansen Torben; Brondum Line; Geertsen Poul

来源：Acta Oncologica, 2018, 57(5): 589-594.

DOI：10.1080/0284186X.2018.1433324

Background: Interleukin-2 (IL2)-based immunotherapy is curative for a small subset of patients with metastatic renal-cell carcinoma (mRCC). Preclinical data suggests that bevacizumab (BEV), a humanized anti-VEGF monoclonal antibody, has potential immunomodulatory effects by permitting efficient natural killer (NK) cell-mediated killing and by reverting immune suppression.Patient and methods: We performed a randomized phase II study comparing IL2/IFN (interferon)/BEV with IL2/IFN in favourable/intermediate-risk mRCC patients. One hundred and eighteen patients received IFN 3MIU subcutaneously (sc) daily and IL2 2.4MIU/m(2) sc twice daily, 5days per week for two consecutive weeks every 28-day-cycle, for 9months; or supplemented with BEV 10mg/kg, every 2weeks intravenously (iv) until progression, unacceptable toxicity, or 1year following no evidence of disease (NED). Primary end point was progression-free survival (PFS).Results: Baseline characteristics were well-balanced between the two arms; metastasis-free interval <1year (75 versus 76%); prior nephrectomy (85 versus 86%); MSKCC favourable/intermediate-risk group (51/49 versus 52%/48%); three or more disease sites (41 versus 44%), respectively. The median PFS was 8.0mo (95% CI, 4.2-11.9) with IL2/IFN/BEV and 8.1mo (95% CI, 5.1-11.0) with IL2/IFN, p=.73. There was no difference in secondary endpoints, IL2/IFN/BEV versus IL2/IFN; median time-to-treatment failure (7.4 versus 5.6mo, p=.54), response rate (44.1 versus 28.8%, p=.13), surgery of residual disease (17.0 versus 17.0%, p=1.0), patients achieving NED (3.4 versus 8.5%, p=.44), and median overall survival (30.3 versus 34.1mo, p=.39), respectively. TKI post progression was well-balanced (85 versus 78%). No new/unexpected toxicity was observed. Most common Grade 3/4 adverse events for IL2/IFN/BEV and IL2/IFN were fatigue (64 versus 61%), flu-like symptoms (37 versus 41%) and thrombosis (6.8 versus 18.6%, p=.01), respectively.Conclusions: The addition of BEV to IL-2/IFN did not add efficacy in mRCC. (ClinicalTrials.gov, NCT01274273.).

• 出版日期2018