期刊
CLINICAL CANCER RESEARCH
卷 23, 期 6, 页码 1388-1396出版社
AMER ASSOC CANCER RESEARCH
DOI: 10.1158/1078-0432.CCR-16-1432
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- National Cancer Institute Cancer Center Support (Core) Grant [NCI CA016672]
Purpose: Little prospective data are available on clinical outcomes and immune correlates from combination radiation and immunotherapy. We conducted a phase I trial (NCT02239900) testing stereotactic ablative radiotherapy (SABR) with ipilimumab. Experimental Design: SABR was given either concurrently (1 day after the first dose) or sequentially (1 week after the second dose) with ipilimumab (3 mg/kg every 3 weeks for 4 doses) to five treatment groups: concurrent 50 Gy (in 4 fractions) to liver; sequential 50 Gy (in 4 fractions) to liver; concurrent 50 Gy (in 4 fractions) to lung; sequential 50 Gy (in 4 fractions) to lung; and sequential 60 Gy (in 10 fractions) to lung or liver. MTD was determined with a 3 + 3 dose deescalation design. Immune marker expression was assessed by flow cytometry. Results: Among 35 patients who initiated ipilimumab, 2 experienced dose-limiting toxicity and 12 (34%) grade 3 toxicity. Response outside the radiation field was assessable in 31 patients. Three patients (10%) exhibited partial response and 7 (23%) experienced clinical benefit (defined as partial response or stable disease lasting >= 6 months). Clinical benefit was associated with increases in peripheral CD8(+) T cells, CD8(+)/CD4(+) T-cell ratio, and proportion of CD8(+) T cells expressing 4-1BB and PD1. Liver (vs. lung) irradiation produced greater T-cell activation, reflected as increases in the proportions of peripheral T cells expressing ICOS, GITR, and 4-1BB. Conclusions: Combining SABR and ipilimumab was safe with signs of efficacy, peripheral T-cell markers may predict clinical benefit, and systemic immune activation was greater after liver irradiation. (C) 2016 AACR.
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