期刊
BRITISH JOURNAL OF CANCER
卷 119, 期 10, 页码 1200-1207出版社
NATURE PUBLISHING GROUP
DOI: 10.1038/s41416-018-0281-9
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资金
- National Institutes of Health [P50 CA174523, P01-CA-210944, P30-CA-016520]
- Merck
- NATIONAL CANCER INSTITUTE [P01CA210944, P50CA174523, P30CA016520] Funding Source: NIH RePORTER
BACKGROUND: We conducted a phase I trial evaluating pembrolizumab+hypofractionated radiotherapy (HFRT) for patients with metastatic cancers. METHODS: There were two strata (12 patients each): (i) NSCLC/melanoma progressing on prior anti-PD-1 therapy, (ii) other cancer types; anti-PD-1-naive. Patients received 6 cycles of pembrolizumab, starting 1 week before HFRT. Patients had >= 2 lesions; only one was irradiated (8 Gy x 3 for first half; 17 Gy x 1 for second half in each stratum) and the other(s) followed for response. RESULTS: Of the 24 patients, 20 (83%) had treatment-related adverse events (AEs) (all grade 1 or 2). There were eight grade 3 AEs, none treatment related. There were no dose-limiting toxicities or grade 4/5 AEs. Stratum 1: two patients (of 12) with progression on prior PD-1 blockade experienced prolonged responses (9.2 and 28.1 months). Stratum 2: one patient experienced a complete response and two had prolonged stable disease (7.4 and 7.0 months). Immune profiling demonstrated that anti-PD-1 therapy and radiation induced a consistent increase in the proliferation marker Ki67 in PD-1-expressing CD8 T cells. CONCLUSIONS: HFRT was well tolerated with pembrolizumab, and in some patients with metastatic NSCLC or melanoma, it reinvigorated a systemic response despite previous progression on anti-PD-1 therapy.
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