鼻咽癌
医学
肿瘤科
封锁
内科学
CTLA-4号机组
免疫系统
生物标志物
癌症研究
免疫学
T细胞
受体
放射治疗
生物
生物化学
作者
Wan‐Teck Lim,Hsiang‐Fong Kao,Lisda Suteja,Constance H. Li,Hong Sheng Quah,Daniel S.W. Tan,Sze Huey Tan,Eng-Huat Tan,Wan-Ling Tan,Justina Nadia Lee,Felicia Yu-Ting Wee,Amit Jain,Boon Cher Goh,Melvin L.K. Chua,Bin-Chi Liao,Quan Sing Ng,Ruey‐Long Hong,Mei‐Kim Ang,Joe Yeong,N. Gopalakrishna Iyer
标识
DOI:10.1038/s41467-023-38407-7
摘要
Single-agent checkpoint inhibitor (CPI) activity in Epstein-Barr Virus (EBV) related nasopharyngeal carcinoma (NPC) is limited. Dual CPI shows increased activity in solid cancers. In this single-arm phase II trial (NCT03097939), 40 patients with recurrent/metastatic EBV-positive NPC who failed prior chemotherapy receive nivolumab 3 mg/kg every 2 weeks and ipilimumab 1 mg/kg every 6 weeks. Primary outcome of best overall response rate (BOR) and secondary outcomes (progression-free survival [PFS], clinical benefit rate, adverse events, duration of response, time to progression, overall survival [OS]) are reported. The BOR is 38% with median PFS and OS of 5.3 and 19.5 months, respectively. This regimen is well-tolerated and treatment-related adverse events requiring discontinuation are low. Biomarker analysis shows no correlation of outcomes to PD-L1 expression or tumor mutation burden. While the BOR does not meet pre-planned estimates, patients with low plasma EBV-DNA titre (<7800 IU/ml) trend to better response and PFS. Deep immunophenotyping of pre- and on-treatment tumor biopsies demonstrate early activation of the adaptive immune response, with T-cell cytotoxicity seen in responders prior to any clinically evident response. Immune-subpopulation profiling also identifies specific PD-1 and CTLA-4 expressing CD8 subpopulations that predict for response to combined immune checkpoint blockade in NPC.
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