https://scholars.lib.ntu.edu.tw/handle/123456789/633596
標題: | Clinical efficacy and biomarker analysis of dual PD-1/CTLA-4 blockade in recurrent/metastatic EBV-associated nasopharyngeal carcinoma | 作者: | Lim, Darren Wan-Teck HSIANG-FONG KAO Suteja, Lisda Li, Constance H Quah, Hong Sheng Tan, Daniel Shao-Weng Tan, Sze-Huey Tan, Eng-Huat Tan, Wan-Ling Lee, Justina Nadia Wee, Felicia Yu-Ting Jain, Amit Goh, Boon-Cher Chua, Melvin L K BIN-CHI LIAO Ng, Quan Sing RUEY-LONG HONG Ang, Mei-Kim Yeong, Joe Poh-Sheng Iyer, N Gopalakrishna |
公開日期: | 15-五月-2023 | 卷: | 14 | 期: | 1 | 來源出版物: | Nature communications | 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. |
URI: | https://scholars.lib.ntu.edu.tw/handle/123456789/633596 | ISSN: | 2041-1723 | DOI: | 10.1038/s41467-023-38407-7 |
顯示於: | 腫瘤醫學研究所 |
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