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- Title
Clinical efficacy and biomarker analysis of dual PD-1/CTLA-4 blockade in recurrent/metastatic EBV-associated nasopharyngeal carcinoma.
- Authors
Lim, Darren Wan-Teck; Kao, Hsiang-Fong; 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.; Liao, Bin-Chi; Ng, Quan Sing; Hong, Ruey-Long; Ang, Mei-Kim; Yeong, Joe Poh-Sheng; Iyer, N. Gopalakrishna
- Abstract
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. Dual PD-1 and CTLA-4 checkpoint blockade has proven effective in several cancer types. Here the authors report the results of a clinical trial of anti-PD1 (nivolumab) and anti-CTLA4 (ipilimumab) in patients with recurrent/metastatic EBV-positive nasopharyngeal carcinoma.
- Subjects
NASOPHARYNX cancer; IMMUNE checkpoint proteins; PROGRAMMED cell death 1 receptors; BIOMARKERS; ADVERSE health care events; ALPHA fetoproteins; METASTASIS; CETUXIMAB
- Publication
Nature Communications, 2023, Vol 14, Issue 1, p1
- ISSN
2041-1723
- Publication type
Article
- DOI
10.1038/s41467-023-38407-7