Gemcitabine, carboplatin, and Epstein–Barr virus-specific autologous cytotoxic T lymphocytes for recurrent or metastatic nasopharyngeal carcinoma: VANCE, an international randomized phase III trial
Issued Date
2024-01-01
Resource Type
ISSN
09237534
eISSN
15698041
Scopus ID
2-s2.0-85205601010
Pubmed ID
39241963
Journal Title
Annals of Oncology
Rights Holder(s)
SCOPUS
Bibliographic Citation
Annals of Oncology (2024)
Suggested Citation
Toh H.C., Yang M.H., Wang H.M., Hsieh C.Y., Chitapanarux I., Ho K.F., Hong R.L., Ang M.K., Colevas A.D., Sirachainan E., Lertbutsayanukul C., Ho G.F., Nadler E., Algazi A., Lulla P., Wirth L.J., Wirasorn K., Liu Y.C., Ang S.F., Low S.H.J., Tho L.M., Hasbullah H.H., Brenner M.K., Wang W.W., Ong W.S., Tan S.H., Horak I., Ding C., Myo A., Samol J. Gemcitabine, carboplatin, and Epstein–Barr virus-specific autologous cytotoxic T lymphocytes for recurrent or metastatic nasopharyngeal carcinoma: VANCE, an international randomized phase III trial. Annals of Oncology (2024). doi:10.1016/j.annonc.2024.08.2344 Retrieved from: https://repository.li.mahidol.ac.th/handle/20.500.14594/101577
Title
Gemcitabine, carboplatin, and Epstein–Barr virus-specific autologous cytotoxic T lymphocytes for recurrent or metastatic nasopharyngeal carcinoma: VANCE, an international randomized phase III trial
Author(s)
Toh H.C.
Yang M.H.
Wang H.M.
Hsieh C.Y.
Chitapanarux I.
Ho K.F.
Hong R.L.
Ang M.K.
Colevas A.D.
Sirachainan E.
Lertbutsayanukul C.
Ho G.F.
Nadler E.
Algazi A.
Lulla P.
Wirth L.J.
Wirasorn K.
Liu Y.C.
Ang S.F.
Low S.H.J.
Tho L.M.
Hasbullah H.H.
Brenner M.K.
Wang W.W.
Ong W.S.
Tan S.H.
Horak I.
Ding C.
Myo A.
Samol J.
Yang M.H.
Wang H.M.
Hsieh C.Y.
Chitapanarux I.
Ho K.F.
Hong R.L.
Ang M.K.
Colevas A.D.
Sirachainan E.
Lertbutsayanukul C.
Ho G.F.
Nadler E.
Algazi A.
Lulla P.
Wirth L.J.
Wirasorn K.
Liu Y.C.
Ang S.F.
Low S.H.J.
Tho L.M.
Hasbullah H.H.
Brenner M.K.
Wang W.W.
Ong W.S.
Tan S.H.
Horak I.
Ding C.
Myo A.
Samol J.
Author's Affiliation
Ramathibodi Hospital
Lee Kong Chian School of Medicine
National Taiwan University Hospital
Stanford University School of Medicine
China Medical University Hospital
Chang Gung Memorial Hospital
National Cancer Centre, Singapore
Massachusetts General Hospital
Universiti Malaya
Kuala Lumpur Hospital
University of California, San Francisco
King Chulalongkorn Memorial Hospital
Khon Kaen University
Penang Adventist Hospital
Taipei Veterans General Hospital
Pantai Holdings Sdn Bhd
Texas Children's Hospital
Baylor Charles A. Sammons Cancer Center
Veterans General Hospital-Taichung Taiwan
Johns Hopkins University
Tan Tock Seng Hospital
Chiang Mai University
Tessa Therapeutics Ltd.
Beacon Hospital
Mount Miriam Cancer Hospital
Lee Kong Chian School of Medicine
National Taiwan University Hospital
Stanford University School of Medicine
China Medical University Hospital
Chang Gung Memorial Hospital
National Cancer Centre, Singapore
Massachusetts General Hospital
Universiti Malaya
Kuala Lumpur Hospital
University of California, San Francisco
King Chulalongkorn Memorial Hospital
Khon Kaen University
Penang Adventist Hospital
Taipei Veterans General Hospital
Pantai Holdings Sdn Bhd
Texas Children's Hospital
Baylor Charles A. Sammons Cancer Center
Veterans General Hospital-Taichung Taiwan
Johns Hopkins University
Tan Tock Seng Hospital
Chiang Mai University
Tessa Therapeutics Ltd.
Beacon Hospital
Mount Miriam Cancer Hospital
Corresponding Author(s)
Other Contributor(s)
Abstract
Background: Epstein–Barr virus-specific cytotoxic T lymphocyte (EBV-CTL) is an autologous adoptive T-cell immunotherapy generated from the blood of individuals and manufactured without genetic modification. In a previous phase II trial of locally recurrent or metastatic nasopharyngeal carcinoma (R/M NPC) patients, first-line gemcitabine and carboplatin (GC) and EBV-CTL combination demonstrated objective antitumor EBV-CTL activity and a favorable safety profile. The present study explored whether this combined first-line chemo-immunotherapy strategy would produce superior clinical efficacy and better quality of life compared with conventional chemotherapy treatment. Patients and methods: This multicenter, randomized, phase III trial evaluated the efficacy and safety of GC followed by EBV-CTL versus GC alone as first-line treatment of R/M NPC patients. Thirty clinical sites in Singapore, Malaysia, Taiwan, Thailand, and the USA were included. Subjects were randomized to first-line GC (four cycles) and EBV-CTL (six cycles) or GC (six cycles) in a 1 : 1 ratio. The primary outcome was overall survival (OS) and secondary outcomes included progression-free survival, objective response rate, clinical benefit rate, quality of life, and safety. ClinicalTrials.gov identifier: NCT02578641. Results: A total of 330 subjects with NPC were enrolled. Most subjects in both treatment arms received four or more cycles of chemotherapy and most subjects in the GC + EBV-CTL group received two or more infusions of EBV-CTL. The central Good Manufacturing Practices (GMP) facility produced sufficient EBV-CTL for 94% of GC + EBV-CTL subjects. The median OS was 25.0 months in the GC + EBV-CTL group and 24.9 months in the GC group (hazard ratio = 1.19; 95% confidence interval 0.91-1.56; P = 0.194). Only one subject experienced a grade 2 serious adverse event related to EBV-CTL. Conclusions: GC + EBV-CTL in subjects with R/M NPC demonstrated a favorable safety profile but no overall improvement in OS versus chemotherapy. This is the largest adoptive T-cell therapy trial reported in solid tumors to date.