PURPOSEThe regimens approved for the treatment of advanced head and neck squamous cell carcinoma are accessible to only 1%-3% of patients in low- and middle-income countries because of their cost. In our previous study, metronomic chemotherapy improved survival in this setting. Retrospective data suggest that a low dose of nivolumab may be efficacious. Hence, we aimed to assess whether the addition of low-dose nivolumab to triple metronomic chemotherapy (TMC) improved overall survival (OS).METHODSThis was a randomized phase III superiority study. Adult patients with recurrent or newly diagnosed advanced head and neck squamous cell carcinoma being treated with palliative intent with an Eastern Cooperative Oncology Group performance status of 0-1 were eligible. Patients were randomly assigned 1:1 to TMC consisting of oral methotrexate 9 mg/m(2) once a week, celecoxib 200 mg twice daily, and erlotinib 150 mg once daily, or TMC with intravenous nivolumab (TMC-I) 20 mg flat dose once every 3 weeks. The primary end point was 1-year OS.RESULTSOne hundred fifty-one patients were randomly assigned, 75 in TMC and 76 in the TMC-I arm. The addition of low-dose nivolumab led to an improvement in the 1-year OS from 16.3% (95% CI, 8.0 to 27.4) to 43.4% (95% CI, 30.8 to 55.3; hazard ratio, 0.545; 95% CI, 0.362 to 0.820; P = .0036). The median OS in TMC and TMC-I arms was 6.7 months (95% CI, 5.8 to 8.1) and 10.1 months (95% CI, 7.4 to 12.6), respectively (P = .0052). The rate of grade 3 and above adverse events was 50% and 46.1% in TMC and TMC-I arms, respectively (P = .744).CONCLUSIONTo our knowledge, this is the first-ever randomized study to demonstrate that the addition of low-dose nivolumab to metronomic chemotherapy improved OS and is an alternative standard of care for those who cannot access full-dose checkpoint inhibitors.
机构:
Shaare Zedek Med Ctr, Dept Med Oncol, Canc Pain & Palliat Med Serv, Jerusalem, IsraelShaare Zedek Med Ctr, Dept Med Oncol, Canc Pain & Palliat Med Serv, Jerusalem, Israel
Cherny, N. I.
Dafni, U.
论文数: 0引用数: 0
h-index: 0
机构:
Natl & Kapodistrian Univ Athens, Sch Hlth Sci, Lab Biostat, Athens, Greece
Frontier Sci Fdn Hellas, Athens, GreeceShaare Zedek Med Ctr, Dept Med Oncol, Canc Pain & Palliat Med Serv, Jerusalem, Israel
Dafni, U.
Bogaerts, J.
论文数: 0引用数: 0
h-index: 0
机构:
EORTC Headquarters, Methodol Direct, Brussels, BelgiumShaare Zedek Med Ctr, Dept Med Oncol, Canc Pain & Palliat Med Serv, Jerusalem, Israel
Bogaerts, J.
Latino, N. J.
论文数: 0引用数: 0
h-index: 0
机构:
ESMO Head Off, Lugano, SwitzerlandShaare Zedek Med Ctr, Dept Med Oncol, Canc Pain & Palliat Med Serv, Jerusalem, Israel
Latino, N. J.
Pentheroudakis, G.
论文数: 0引用数: 0
h-index: 0
机构:
Ioannina Univ Hosp, Med Oncol Dept, Ioannina, GreeceShaare Zedek Med Ctr, Dept Med Oncol, Canc Pain & Palliat Med Serv, Jerusalem, Israel
Pentheroudakis, G.
Douillard, J. -Y.
论文数: 0引用数: 0
h-index: 0
机构:
ESMO Head Off, Lugano, SwitzerlandShaare Zedek Med Ctr, Dept Med Oncol, Canc Pain & Palliat Med Serv, Jerusalem, Israel
Douillard, J. -Y.
Tabernero, J.
论文数: 0引用数: 0
h-index: 0
机构:
Vall Hebron Univ Hosp, Med Oncol Dept, Barcelona, SpainShaare Zedek Med Ctr, Dept Med Oncol, Canc Pain & Palliat Med Serv, Jerusalem, Israel
Tabernero, J.
Zielinski, C.
论文数: 0引用数: 0
h-index: 0
机构:
Med Univ Vienna, Div Oncol, Vienna, AustriaShaare Zedek Med Ctr, Dept Med Oncol, Canc Pain & Palliat Med Serv, Jerusalem, Israel
Zielinski, C.
Piccart, M. J.
论文数: 0引用数: 0
h-index: 0
机构:
Univ Libre Bruxelles, Jules Bordet Inst, Brussels, BelgiumShaare Zedek Med Ctr, Dept Med Oncol, Canc Pain & Palliat Med Serv, Jerusalem, Israel
Piccart, M. J.
de Vries, E. G. E.
论文数: 0引用数: 0
h-index: 0
机构:
Univ Groningen, Univ Med Ctr Groningen, Dept Med Oncol, Groningen, NetherlandsShaare Zedek Med Ctr, Dept Med Oncol, Canc Pain & Palliat Med Serv, Jerusalem, Israel
机构:
Univ Calif San Diego, San Diego Moores Canc Ctr, San Diego, CA 92093 USAUniv Calif San Diego, San Diego Moores Canc Ctr, San Diego, CA 92093 USA
Cohen, Ezra E. W.
Soulieres, Denis
论文数: 0引用数: 0
h-index: 0
机构:
Ctr Hosp Univ Montreal, Montreal, PQ, CanadaUniv Calif San Diego, San Diego Moores Canc Ctr, San Diego, CA 92093 USA
Soulieres, Denis
Le Tourneau, Christophe
论文数: 0引用数: 0
h-index: 0
机构:
Inst Curie, Dept Drug Dev & Innovat, Paris, France
INSERM, Res Unit U900, Paris, France
Versailles St Quentinen En Yvelines Univ, Paris, FranceUniv Calif San Diego, San Diego Moores Canc Ctr, San Diego, CA 92093 USA
Le Tourneau, Christophe
Dinis, Jose
论文数: 0引用数: 0
h-index: 0
机构:
Inst Portugues Oncol Porto Francisco Gentil, Porto, PortugalUniv Calif San Diego, San Diego Moores Canc Ctr, San Diego, CA 92093 USA
Dinis, Jose
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机构:
Licitra, Lisa
Ahn, Myung-Ju
论文数: 0引用数: 0
h-index: 0
机构:
Samsung Med Ctr, Seoul, South KoreaUniv Calif San Diego, San Diego Moores Canc Ctr, San Diego, CA 92093 USA
Ahn, Myung-Ju
Soria, Ainara
论文数: 0引用数: 0
h-index: 0
机构:
Hosp Univ Ramon & Cajal, Madrid, SpainUniv Calif San Diego, San Diego Moores Canc Ctr, San Diego, CA 92093 USA
Soria, Ainara
Machiels, Jean-Pascal
论文数: 0引用数: 0
h-index: 0
机构:
Clin Univ St Luc, Brussels, Belgium
Catholic Univ Louvain, Louvain La Neuve, BelgiumUniv Calif San Diego, San Diego Moores Canc Ctr, San Diego, CA 92093 USA
Machiels, Jean-Pascal
Mach, Nicolas
论文数: 0引用数: 0
h-index: 0
机构:
Hop Univ Geneve, Geneva, SwitzerlandUniv Calif San Diego, San Diego Moores Canc Ctr, San Diego, CA 92093 USA
Mach, Nicolas
Mehra, Ranee
论文数: 0引用数: 0
h-index: 0
机构:
Fox Chase Canc Ctr, 7701 Burholme Ave, Philadelphia, PA 19111 USA
Johns Hopkins Sidney Kimmel Comprehens Canc Ctr, Baltimore, MD USAUniv Calif San Diego, San Diego Moores Canc Ctr, San Diego, CA 92093 USA
Mehra, Ranee
Burtness, Barbara
论文数: 0引用数: 0
h-index: 0
机构:
Yale Univ, Sch Med, New Haven, CT USA
Yale Canc Ctr, New Haven, CT USAUniv Calif San Diego, San Diego Moores Canc Ctr, San Diego, CA 92093 USA
Burtness, Barbara
Zhang, Pingye
论文数: 0引用数: 0
h-index: 0
机构:
Merck & Co Inc, Kenilworth, NJ USAUniv Calif San Diego, San Diego Moores Canc Ctr, San Diego, CA 92093 USA
Zhang, Pingye
Cheng, Jonathan
论文数: 0引用数: 0
h-index: 0
机构:
Merck & Co Inc, Kenilworth, NJ USAUniv Calif San Diego, San Diego Moores Canc Ctr, San Diego, CA 92093 USA
Cheng, Jonathan
Swaby, Ramona F.
论文数: 0引用数: 0
h-index: 0
机构:
Merck & Co Inc, Kenilworth, NJ USAUniv Calif San Diego, San Diego Moores Canc Ctr, San Diego, CA 92093 USA
Swaby, Ramona F.
Harrington, Kevin J.
论文数: 0引用数: 0
h-index: 0
机构:
Inst Canc Res, London, England
Royal Marsden NHS Fdn Trust, Natl Inst Hlth Res, Biomed Res Ctr, London, EnglandUniv Calif San Diego, San Diego Moores Canc Ctr, San Diego, CA 92093 USA
机构:
Shaare Zedek Med Ctr, Dept Med Oncol, Canc Pain & Palliat Med Serv, Jerusalem, IsraelShaare Zedek Med Ctr, Dept Med Oncol, Canc Pain & Palliat Med Serv, Jerusalem, Israel
Cherny, N. I.
Dafni, U.
论文数: 0引用数: 0
h-index: 0
机构:
Natl & Kapodistrian Univ Athens, Sch Hlth Sci, Lab Biostat, Athens, Greece
Frontier Sci Fdn Hellas, Athens, GreeceShaare Zedek Med Ctr, Dept Med Oncol, Canc Pain & Palliat Med Serv, Jerusalem, Israel
Dafni, U.
Bogaerts, J.
论文数: 0引用数: 0
h-index: 0
机构:
EORTC Headquarters, Methodol Direct, Brussels, BelgiumShaare Zedek Med Ctr, Dept Med Oncol, Canc Pain & Palliat Med Serv, Jerusalem, Israel
Bogaerts, J.
Latino, N. J.
论文数: 0引用数: 0
h-index: 0
机构:
ESMO Head Off, Lugano, SwitzerlandShaare Zedek Med Ctr, Dept Med Oncol, Canc Pain & Palliat Med Serv, Jerusalem, Israel
Latino, N. J.
Pentheroudakis, G.
论文数: 0引用数: 0
h-index: 0
机构:
Ioannina Univ Hosp, Med Oncol Dept, Ioannina, GreeceShaare Zedek Med Ctr, Dept Med Oncol, Canc Pain & Palliat Med Serv, Jerusalem, Israel
Pentheroudakis, G.
Douillard, J. -Y.
论文数: 0引用数: 0
h-index: 0
机构:
ESMO Head Off, Lugano, SwitzerlandShaare Zedek Med Ctr, Dept Med Oncol, Canc Pain & Palliat Med Serv, Jerusalem, Israel
Douillard, J. -Y.
Tabernero, J.
论文数: 0引用数: 0
h-index: 0
机构:
Vall Hebron Univ Hosp, Med Oncol Dept, Barcelona, SpainShaare Zedek Med Ctr, Dept Med Oncol, Canc Pain & Palliat Med Serv, Jerusalem, Israel
Tabernero, J.
Zielinski, C.
论文数: 0引用数: 0
h-index: 0
机构:
Med Univ Vienna, Div Oncol, Vienna, AustriaShaare Zedek Med Ctr, Dept Med Oncol, Canc Pain & Palliat Med Serv, Jerusalem, Israel
Zielinski, C.
Piccart, M. J.
论文数: 0引用数: 0
h-index: 0
机构:
Univ Libre Bruxelles, Jules Bordet Inst, Brussels, BelgiumShaare Zedek Med Ctr, Dept Med Oncol, Canc Pain & Palliat Med Serv, Jerusalem, Israel
Piccart, M. J.
de Vries, E. G. E.
论文数: 0引用数: 0
h-index: 0
机构:
Univ Groningen, Univ Med Ctr Groningen, Dept Med Oncol, Groningen, NetherlandsShaare Zedek Med Ctr, Dept Med Oncol, Canc Pain & Palliat Med Serv, Jerusalem, Israel
机构:
Univ Calif San Diego, San Diego Moores Canc Ctr, San Diego, CA 92093 USAUniv Calif San Diego, San Diego Moores Canc Ctr, San Diego, CA 92093 USA
Cohen, Ezra E. W.
Soulieres, Denis
论文数: 0引用数: 0
h-index: 0
机构:
Ctr Hosp Univ Montreal, Montreal, PQ, CanadaUniv Calif San Diego, San Diego Moores Canc Ctr, San Diego, CA 92093 USA
Soulieres, Denis
Le Tourneau, Christophe
论文数: 0引用数: 0
h-index: 0
机构:
Inst Curie, Dept Drug Dev & Innovat, Paris, France
INSERM, Res Unit U900, Paris, France
Versailles St Quentinen En Yvelines Univ, Paris, FranceUniv Calif San Diego, San Diego Moores Canc Ctr, San Diego, CA 92093 USA
Le Tourneau, Christophe
Dinis, Jose
论文数: 0引用数: 0
h-index: 0
机构:
Inst Portugues Oncol Porto Francisco Gentil, Porto, PortugalUniv Calif San Diego, San Diego Moores Canc Ctr, San Diego, CA 92093 USA
Dinis, Jose
论文数: 引用数:
h-index:
机构:
Licitra, Lisa
Ahn, Myung-Ju
论文数: 0引用数: 0
h-index: 0
机构:
Samsung Med Ctr, Seoul, South KoreaUniv Calif San Diego, San Diego Moores Canc Ctr, San Diego, CA 92093 USA
Ahn, Myung-Ju
Soria, Ainara
论文数: 0引用数: 0
h-index: 0
机构:
Hosp Univ Ramon & Cajal, Madrid, SpainUniv Calif San Diego, San Diego Moores Canc Ctr, San Diego, CA 92093 USA
Soria, Ainara
Machiels, Jean-Pascal
论文数: 0引用数: 0
h-index: 0
机构:
Clin Univ St Luc, Brussels, Belgium
Catholic Univ Louvain, Louvain La Neuve, BelgiumUniv Calif San Diego, San Diego Moores Canc Ctr, San Diego, CA 92093 USA
Machiels, Jean-Pascal
Mach, Nicolas
论文数: 0引用数: 0
h-index: 0
机构:
Hop Univ Geneve, Geneva, SwitzerlandUniv Calif San Diego, San Diego Moores Canc Ctr, San Diego, CA 92093 USA
Mach, Nicolas
Mehra, Ranee
论文数: 0引用数: 0
h-index: 0
机构:
Fox Chase Canc Ctr, 7701 Burholme Ave, Philadelphia, PA 19111 USA
Johns Hopkins Sidney Kimmel Comprehens Canc Ctr, Baltimore, MD USAUniv Calif San Diego, San Diego Moores Canc Ctr, San Diego, CA 92093 USA
Mehra, Ranee
Burtness, Barbara
论文数: 0引用数: 0
h-index: 0
机构:
Yale Univ, Sch Med, New Haven, CT USA
Yale Canc Ctr, New Haven, CT USAUniv Calif San Diego, San Diego Moores Canc Ctr, San Diego, CA 92093 USA
Burtness, Barbara
Zhang, Pingye
论文数: 0引用数: 0
h-index: 0
机构:
Merck & Co Inc, Kenilworth, NJ USAUniv Calif San Diego, San Diego Moores Canc Ctr, San Diego, CA 92093 USA
Zhang, Pingye
Cheng, Jonathan
论文数: 0引用数: 0
h-index: 0
机构:
Merck & Co Inc, Kenilworth, NJ USAUniv Calif San Diego, San Diego Moores Canc Ctr, San Diego, CA 92093 USA
Cheng, Jonathan
Swaby, Ramona F.
论文数: 0引用数: 0
h-index: 0
机构:
Merck & Co Inc, Kenilworth, NJ USAUniv Calif San Diego, San Diego Moores Canc Ctr, San Diego, CA 92093 USA
Swaby, Ramona F.
Harrington, Kevin J.
论文数: 0引用数: 0
h-index: 0
机构:
Inst Canc Res, London, England
Royal Marsden NHS Fdn Trust, Natl Inst Hlth Res, Biomed Res Ctr, London, EnglandUniv Calif San Diego, San Diego Moores Canc Ctr, San Diego, CA 92093 USA