Antitumor activity of nivolumab in recurrent and metastatic nasopharyngeal carcinoma

An international, multicenter study of the mayo clinic phase 2 consortium (NCI-9742)

Brigette B.Y. Ma, Wan Teck Lim, Boon Cher Goh, Edwin P. Hui, Kwok Wai Lo, Adam Pettinger, Nathan R. Foster, Jonathan W. Riess, Mark Agulnik, Alex Y.C. Chang, Akhil Chopra, Julie A. Kish, Christine H. Chung, Douglas R. Adkins, Kevin J. Cullen, Barbara J. Gitlitz, Dean W. Lim, Ka Fai To, K. C.Allen Chan, Y. M.Dennis Lo & 5 others Ann D. King, Charles Erlichman, Jun Yin, Brian Costello, Anthony T.C. Chan

Research output: Contribution to journalArticle

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Abstract

Purpose This multinational study evaluated the antitumor activity of nivolumab in nasopharyngeal carcinoma (NPC). Tumor and plasma-based biomarkers were investigated in an exploratory analysis. Patients and Methods Patients with multiply pretreated recurrent or metastatic NPC were treated with nivolumab until disease progression. The primary end point was objective response rate (ORR) and secondary end points included survival and toxicity. The expression of programmed death-ligand 1 (PD-L1) and human leukocyte antigens A and B in archived tumors and plasma clearance of Epstein-Barr virus DNA were correlated with ORR and survival. Results A total of 44 patients were evaluated and the overall ORR was 20.5% (complete response, n = 1; partial response, n = 8). Nine patients received nivolumab for . 12 months (20%). The 1-year overall survival rate was 59% (95% CI, 44.3% to 78.5%) and 1-year progression-free survival (PFS) rate was 19.3% (95% CI, 10.1% to 37.2%). There was no statistical correlation between ORR and the biomarkers; however, a descriptive analysis showed that the proportion of patients who responded was higher among those with PD-L1 positive tumors (. 1% expression) than those with PD-L1-negative tumors. The loss of expression of one or both human leukocyte antigen class 1 proteins was associated with better PFS than when both proteins were expressed (1-year PFS, 30.9% v 5.6%; log-rank P = .01). There was no association between survival and PD-L1 expression or plasma Epstein-Barr virus DNA clearance. There was no unexpected toxicity to nivolumab. Conclusion Nivolumab has promising activity in NPC and the 1-year overall survival rate compares favorably with historic data in similar populations. Additional evaluation in a randomized setting is warranted. The biomarker results were hypothesis generating and validation in larger cohorts is needed.

Original languageEnglish (US)
Pages (from-to)1412-1418
Number of pages7
JournalJournal of Clinical Oncology
Volume36
Issue number14
DOIs
StatePublished - Jan 1 2018

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Multicenter Studies
Survival Rate
Ligands
Disease-Free Survival
Biomarkers
HLA Antigens
Human Herpesvirus 4
Neoplasms
Survival
DNA
Disease Progression
Proteins
Nasopharyngeal carcinoma
nivolumab
Population

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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Antitumor activity of nivolumab in recurrent and metastatic nasopharyngeal carcinoma : An international, multicenter study of the mayo clinic phase 2 consortium (NCI-9742). / Ma, Brigette B.Y.; Lim, Wan Teck; Goh, Boon Cher; Hui, Edwin P.; Lo, Kwok Wai; Pettinger, Adam; Foster, Nathan R.; Riess, Jonathan W.; Agulnik, Mark; Chang, Alex Y.C.; Chopra, Akhil; Kish, Julie A.; Chung, Christine H.; Adkins, Douglas R.; Cullen, Kevin J.; Gitlitz, Barbara J.; Lim, Dean W.; To, Ka Fai; Chan, K. C.Allen; Lo, Y. M.Dennis; King, Ann D.; Erlichman, Charles; Yin, Jun; Costello, Brian; Chan, Anthony T.C.

In: Journal of Clinical Oncology, Vol. 36, No. 14, 01.01.2018, p. 1412-1418.

Research output: Contribution to journalArticle

Ma, BBY, Lim, WT, Goh, BC, Hui, EP, Lo, KW, Pettinger, A, Foster, NR, Riess, JW, Agulnik, M, Chang, AYC, Chopra, A, Kish, JA, Chung, CH, Adkins, DR, Cullen, KJ, Gitlitz, BJ, Lim, DW, To, KF, Chan, KCA, Lo, YMD, King, AD, Erlichman, C, Yin, J, Costello, B & Chan, ATC 2018, 'Antitumor activity of nivolumab in recurrent and metastatic nasopharyngeal carcinoma: An international, multicenter study of the mayo clinic phase 2 consortium (NCI-9742)', Journal of Clinical Oncology, vol. 36, no. 14, pp. 1412-1418. https://doi.org/10.1200/JCO.2017.77.0388
Ma, Brigette B.Y. ; Lim, Wan Teck ; Goh, Boon Cher ; Hui, Edwin P. ; Lo, Kwok Wai ; Pettinger, Adam ; Foster, Nathan R. ; Riess, Jonathan W. ; Agulnik, Mark ; Chang, Alex Y.C. ; Chopra, Akhil ; Kish, Julie A. ; Chung, Christine H. ; Adkins, Douglas R. ; Cullen, Kevin J. ; Gitlitz, Barbara J. ; Lim, Dean W. ; To, Ka Fai ; Chan, K. C.Allen ; Lo, Y. M.Dennis ; King, Ann D. ; Erlichman, Charles ; Yin, Jun ; Costello, Brian ; Chan, Anthony T.C. / Antitumor activity of nivolumab in recurrent and metastatic nasopharyngeal carcinoma : An international, multicenter study of the mayo clinic phase 2 consortium (NCI-9742). In: Journal of Clinical Oncology. 2018 ; Vol. 36, No. 14. pp. 1412-1418.
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title = "Antitumor activity of nivolumab in recurrent and metastatic nasopharyngeal carcinoma: An international, multicenter study of the mayo clinic phase 2 consortium (NCI-9742)",
abstract = "Purpose This multinational study evaluated the antitumor activity of nivolumab in nasopharyngeal carcinoma (NPC). Tumor and plasma-based biomarkers were investigated in an exploratory analysis. Patients and Methods Patients with multiply pretreated recurrent or metastatic NPC were treated with nivolumab until disease progression. The primary end point was objective response rate (ORR) and secondary end points included survival and toxicity. The expression of programmed death-ligand 1 (PD-L1) and human leukocyte antigens A and B in archived tumors and plasma clearance of Epstein-Barr virus DNA were correlated with ORR and survival. Results A total of 44 patients were evaluated and the overall ORR was 20.5{\%} (complete response, n = 1; partial response, n = 8). Nine patients received nivolumab for . 12 months (20{\%}). The 1-year overall survival rate was 59{\%} (95{\%} CI, 44.3{\%} to 78.5{\%}) and 1-year progression-free survival (PFS) rate was 19.3{\%} (95{\%} CI, 10.1{\%} to 37.2{\%}). There was no statistical correlation between ORR and the biomarkers; however, a descriptive analysis showed that the proportion of patients who responded was higher among those with PD-L1 positive tumors (. 1{\%} expression) than those with PD-L1-negative tumors. The loss of expression of one or both human leukocyte antigen class 1 proteins was associated with better PFS than when both proteins were expressed (1-year PFS, 30.9{\%} v 5.6{\%}; log-rank P = .01). There was no association between survival and PD-L1 expression or plasma Epstein-Barr virus DNA clearance. There was no unexpected toxicity to nivolumab. Conclusion Nivolumab has promising activity in NPC and the 1-year overall survival rate compares favorably with historic data in similar populations. Additional evaluation in a randomized setting is warranted. The biomarker results were hypothesis generating and validation in larger cohorts is needed.",
author = "Ma, {Brigette B.Y.} and Lim, {Wan Teck} and Goh, {Boon Cher} and Hui, {Edwin P.} and Lo, {Kwok Wai} and Adam Pettinger and Foster, {Nathan R.} and Riess, {Jonathan W.} and Mark Agulnik and Chang, {Alex Y.C.} and Akhil Chopra and Kish, {Julie A.} and Chung, {Christine H.} and Adkins, {Douglas R.} and Cullen, {Kevin J.} and Gitlitz, {Barbara J.} and Lim, {Dean W.} and To, {Ka Fai} and Chan, {K. C.Allen} and Lo, {Y. M.Dennis} and King, {Ann D.} and Charles Erlichman and Jun Yin and Brian Costello and Chan, {Anthony T.C.}",
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TY - JOUR

T1 - Antitumor activity of nivolumab in recurrent and metastatic nasopharyngeal carcinoma

T2 - An international, multicenter study of the mayo clinic phase 2 consortium (NCI-9742)

AU - Ma, Brigette B.Y.

AU - Lim, Wan Teck

AU - Goh, Boon Cher

AU - Hui, Edwin P.

AU - Lo, Kwok Wai

AU - Pettinger, Adam

AU - Foster, Nathan R.

AU - Riess, Jonathan W.

AU - Agulnik, Mark

AU - Chang, Alex Y.C.

AU - Chopra, Akhil

AU - Kish, Julie A.

AU - Chung, Christine H.

AU - Adkins, Douglas R.

AU - Cullen, Kevin J.

AU - Gitlitz, Barbara J.

AU - Lim, Dean W.

AU - To, Ka Fai

AU - Chan, K. C.Allen

AU - Lo, Y. M.Dennis

AU - King, Ann D.

AU - Erlichman, Charles

AU - Yin, Jun

AU - Costello, Brian

AU - Chan, Anthony T.C.

PY - 2018/1/1

Y1 - 2018/1/1

N2 - Purpose This multinational study evaluated the antitumor activity of nivolumab in nasopharyngeal carcinoma (NPC). Tumor and plasma-based biomarkers were investigated in an exploratory analysis. Patients and Methods Patients with multiply pretreated recurrent or metastatic NPC were treated with nivolumab until disease progression. The primary end point was objective response rate (ORR) and secondary end points included survival and toxicity. The expression of programmed death-ligand 1 (PD-L1) and human leukocyte antigens A and B in archived tumors and plasma clearance of Epstein-Barr virus DNA were correlated with ORR and survival. Results A total of 44 patients were evaluated and the overall ORR was 20.5% (complete response, n = 1; partial response, n = 8). Nine patients received nivolumab for . 12 months (20%). The 1-year overall survival rate was 59% (95% CI, 44.3% to 78.5%) and 1-year progression-free survival (PFS) rate was 19.3% (95% CI, 10.1% to 37.2%). There was no statistical correlation between ORR and the biomarkers; however, a descriptive analysis showed that the proportion of patients who responded was higher among those with PD-L1 positive tumors (. 1% expression) than those with PD-L1-negative tumors. The loss of expression of one or both human leukocyte antigen class 1 proteins was associated with better PFS than when both proteins were expressed (1-year PFS, 30.9% v 5.6%; log-rank P = .01). There was no association between survival and PD-L1 expression or plasma Epstein-Barr virus DNA clearance. There was no unexpected toxicity to nivolumab. Conclusion Nivolumab has promising activity in NPC and the 1-year overall survival rate compares favorably with historic data in similar populations. Additional evaluation in a randomized setting is warranted. The biomarker results were hypothesis generating and validation in larger cohorts is needed.

AB - Purpose This multinational study evaluated the antitumor activity of nivolumab in nasopharyngeal carcinoma (NPC). Tumor and plasma-based biomarkers were investigated in an exploratory analysis. Patients and Methods Patients with multiply pretreated recurrent or metastatic NPC were treated with nivolumab until disease progression. The primary end point was objective response rate (ORR) and secondary end points included survival and toxicity. The expression of programmed death-ligand 1 (PD-L1) and human leukocyte antigens A and B in archived tumors and plasma clearance of Epstein-Barr virus DNA were correlated with ORR and survival. Results A total of 44 patients were evaluated and the overall ORR was 20.5% (complete response, n = 1; partial response, n = 8). Nine patients received nivolumab for . 12 months (20%). The 1-year overall survival rate was 59% (95% CI, 44.3% to 78.5%) and 1-year progression-free survival (PFS) rate was 19.3% (95% CI, 10.1% to 37.2%). There was no statistical correlation between ORR and the biomarkers; however, a descriptive analysis showed that the proportion of patients who responded was higher among those with PD-L1 positive tumors (. 1% expression) than those with PD-L1-negative tumors. The loss of expression of one or both human leukocyte antigen class 1 proteins was associated with better PFS than when both proteins were expressed (1-year PFS, 30.9% v 5.6%; log-rank P = .01). There was no association between survival and PD-L1 expression or plasma Epstein-Barr virus DNA clearance. There was no unexpected toxicity to nivolumab. Conclusion Nivolumab has promising activity in NPC and the 1-year overall survival rate compares favorably with historic data in similar populations. Additional evaluation in a randomized setting is warranted. The biomarker results were hypothesis generating and validation in larger cohorts is needed.

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U2 - 10.1200/JCO.2017.77.0388

DO - 10.1200/JCO.2017.77.0388

M3 - Article

VL - 36

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EP - 1418

JO - Journal of Clinical Oncology

JF - Journal of Clinical Oncology

SN - 0732-183X

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