Phase III Randomized Trial of Chemotherapy With or Without Bevacizumab in Patients With Recurrent or Metastatic Head and Neck Cancer

Athanassios Argiris, Shuli Li, Panayiotis Savvides, James P. Ohr, Jill Gilbert, Marshall A. Levine, Arnab Chakravarti, Missak Haigentz, Nabil F. Saba, Chukwuemeka V. Ikpeazu, Charles J. Schneider, Harlan A. Pinto, Arlene A. Forastiere, Barbara Burtness

Research output: Contribution to journalArticle

Abstract

PURPOSE: We evaluated the addition of bevacizumab, a humanized monoclonal antibody that targets vascular endothelial growth factor, to platinum-based chemotherapy in recurrent or metastatic squamous cell carcinoma of the head and neck (SCCHN). PATIENTS AND METHODS: Patients with chemotherapy-naïve (or with prior platinum as part of multimodal therapy completed ≥ 4 months earlier) recurrent or metastatic SCCHN were randomly assigned to receive a platinum-based chemotherapy doublet with or without bevacizumab 15 mg/kg given intravenously every 3 weeks until disease progression. Chemotherapy could be discontinued after six cycles if a maximum response was achieved. RESULTS: The study randomly assigned 403 patients. Median overall survival (OS) was 12.6 months with bevacizumab plus chemotherapy (BC) and 11.0 months with chemotherapy alone (hazard ratio, 0.87; 95% CI, 0.70 to 1.09; P = .22). At 2, 3, and 4 years, the OS rates were 25.2% v 18.1%, 16.4% v 10.0%, and 11.8% v 6.4% for BC versus chemotherapy, respectively. In an analysis of 365 eligible patients who started treatment, the hazard ratio was 0.82 (95% CI, 0.65 to 1.04; P = .10), with a median OS of 14.2 months on BC v 11.1 months on chemotherapy. Median progression-free survival with BC was 6.0 months v 4.3 months with chemotherapy (P = .0014). Overall response rates were 35.5% with BC and 24.5% with chemotherapy (P = .016). There was increased toxicity, including a higher rate of treatment-related grade 3 to 5 bleeding events (6.7% v 0.5%; P < .001) and treatment-related deaths (9.3% v 3.5%; P = .022) with BC versus chemotherapy. CONCLUSION: The addition of bevacizumab to chemotherapy did not improve OS but improved the response rate and progression-free survival with increased toxicities. These results encourage biomarker-driven studies of angiogenesis inhibitors with better toxicity profiles in select patients with SCCHN.

Original languageEnglish (US)
Pages (from-to)3266-3274
Number of pages9
JournalJournal of clinical oncology : official journal of the American Society of Clinical Oncology
Volume37
Issue number34
DOIs
StatePublished - Dec 1 2019

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Head and Neck Neoplasms
Drug Therapy
Platinum
Bevacizumab
Disease-Free Survival
Survival
Antibodies, Monoclonal, Humanized
Angiogenesis Inhibitors
Therapeutics
Vascular Endothelial Growth Factor A

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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Phase III Randomized Trial of Chemotherapy With or Without Bevacizumab in Patients With Recurrent or Metastatic Head and Neck Cancer. / Argiris, Athanassios; Li, Shuli; Savvides, Panayiotis; Ohr, James P.; Gilbert, Jill; Levine, Marshall A.; Chakravarti, Arnab; Haigentz, Missak; Saba, Nabil F.; Ikpeazu, Chukwuemeka V.; Schneider, Charles J.; Pinto, Harlan A.; Forastiere, Arlene A.; Burtness, Barbara.

In: Journal of clinical oncology : official journal of the American Society of Clinical Oncology, Vol. 37, No. 34, 01.12.2019, p. 3266-3274.

Research output: Contribution to journalArticle

Argiris, A, Li, S, Savvides, P, Ohr, JP, Gilbert, J, Levine, MA, Chakravarti, A, Haigentz, M, Saba, NF, Ikpeazu, CV, Schneider, CJ, Pinto, HA, Forastiere, AA & Burtness, B 2019, 'Phase III Randomized Trial of Chemotherapy With or Without Bevacizumab in Patients With Recurrent or Metastatic Head and Neck Cancer', Journal of clinical oncology : official journal of the American Society of Clinical Oncology, vol. 37, no. 34, pp. 3266-3274. https://doi.org/10.1200/JCO.19.00555
Argiris, Athanassios ; Li, Shuli ; Savvides, Panayiotis ; Ohr, James P. ; Gilbert, Jill ; Levine, Marshall A. ; Chakravarti, Arnab ; Haigentz, Missak ; Saba, Nabil F. ; Ikpeazu, Chukwuemeka V. ; Schneider, Charles J. ; Pinto, Harlan A. ; Forastiere, Arlene A. ; Burtness, Barbara. / Phase III Randomized Trial of Chemotherapy With or Without Bevacizumab in Patients With Recurrent or Metastatic Head and Neck Cancer. In: Journal of clinical oncology : official journal of the American Society of Clinical Oncology. 2019 ; Vol. 37, No. 34. pp. 3266-3274.
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abstract = "PURPOSE: We evaluated the addition of bevacizumab, a humanized monoclonal antibody that targets vascular endothelial growth factor, to platinum-based chemotherapy in recurrent or metastatic squamous cell carcinoma of the head and neck (SCCHN). PATIENTS AND METHODS: Patients with chemotherapy-na{\"i}ve (or with prior platinum as part of multimodal therapy completed ≥ 4 months earlier) recurrent or metastatic SCCHN were randomly assigned to receive a platinum-based chemotherapy doublet with or without bevacizumab 15 mg/kg given intravenously every 3 weeks until disease progression. Chemotherapy could be discontinued after six cycles if a maximum response was achieved. RESULTS: The study randomly assigned 403 patients. Median overall survival (OS) was 12.6 months with bevacizumab plus chemotherapy (BC) and 11.0 months with chemotherapy alone (hazard ratio, 0.87; 95{\%} CI, 0.70 to 1.09; P = .22). At 2, 3, and 4 years, the OS rates were 25.2{\%} v 18.1{\%}, 16.4{\%} v 10.0{\%}, and 11.8{\%} v 6.4{\%} for BC versus chemotherapy, respectively. In an analysis of 365 eligible patients who started treatment, the hazard ratio was 0.82 (95{\%} CI, 0.65 to 1.04; P = .10), with a median OS of 14.2 months on BC v 11.1 months on chemotherapy. Median progression-free survival with BC was 6.0 months v 4.3 months with chemotherapy (P = .0014). Overall response rates were 35.5{\%} with BC and 24.5{\%} with chemotherapy (P = .016). There was increased toxicity, including a higher rate of treatment-related grade 3 to 5 bleeding events (6.7{\%} v 0.5{\%}; P < .001) and treatment-related deaths (9.3{\%} v 3.5{\%}; P = .022) with BC versus chemotherapy. CONCLUSION: The addition of bevacizumab to chemotherapy did not improve OS but improved the response rate and progression-free survival with increased toxicities. These results encourage biomarker-driven studies of angiogenesis inhibitors with better toxicity profiles in select patients with SCCHN.",
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T1 - Phase III Randomized Trial of Chemotherapy With or Without Bevacizumab in Patients With Recurrent or Metastatic Head and Neck Cancer

AU - Argiris, Athanassios

AU - Li, Shuli

AU - Savvides, Panayiotis

AU - Ohr, James P.

AU - Gilbert, Jill

AU - Levine, Marshall A.

AU - Chakravarti, Arnab

AU - Haigentz, Missak

AU - Saba, Nabil F.

AU - Ikpeazu, Chukwuemeka V.

AU - Schneider, Charles J.

AU - Pinto, Harlan A.

AU - Forastiere, Arlene A.

AU - Burtness, Barbara

PY - 2019/12/1

Y1 - 2019/12/1

N2 - PURPOSE: We evaluated the addition of bevacizumab, a humanized monoclonal antibody that targets vascular endothelial growth factor, to platinum-based chemotherapy in recurrent or metastatic squamous cell carcinoma of the head and neck (SCCHN). PATIENTS AND METHODS: Patients with chemotherapy-naïve (or with prior platinum as part of multimodal therapy completed ≥ 4 months earlier) recurrent or metastatic SCCHN were randomly assigned to receive a platinum-based chemotherapy doublet with or without bevacizumab 15 mg/kg given intravenously every 3 weeks until disease progression. Chemotherapy could be discontinued after six cycles if a maximum response was achieved. RESULTS: The study randomly assigned 403 patients. Median overall survival (OS) was 12.6 months with bevacizumab plus chemotherapy (BC) and 11.0 months with chemotherapy alone (hazard ratio, 0.87; 95% CI, 0.70 to 1.09; P = .22). At 2, 3, and 4 years, the OS rates were 25.2% v 18.1%, 16.4% v 10.0%, and 11.8% v 6.4% for BC versus chemotherapy, respectively. In an analysis of 365 eligible patients who started treatment, the hazard ratio was 0.82 (95% CI, 0.65 to 1.04; P = .10), with a median OS of 14.2 months on BC v 11.1 months on chemotherapy. Median progression-free survival with BC was 6.0 months v 4.3 months with chemotherapy (P = .0014). Overall response rates were 35.5% with BC and 24.5% with chemotherapy (P = .016). There was increased toxicity, including a higher rate of treatment-related grade 3 to 5 bleeding events (6.7% v 0.5%; P < .001) and treatment-related deaths (9.3% v 3.5%; P = .022) with BC versus chemotherapy. CONCLUSION: The addition of bevacizumab to chemotherapy did not improve OS but improved the response rate and progression-free survival with increased toxicities. These results encourage biomarker-driven studies of angiogenesis inhibitors with better toxicity profiles in select patients with SCCHN.

AB - PURPOSE: We evaluated the addition of bevacizumab, a humanized monoclonal antibody that targets vascular endothelial growth factor, to platinum-based chemotherapy in recurrent or metastatic squamous cell carcinoma of the head and neck (SCCHN). PATIENTS AND METHODS: Patients with chemotherapy-naïve (or with prior platinum as part of multimodal therapy completed ≥ 4 months earlier) recurrent or metastatic SCCHN were randomly assigned to receive a platinum-based chemotherapy doublet with or without bevacizumab 15 mg/kg given intravenously every 3 weeks until disease progression. Chemotherapy could be discontinued after six cycles if a maximum response was achieved. RESULTS: The study randomly assigned 403 patients. Median overall survival (OS) was 12.6 months with bevacizumab plus chemotherapy (BC) and 11.0 months with chemotherapy alone (hazard ratio, 0.87; 95% CI, 0.70 to 1.09; P = .22). At 2, 3, and 4 years, the OS rates were 25.2% v 18.1%, 16.4% v 10.0%, and 11.8% v 6.4% for BC versus chemotherapy, respectively. In an analysis of 365 eligible patients who started treatment, the hazard ratio was 0.82 (95% CI, 0.65 to 1.04; P = .10), with a median OS of 14.2 months on BC v 11.1 months on chemotherapy. Median progression-free survival with BC was 6.0 months v 4.3 months with chemotherapy (P = .0014). Overall response rates were 35.5% with BC and 24.5% with chemotherapy (P = .016). There was increased toxicity, including a higher rate of treatment-related grade 3 to 5 bleeding events (6.7% v 0.5%; P < .001) and treatment-related deaths (9.3% v 3.5%; P = .022) with BC versus chemotherapy. CONCLUSION: The addition of bevacizumab to chemotherapy did not improve OS but improved the response rate and progression-free survival with increased toxicities. These results encourage biomarker-driven studies of angiogenesis inhibitors with better toxicity profiles in select patients with SCCHN.

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