Cisplatin, 5-fluorouracil, and cetuximab (PFE) with or without cilengitide in recurrent/metastatic squamous cell carcinoma of the head and neck: Results of the randomized phase I/II ADVANTAGE trial (phase II part)

J. B. Vermorken, F. Peyrade, J. Krauss, R. Mesía, E. Remenár, T. C. Gauler, U. Keilholz, J. P. Delord, P. Schafhausen, J. Erfán, T. H. Brümmendorf, L. Iglesias, U. Bethe, C. Hicking, P. M. Clement

Research output: Contribution to journalArticle

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Abstract

Background: Recurrent and/or metastatic squamous cell carcinoma of the head and neck (R/M-SCCHN) overexpresses αvβ5 integrin. Cilengitide selectively inhibits αvβ3 and αvβ5 integrins and is investigated as a treatment strategy. Patients and methods: The phase I/II study ADVANTAGE evaluated cilengitide combined with cisplatin, 5-fluorouracil, and cetuximab (PFE) in R/M-SCCHN. The phase II part reported here was an open-label, randomized, controlled trial investigating progression-free survival (PFS). Patients received up to six cycles of PFE alone or combined with cilengitide 2000 mg once (CIL1W) or twice (CIL2W) weekly. Thereafter, patients received maintenance therapy (cilengitide arms: cilengitide plus cetuximab; PFE-alone arm: cetuximab only) until disease progression or unacceptable toxicity. Results: One hundred and eighty-two patients were treated. Median PFS per investigator read was similar for CIL1W + PFE, CIL2W + PFE, and PFE alone (6.4, 5.6, and 5.7 months, respectively). Accordingly, median overall survival and objective response rates were not improved with cilengitide (12.4 months/47%, 10.6 months/27%, and 11.6 months/36%, respectively). No clinically meaningful safety differences were observed between groups. None of the tested biomarkers (expression of integrins, CD31, Ki-67, vascular endothelial growth factor receptor 2, vascular endothelial-cadherin, type IV collagen, epidermal growth factor receptor, or p16 for human papillomavirus) were predictive of outcome. Conclusion: Neither of the cilengitide-containing regimens demonstrated a PFS benefit over PFE alone in R/M-SCCHN patients.

Original languageEnglish
Article numbermdu003
Pages (from-to)682-688
Number of pages7
JournalAnnals of Oncology
Volume25
Issue number3
DOIs
Publication statusPublished - Mar 2014

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Fluorouracil
Cisplatin
Integrins
Disease-Free Survival
Vascular Endothelial Growth Factor Receptor-2
Collagen Type IV
Cilengitide
Carcinoma, squamous cell of head and neck
Cetuximab
Epidermal Growth Factor Receptor
Disease Progression
Randomized Controlled Trials
Biomarkers
Research Personnel
Safety
Survival
Therapeutics

Keywords

  • Cetuximab
  • Cilengitide
  • Integrin inhibitor
  • Phase I/II
  • Platinum-based chemotherapy with 5-fluorouracil
  • Recurrent and/or metastatic squamous cell carcinoma of the head and neck (R/M-SCCHN)

ASJC Scopus subject areas

  • Oncology
  • Hematology

Cite this

Cisplatin, 5-fluorouracil, and cetuximab (PFE) with or without cilengitide in recurrent/metastatic squamous cell carcinoma of the head and neck : Results of the randomized phase I/II ADVANTAGE trial (phase II part). / Vermorken, J. B.; Peyrade, F.; Krauss, J.; Mesía, R.; Remenár, E.; Gauler, T. C.; Keilholz, U.; Delord, J. P.; Schafhausen, P.; Erfán, J.; Brümmendorf, T. H.; Iglesias, L.; Bethe, U.; Hicking, C.; Clement, P. M.

In: Annals of Oncology, Vol. 25, No. 3, mdu003, 03.2014, p. 682-688.

Research output: Contribution to journalArticle

Vermorken, JB, Peyrade, F, Krauss, J, Mesía, R, Remenár, E, Gauler, TC, Keilholz, U, Delord, JP, Schafhausen, P, Erfán, J, Brümmendorf, TH, Iglesias, L, Bethe, U, Hicking, C & Clement, PM 2014, 'Cisplatin, 5-fluorouracil, and cetuximab (PFE) with or without cilengitide in recurrent/metastatic squamous cell carcinoma of the head and neck: Results of the randomized phase I/II ADVANTAGE trial (phase II part)', Annals of Oncology, vol. 25, no. 3, mdu003, pp. 682-688. https://doi.org/10.1093/annonc/mdu003
Vermorken, J. B. ; Peyrade, F. ; Krauss, J. ; Mesía, R. ; Remenár, E. ; Gauler, T. C. ; Keilholz, U. ; Delord, J. P. ; Schafhausen, P. ; Erfán, J. ; Brümmendorf, T. H. ; Iglesias, L. ; Bethe, U. ; Hicking, C. ; Clement, P. M. / Cisplatin, 5-fluorouracil, and cetuximab (PFE) with or without cilengitide in recurrent/metastatic squamous cell carcinoma of the head and neck : Results of the randomized phase I/II ADVANTAGE trial (phase II part). In: Annals of Oncology. 2014 ; Vol. 25, No. 3. pp. 682-688.
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abstract = "Background: Recurrent and/or metastatic squamous cell carcinoma of the head and neck (R/M-SCCHN) overexpresses αvβ5 integrin. Cilengitide selectively inhibits αvβ3 and αvβ5 integrins and is investigated as a treatment strategy. Patients and methods: The phase I/II study ADVANTAGE evaluated cilengitide combined with cisplatin, 5-fluorouracil, and cetuximab (PFE) in R/M-SCCHN. The phase II part reported here was an open-label, randomized, controlled trial investigating progression-free survival (PFS). Patients received up to six cycles of PFE alone or combined with cilengitide 2000 mg once (CIL1W) or twice (CIL2W) weekly. Thereafter, patients received maintenance therapy (cilengitide arms: cilengitide plus cetuximab; PFE-alone arm: cetuximab only) until disease progression or unacceptable toxicity. Results: One hundred and eighty-two patients were treated. Median PFS per investigator read was similar for CIL1W + PFE, CIL2W + PFE, and PFE alone (6.4, 5.6, and 5.7 months, respectively). Accordingly, median overall survival and objective response rates were not improved with cilengitide (12.4 months/47{\%}, 10.6 months/27{\%}, and 11.6 months/36{\%}, respectively). No clinically meaningful safety differences were observed between groups. None of the tested biomarkers (expression of integrins, CD31, Ki-67, vascular endothelial growth factor receptor 2, vascular endothelial-cadherin, type IV collagen, epidermal growth factor receptor, or p16 for human papillomavirus) were predictive of outcome. Conclusion: Neither of the cilengitide-containing regimens demonstrated a PFS benefit over PFE alone in R/M-SCCHN patients.",
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T1 - Cisplatin, 5-fluorouracil, and cetuximab (PFE) with or without cilengitide in recurrent/metastatic squamous cell carcinoma of the head and neck

T2 - Results of the randomized phase I/II ADVANTAGE trial (phase II part)

AU - Vermorken, J. B.

AU - Peyrade, F.

AU - Krauss, J.

AU - Mesía, R.

AU - Remenár, E.

AU - Gauler, T. C.

AU - Keilholz, U.

AU - Delord, J. P.

AU - Schafhausen, P.

AU - Erfán, J.

AU - Brümmendorf, T. H.

AU - Iglesias, L.

AU - Bethe, U.

AU - Hicking, C.

AU - Clement, P. M.

PY - 2014/3

Y1 - 2014/3

N2 - Background: Recurrent and/or metastatic squamous cell carcinoma of the head and neck (R/M-SCCHN) overexpresses αvβ5 integrin. Cilengitide selectively inhibits αvβ3 and αvβ5 integrins and is investigated as a treatment strategy. Patients and methods: The phase I/II study ADVANTAGE evaluated cilengitide combined with cisplatin, 5-fluorouracil, and cetuximab (PFE) in R/M-SCCHN. The phase II part reported here was an open-label, randomized, controlled trial investigating progression-free survival (PFS). Patients received up to six cycles of PFE alone or combined with cilengitide 2000 mg once (CIL1W) or twice (CIL2W) weekly. Thereafter, patients received maintenance therapy (cilengitide arms: cilengitide plus cetuximab; PFE-alone arm: cetuximab only) until disease progression or unacceptable toxicity. Results: One hundred and eighty-two patients were treated. Median PFS per investigator read was similar for CIL1W + PFE, CIL2W + PFE, and PFE alone (6.4, 5.6, and 5.7 months, respectively). Accordingly, median overall survival and objective response rates were not improved with cilengitide (12.4 months/47%, 10.6 months/27%, and 11.6 months/36%, respectively). No clinically meaningful safety differences were observed between groups. None of the tested biomarkers (expression of integrins, CD31, Ki-67, vascular endothelial growth factor receptor 2, vascular endothelial-cadherin, type IV collagen, epidermal growth factor receptor, or p16 for human papillomavirus) were predictive of outcome. Conclusion: Neither of the cilengitide-containing regimens demonstrated a PFS benefit over PFE alone in R/M-SCCHN patients.

AB - Background: Recurrent and/or metastatic squamous cell carcinoma of the head and neck (R/M-SCCHN) overexpresses αvβ5 integrin. Cilengitide selectively inhibits αvβ3 and αvβ5 integrins and is investigated as a treatment strategy. Patients and methods: The phase I/II study ADVANTAGE evaluated cilengitide combined with cisplatin, 5-fluorouracil, and cetuximab (PFE) in R/M-SCCHN. The phase II part reported here was an open-label, randomized, controlled trial investigating progression-free survival (PFS). Patients received up to six cycles of PFE alone or combined with cilengitide 2000 mg once (CIL1W) or twice (CIL2W) weekly. Thereafter, patients received maintenance therapy (cilengitide arms: cilengitide plus cetuximab; PFE-alone arm: cetuximab only) until disease progression or unacceptable toxicity. Results: One hundred and eighty-two patients were treated. Median PFS per investigator read was similar for CIL1W + PFE, CIL2W + PFE, and PFE alone (6.4, 5.6, and 5.7 months, respectively). Accordingly, median overall survival and objective response rates were not improved with cilengitide (12.4 months/47%, 10.6 months/27%, and 11.6 months/36%, respectively). No clinically meaningful safety differences were observed between groups. None of the tested biomarkers (expression of integrins, CD31, Ki-67, vascular endothelial growth factor receptor 2, vascular endothelial-cadherin, type IV collagen, epidermal growth factor receptor, or p16 for human papillomavirus) were predictive of outcome. Conclusion: Neither of the cilengitide-containing regimens demonstrated a PFS benefit over PFE alone in R/M-SCCHN patients.

KW - Cetuximab

KW - Cilengitide

KW - Integrin inhibitor

KW - Phase I/II

KW - Platinum-based chemotherapy with 5-fluorouracil

KW - Recurrent and/or metastatic squamous cell carcinoma of the head and neck (R/M-SCCHN)

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