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Benefit of cetuximab addition to a platinum–fluorouracil-based chemotherapy according to KRAS-LCS6 variant in an unselected population of recurrent and/or metastatic head and neck cancers

  • Vianney Bastit
  • Nicolas Bon-Mardion
  • Jean-Michel Picquenot
  • Vinciane Rainville
  • Cristian Moldovan
  • Arnaud François
  • Agnès Loeb
  • Sébastien Thureau
  • Dorel Manu
  • Fabrice Jardin
  • Jean-Paul Marie
  • Fréderic Di Fiore
  • Florian Clatot
Head & Neck
  • 9 Downloads

Abstract

Objectives

To evaluate the benefit of cetuximab (Cx) addition to platinum-based and 5-fluorouracil chemotherapy (PFU) in unselected recurrent and/or metastatic head and neck cancer patients (R/MHNC) according to KRAS-LCS6 variant status.

Methods

All patients who received at least two PFU ± Cx cycles from 2004 to 2014 were retrospectively included into to two distinct study periods according to Cx implementation: patients treated by PFU alone before 2009 and those treated by PFU + Cx from 2009. Primary objective was to evaluate the progression-free survival (PFS) between the two groups. Secondary objectives were to analyze the overall survival (OS) between the two groups and the prognostic impact of KRAS-LCS6 variant. Factors associated with survival were determined by a Cox multivariate analysis including age, WHO performance status (PS), type of treatment, KRAS-LCS6 variant, Charlson’s score and p16 status.

Results

Overall, 134 patients were included: 59 (44%) in PFU group and 75 (56%) in PFU + Cx group. Baseline characteristics were well balanced including 30% of patients with 2–3 PS. Median PFS was significantly improved in PFU + Cx group compared to PFU group (6.1 vs 4.4 months, respectively, HR 0.68, p = 0.02) and with a trend for better OS. A KRAS-LCS6 variant was found in 27 (25%) of samples without prognostic impact neither in whole population nor according to treatment. In multivariate analysis, addition of Cx to PFU was the only factor significantly associated with a better PFS (p = 0.01, HR 0.6).

Conclusion

Our results suggest that PFU + Cx combination may be effective in unselected population of R/MHNC regardless the KRAS-LCS6 variant status.

Keywords

Recurrent and/or metastatic head and neck cancers Cetuximab Unselected population KRAS-LCS6 Rs61764370 Prognosis 

Notes

Acknowledgements

The authors are grateful to Dr. M Bubenheim for his help in statistics and to Dr. T. Ducastelle for his help in collecting histological samples.

Funding

This is an academic research. Funding was provided by the Department of Medical Oncology of the Centre Henri Becquerel.

Compliance with ethical standards

Conflict of interest

The authors declare that they have no conflict of interest.

Supplementary material

405_2018_5235_MOESM1_ESM.docx (23 kb)
Supplementary material 1 (DOCX 22 KB)

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Copyright information

© Springer-Verlag GmbH Germany, part of Springer Nature 2018

Authors and Affiliations

  • Vianney Bastit
    • 1
    • 2
    • 9
  • Nicolas Bon-Mardion
    • 2
  • Jean-Michel Picquenot
    • 3
    • 4
  • Vinciane Rainville
    • 4
  • Cristian Moldovan
    • 5
  • Arnaud François
    • 6
  • Agnès Loeb
    • 7
  • Sébastien Thureau
    • 8
  • Dorel Manu
    • 1
  • Fabrice Jardin
    • 4
  • Jean-Paul Marie
    • 2
  • Fréderic Di Fiore
    • 4
    • 5
  • Florian Clatot
    • 4
    • 5
  1. 1.Department of Head and Neck SurgeryHenri Becquerel CentreRouenFrance
  2. 2.Department of Head and Neck SurgeryRouen University HospitalRouenFrance
  3. 3.Department of BiopathologyHenri Becquerel CentreRouenFrance
  4. 4.IRON Group, Normandy Centre for Genomic and Personalized Medicine, Rouen University Hospital, UNIROUEN, Inserm U1245, rue de GermontNormandie UniversitéRouenFrance
  5. 5.Department of Medical OncologyHenri Becquerel CentreRouenFrance
  6. 6.Department of BiopathologyRouen University HospitalRouenFrance
  7. 7.Department of Biomedical InformaticsHenri Becquerel CentreRouenFrance
  8. 8.Department of Radiation therapyHenri Becquerel CentreRouenFrance
  9. 9.Department of ENT and Head and Neck SurgeryCentre François BaclesseCaenFrance

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