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

Eur Arch Otorhinolaryngol. 2019 Feb;276(2):541-550. doi: 10.1007/s00405-018-5235-6. Epub 2018 Dec 6.

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

MeSH terms

  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use*
  • Carboplatin / administration & dosage
  • Cetuximab / administration & dosage
  • Cisplatin / administration & dosage
  • Female
  • Fluorouracil / administration & dosage
  • Head and Neck Neoplasms / drug therapy*
  • Head and Neck Neoplasms / genetics
  • Head and Neck Neoplasms / mortality
  • Humans
  • Male
  • Middle Aged
  • Neoplasm Recurrence, Local
  • Progression-Free Survival
  • Proto-Oncogene Proteins p21(ras) / genetics*
  • Retrospective Studies

Substances

  • KRAS protein, human
  • Carboplatin
  • Proto-Oncogene Proteins p21(ras)
  • Cetuximab
  • Cisplatin
  • Fluorouracil