EGFR expression and survival in patients given cetuximab and chemoradiation for stage III non-small cell lung cancer: a secondary analysis of RTOG 0324

Radiother Oncol. 2014 Jul;112(1):30-6. doi: 10.1016/j.radonc.2014.06.012. Epub 2014 Jul 16.

Abstract

Purpose: We investigated whether expression of epidermal growth factor receptor (EGFR) was associated with survival and disease control in this secondary analysis of a phase II trial of cetuximab+chemoradiation for stage III non-small cell lung cancer.

Methods: Patients received cetuximab weekly before and during radiation (63 Gy/35 fractions/7 weeks) with weekly carboplatin + paclitaxel. We analyzed EGFR expression by immunohistochemistry (IHC) and fluorescence in situ hybridization (FISH) in pretreatment biopsy specimens and compared findings with overall and progression-free survival (OS, PFS) and time to progression (TTP).

Results: Specimens for IHC and FISH were collected from 51 and 45 of 87 evaluable patients. Pretreatment characteristics did not differ for patients with (n = 51) or without (n= 36) EGFR IHC data, or with (n = 45) or without (n = 42) FISH data. However, patients without IHC data had worse OS (HR = 1.63, P = 0.05), worse PFS (HR = 1.88, P = 0.008), and worse TTP [HR = 1.99, P = 0.01] than those with IHC data. EGFR protein expression was not related to pretreatment characteristics or OS; FISH-positive disease was associated with better performance status but not with OS, PFS, or TTP.

Conclusions: Surprisingly, outcomes differed not by EGFR expression but by the availability of samples for analysis, underscoring the importance of obtaining biopsy samples in such trials.

Keywords: Cetuximab; Clinical trials identifier NCT00081302; Erbitux; Inoperable lung cancer; RTOG 0324.

Publication types

  • Clinical Trial, Phase II
  • Randomized Controlled Trial
  • Research Support, N.I.H., Extramural

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Antibodies, Monoclonal, Humanized / administration & dosage
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use*
  • Carboplatin / administration & dosage
  • Carcinoma, Non-Small-Cell Lung / metabolism*
  • Carcinoma, Non-Small-Cell Lung / mortality
  • Carcinoma, Non-Small-Cell Lung / therapy
  • Cetuximab
  • Chemoradiotherapy
  • Disease-Free Survival
  • ErbB Receptors / metabolism*
  • Female
  • Humans
  • Immunohistochemistry
  • In Situ Hybridization, Fluorescence
  • Lung Neoplasms / metabolism*
  • Lung Neoplasms / mortality
  • Lung Neoplasms / therapy
  • Male
  • Middle Aged
  • Paclitaxel / administration & dosage
  • Prognosis
  • Treatment Outcome

Substances

  • Antibodies, Monoclonal, Humanized
  • Carboplatin
  • ErbB Receptors
  • Paclitaxel
  • Cetuximab