638P - Molecular marker analyses of EGFR and KRAS from the randomized phase II study of nimotuzumab In locally advanced esophageal cancer (NICE trial)

Date 29 September 2014
Event ESMO 2014
Session Poster Display session
Topics Anti-Cancer Agents & Biologic Therapy
Oesophageal Cancer
Translational Research
Presenter Gilberto De Castro Jr.
Citation Annals of Oncology (2014) 25 (suppl_4): iv210-iv253. 10.1093/annonc/mdu334
Authors G. De Castro Jr.1, N. Skare2, J.G.M. Segalla3, S. Azevedo4, C.J. Andrade5, D. Grabarz6, B. Franca7, A. Del Giglio8, N. Lazaretti9, M.N. Álvares10, J.L. Pedrini11, C. Kussumoto12, J.N.D. Matos Neto13, N. Forones14, H. Fernandes Jr.15, G. Borges16, G.C. Girotto17, L.P.D.G. Neusquen18, I. Dale19
  • 1Oncologia Clínica, ICESP - Instituto do Câncer do Estado de São Paulo, 01246-000 - Sao Paulo/BR
  • 2Oncology, Hospital Erasto Gaertner, Curitiba/BR
  • 3Clinical Oncology, Fundation Amaral Carvalho Hospital of Jau, 17210-080 - Jau/BR
  • 4Clinical Hematology And Oncology, Hospital de Clinicas de Porto Alegre, Porto Alegre/BR
  • 5Clinical Oncology, Instituto Nacional de Câncer (INCa), Rio de Janeiro/BR
  • 6Radioterapia, Hospital de Moji das Cruzes, Moji das Cruzes/BR
  • 7Oncologia Clinica - Predio 3, 4o Andar, Hospital Geral de Bonsucesso, 21041-030 - Rio de Janeiro/BR
  • 8Oncologia Clinica, Faculdade de Medicina do ABC, 09060650 - Santo Andre/BR
  • 9Oncology, Hospital da Cidade de Passo Fundo, Passo Fundo/BR
  • 10Oncology, Santa Casa de Belo Horizonte, Belo Horizonte/BR
  • 11Oncology, Hospital Nossa Senhora da Conceição, Porto Alegre/BR
  • 12Oncology, Hospital Municipal São José, Joinville/BR
  • 13Oncology, Hospital Universitario de Brasilia, 70910-900 - Brasilia/BR
  • 14Gastroenterology, Universidade Federal de São Paulo - UNIFESP, Sao Paulo/BR
  • 15Oncology, Consultoria em Estudos de Investigação Clínica, Sao Paulo/BR
  • 16Oncology, Centro de Novos Tratamentos, Itajaí/BR
  • 17Centro Integrado De Pesquisa (cip), Hospital de Base de Sao Jose do Rio Preto, 15090-000 - Sao Jose do Rio Preto/BR
  • 18Clinical Research, Eurofarma Laboratórios S.A., Sao Paulo/BR
  • 19Pathology, Universidade Federal de São Paulo - UNIFESP, Sao Paulo/BR

Abstract

Aim

NICE trial showed that combination of chemoradiation and nimotuzumab, a humanized antibody against EGFR, is safe and appears to increase the combined complete response (cCR) rate, defined as endoscopic and/or pathologic CR, in pts with locally advanced esophageal cancer (ASCO 2014). Here we present the results of the exploratory analyses of molecular markers and their correlation to clinical outcomes.

Methods

Tumor samples were obtained before chemoradiation with or without nimotuzumab. All samples were formalin-fixed and paraffin-embedded. Tumor areas were selected and macrodissected, followed by whole DNA extraction and amplification by PCR. Mutations and single nucleotide polymorphisms (SNPs) were searched in codons 12 and 13 of exon 2 for KRAS, and exons 18 to 24 for EGFR through DNA sequencing by Sangeŕs methodology. Fisher's exact test was used to compare groups.

Results

Molecular analyses were performed in tumor samples from 51 of the 107 randomized patients, 18 from the control arm (chemoradiation) and 37 from the experimental arm (chemoradiation plus nimotuzumab). No mutations or SNPs were identified in KRAS among the 48 samples analyzed. Indeed, no mutations were found in EGFR, but some SNPs were identified. Except for exon 21, for all other sequenced exons at least one patient had one SNP identified, more frequently in exons 20 and 23. SNPs identified in exon 20 included 167339G > A (rs10251977) and 167339G > A (rs1050171). The latter was the most frequent detected SNP and it was identified in 11 patients (3 in the control group and 8 in the nimotuzumab group). Within each treatment arm, the cCR rates were similar between patients whose tumors harboring or not the SNP rs1050171. Although not statistically significant (P = 0.074), in the nimotuzumab group, cCR rate of tumors harboring rs1050171 was nominally higher than the rate observed for tumors without this SNP (87.5% [7/8] vs. 42.9% [6/14]).

Conclusions

No mutations were found in KRAS or EGFR. Several EGFR SNPs were identified, being rs1050171 in exon 20 the most frequently found. Although exploratory, these results suggest an association between response to nimotuzumab and tumor biologic characteristics. Further exploration of this hypothesis is planned in a phase III trial.

Disclosure

L.P.D.G. Neusquen: Clinical Research Department of Eurofarma S.A. All other authors have declared no conflicts of interest.