Benefit from anti-EGFRs in RAS and BRAF wild-type metastatic transverse colon cancer: A clinical and molecular proof of concept study

Chiara Cremolini, Matteo Benelli, Elisa Fontana, Filippo Pagani, Daniele Rossini, Giovanni Fucà, Adele Busico, Elena Conca, Samantha Di Donato, Fotios Loupakis, Marta Schirripa, Sara Lonardi, Beatrice Borelli, Elena Ongaro, Katherine Eason, Federica Morano, Mariaelena Casagrande, Matteo Fassan, Anguraj Sadanandam, Filippo De BraudAlfredo Falcone, Filippo Pietrantonio

Research output: Contribution to journalArticlepeer-review

Abstract

Objective Primary tumour location is regarded as a reliable surrogate of colorectal cancer biology. Sensitivity to anti-EGFRs (Epidermal Growth Factor Receptor) of metastatic transverse colon cancers (mTCCs) has usually been assumed similar to right-sided tumours; however, evidence about the clinical behaviour of mTCC is limited. Thus, to verify sensitivity of mTCC to anti-EGFRs we conducted the present study. Methods Patients with RAS/BRAF wild-type microsatellite stable (MSS) mTCC receiving anti-EGFR monotherapy, or in combination with irinotecan if clearly irinotecan-refractory, were included. Hypothesising an overall response rate (ORR) of 35%, 11 patients, of whom at least 3 were responders, were necessary to be able to reject the null hypothesis of an ORR of 5%, with α and β errors of 0.05 and 0.20. PRESSING panel and consensus molecular subtypes (CMS) were assessed on tumour samples, whereas in-silico data were obtained from TCGA dataset. Results Among nine eligible patients, four and three achieved response and disease stabilisation (ORR 44%). At a median follow-up of 23.1 months, median progression-free survival and overall survival were 7.3 (95% CI 3.9 to NA) and 15.0 months (95% CI 10.0 to NA), respectively. A MET amplification and an ERBB4 S303F substitution were detected in patients with rapid disease progression, while others had PRESSING panel-negative tumours with CMS2 or CMS4 subtypes. Conclusions RAS/BRAF wild-type MSS mTCCs may be sensitive to anti-EGFRs, as confirmed by molecular analyses.

Original languageEnglish
Article numbere000489
Pages (from-to)1-7
Number of pages7
JournalESMO Open
Volume4
Issue number2
DOIs
Publication statusPublished - Mar 1 2019

Keywords

  • anti-EGFR, RAS and BRAF mutations
  • CMS subtypes
  • PRESSING panel
  • transverse colon cancer

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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