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.

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

Cremolini, Chiara;Rossini, Daniele;Loupakis, Fotios;Schirripa, Marta;Borelli, Beatrice;Falcone, Alfredo;
2019-01-01

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.
Cremolini, Chiara; Benelli, Matteo; Fontana, Elisa; Pagani, Filippo; Rossini, Daniele; Fucà, Giovanni; Busico, Adele; Conca, Elena; Di Donato, Samantha; Loupakis, Fotios; Schirripa, Marta; Lonardi, Sara; Borelli, Beatrice; Ongaro, Elena; Eason, Katherine; Morano, Federica; Casagrande, Mariaelena; Fassan, Matteo; Sadanandam, Anguraj; De Braud, Filippo; Falcone, Alfredo; Pietrantonio, Filippo
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11568/990322
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