Benefit from anti-EGFRs in <i>RAS</i> and <i>BRAF</i> wild-type metastatic transverse colon cancer: a clinical and molecular proof of concept study.
Di Donato, S
de Braud, F
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<h4>Objective</h4>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.<h4>Methods</h4>Patients with <i>RAS/BRAF</i> 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.<h4>Results</h4>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 <i>MET</i> amplification and an <i>ERBB4</i> S303F substitution were detected in patients with rapid disease progression, while others had PRESSING panel-negative tumours with CMS2 or CMS4 subtypes.<h4>Conclusions</h4><i>RAS/BRAF</i> wild-type MSS mTCCs may be sensitive to anti-EGFRs, as confirmed by molecular analyses.
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Systems and Precision Cancer Medicine
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ESMO open, 2019, 4 (2), pp. e000489 - ?