野生型转移性横结肠癌中抗表皮生长因子受体（EGFR）的获益：一项临床及分子概念验证研究
Benefit from anti-EGFRs in and wild-type metastatic transverse colon cancer: a clinical and molecular proof of concept study.
作者信息
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
机构信息
Unit of Medical Oncology 2, Azienda Ospedaliero Universitaria Pisana, Pisa, Italy.
Department of Translational Research and New Technologies in Medicine and Surgery, University of Pisa, Pisa, Italy.
出版信息
ESMO Open. 2019 Mar 8;4(2):e000489. doi: 10.1136/esmoopen-2019-000489. eCollection 2019.
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 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 amplification and an S303F substitution were detected in patients with rapid disease progression, while others had PRESSING panel-negative tumours with CMS2 or CMS4 subtypes.
CONCLUSIONS
wild-type MSS mTCCs may be sensitive to anti-EGFRs, as confirmed by molecular analyses.
目的
原发肿瘤位置被视为结直肠癌生物学特性的可靠替代指标。转移性横结肠癌（mTCC）对抗表皮生长因子受体（EGFR）的敏感性通常被认为与右侧肿瘤相似；然而，关于mTCC临床行为的证据有限。因此，为验证mTCC对抗EGFR的敏感性，我们开展了本研究。
方法
纳入接受抗EGFR单药治疗，或在明确对伊立替康耐药时联合伊立替康治疗的野生型微卫星稳定（MSS）mTCC患者。假设总缓解率（ORR）为35%，为能够拒绝ORR为5%的零假设，需要11名患者，其中至少3名是缓解者，α和β错误分别为0.05和0.20。对肿瘤样本评估PRESSING面板和共识分子亚型（CMS），而从TCGA数据集中获取电子数据。
结果
9名符合条件的患者中，4名获得缓解，3名病情稳定（ORR 44%）。中位随访23.1个月时，中位无进展生存期和总生存期分别为7.3（95%CI 3.9至NA）和15.0个月（95%CI 10.0至NA）。在疾病快速进展的患者中检测到一个 扩增和一个S303F替代，而其他患者的肿瘤为PRESSING面板阴性，属于CMS2或CMS4亚型。
结论
分子分析证实，野生型MSS mTCCs可能对抗EGFR敏感。
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