Department of Experimental and Clinical Medicine, University of Florence.
Medical Oncology, Azienda Ospedaliero-Universitaria Careggi, Florence.
Anticancer Drugs. 2020 Oct;31(9):979-982. doi: 10.1097/CAD.0000000000000923.
Since the introduction of antiepidermal growth factor receptor (anti-EGFR) monoclonal antibodies (moAbs), the treatment of metastatic colorectal cancer (mCRC) has become crucially dependent on the mutation profile of the tumour over the last two decades. Recently, rechallenge strategy with cetuximab-based chemotherapy has demonstrated to be active in a subgroup of patients whose tumour maintained wild-type RAS and RAF status. In this setting, liquid biopsy may replace tissue sample for the identification of specific subgroups of pretreated patients that may benefit from the reintroduction of anti-EGFR moAbs. In November 2014, a 64-year-old man with IVB stage BRAF, KRAS and NRAS wild-type mCRC was admitted in our hospital. He received FOLFIRI cetuximab as first-line treatment with deep and long-lasting partial response (PR), followed by cetuximab maintenance therapy until January 2016. At the time of disease progression, FOLFIRI cetuximab regimen was reintroduced resulting in stabilization of disease and he continued with capecitabine cetuximab therapy until disease progression in October 2016. Then, the patient consecutively received FOLFOX bevacizumab, TAS-102, regorafenib and FOLFIRI followed by de Gramont maintenance treatment. Finally, he was retreated with FOLFIRI cetuximab with disease progression within 3 months and died in May 2019. During his clinical course, liquid biopsy detected two mutations: one in KRAS Cd.12 and one in NRAS Cd. 61. The longitudinal assessment of RAS status offers considerable advantages in order to avoid side effects and economic costs for ineffective treatment choices. Liquid biopsy could help better monitor the disease and provide molecularly guided treatments.
自引入抗表皮生长因子受体（anti-EGFR）单克隆抗体（moAbs）以来，过去二十年中，转移性结直肠癌（mCRC）的治疗已严重依赖于肿瘤的突变谱。最近，基于西妥昔单抗的化疗再挑战策略已证明对肿瘤维持野生型 RAS 和 RAF 状态的亚组患者有效。在这种情况下，液体活检可能会替代组织样本，用于鉴定可能受益于重新引入抗 EGFR moAbs 的预处理患者的特定亚组。2014 年 11 月，一名 64 岁男性患有 IVB 期 BRAF、KRAS 和 NRAS 野生型 mCRC，收入我院。他接受 FOLFIRI 西妥昔单抗一线治疗，获得深度和持久的部分缓解（PR），随后接受西妥昔单抗维持治疗，直至 2016 年 1 月。在疾病进展时，重新引入 FOLFIRI 西妥昔单抗方案，使疾病稳定，他继续接受卡培他滨西妥昔单抗治疗，直至 2016 年 10 月疾病进展。随后，患者连续接受 FOLFOX 贝伐珠单抗、TAS-102、regorafenib 和 FOLFIRI 序贯 de Gramont 维持治疗。最后，他再次接受 FOLFIRI 西妥昔单抗治疗，但在 3 个月内疾病进展，并于 2019 年 5 月死亡。在他的临床病程中，液体活检检测到两个突变：一个在 KRAS Cd.12，一个在 NRAS Cd.61。RAS 状态的纵向评估具有很大的优势，可以避免无效治疗选择的副作用和经济成本。液体活检可以帮助更好地监测疾病并提供分子指导治疗。
