Department of Translational Research and New Technologies in Medicine and Surgery, Unit of Medical Oncology 2, Azienda Ospedaliera Universitaria Pisana, Pisa, Italy.
Medical Oncology Department, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy.
Clin Colorectal Cancer. 2020 Sep;19(3):191-199.e6. doi: 10.1016/j.clcc.2020.03.009. Epub 2020 Apr 11.
On the basis of retrospective analyses and phase 2 studies, metastatic colorectal cancer patients whose disease responded to a first-line regimen containing an anti-epidermal growth factor receptor (EGFR) agent may experience benefit from anti-EGFR readministration in later therapy lines. While the analysis of circulating tumor DNA seems a promising tool to select the best candidates for this strategy, identifying clinical predictors of anti-EGFR sensitivity would be useful to drive treatment choices in daily practice.
A real-life database of 5530 patients treated at 6 institutions was queried. Included were patients who were retreated with anti-EGFRs, who had RAS/BRAF wild-type-status tissue samples, who had received a first-line anti-EGFR-based regimen with at least stable disease as best response, and who had received at least one further line of therapy before anti-EGFR retreatment. The association with overall response rate (ORR), progression-free survival (PFS), and overall survival (OS) of variables potentially related to anti-EGFR sensitivity was investigated.
A total of 86 patients were identified. The ORR during anti-EGFR retreatment was 19.8%; median PFS and OS were 3.8 and 10.2 months, respectively. No significant association of clinical features of anti-EGFR sensitivity with ORR, PFS, and OS was observed. Among the 56 patients with a time from the last anti-EGFR administration to first-line progressive disease of < 3 months (rechallenge group), > 2 prior therapy lines and a longer anti-EGFR-free interval were associated with higher ORR, but not with longer PFS or OS.
Clinical features we deemed surrogates of anti-EGFR sensitivity were not reliable predictors of benefit from anti-EGFR retreatment.
基于回顾性分析和 2 期研究，对一线治疗方案中含有抗表皮生长因子受体（EGFR）药物且疾病有反应的转移性结直肠癌患者，在后续治疗中再次使用 EGFR 拮抗剂可能会获益。虽然循环肿瘤 DNA 的分析似乎是选择该策略最佳候选者的有前途的工具，但确定抗 EGFR 敏感性的临床预测因素将有助于在日常实践中做出治疗选择。
查询了 6 个机构的 5530 名患者的真实数据库。纳入的患者接受了抗 EGFR 治疗的再治疗，具有 RAS/BRAF 野生型组织样本，接受了一线基于 EGFR 的方案治疗，且最佳反应为稳定疾病，且在抗 EGFR 再治疗前至少接受了一线治疗。研究了与潜在的抗 EGFR 敏感性相关的变量与总缓解率（ORR）、无进展生存期（PFS）和总生存期（OS）的相关性。
共鉴定出 86 名患者。抗 EGFR 再治疗期间的 ORR 为 19.8%；中位 PFS 和 OS 分别为 3.8 个月和 10.2 个月。未观察到临床特征与 ORR、PFS 和 OS 之间存在显著关联。在最后一次抗 EGFR 给药至一线进展的时间<3 个月的 56 名患者（再挑战组）中，>2 个先前的治疗线和更长的抗 EGFR 无治疗间隔与更高的 ORR 相关，但与更长的 PFS 或 OS 无关。
我们认为是抗 EGFR 敏感性的临床特征不能可靠预测抗 EGFR 再治疗的获益。
