Cambridge University Hospitals NHS Foundation Trust, Addenbrooke's Hospital, Cambridge, UK.
Expert Rev Anticancer Ther. 2021 May;21(5):535-546. doi: 10.1080/14737140.2021.1866548. Epub 2021 Jan 11.
Esophagogastric cancers remain a considerable health burden and among the top causes of global cancer-related deaths. Chemotherapy remains the cornerstone of treatment for patients with advanced disease. Doublet platinum/fluoropyrimidine therapy is established as first-line treatment with the option of adding a taxane in selected patients. Irinotecan, taxanes, and ramucirumab are approved as second-line treatments. Results from the trials KEYNOTE-059, ATTRACTION-2, and TAGS have established the use of immune checkpoint inhibitors and trifluridine/tipiracil as a third-line treatment. High PD-L1 expression, microsatellite instability, tumor mutational burden, and Epstein-Barr virus status may also be used to enrich for responses to immunotherapy.
In this review, we discuss the outcome of recent trials in the later lines of therapy for esophagogastric cancer and place these in the context of current treatment paradigms. We also discuss the biology of esophagogastric cancers and how this might inform the development of new treatments. Finally, we comment on promising new drugs in development.
Recent advances in the treatment of chemo-refractory esophagogastric cancer add to the improving survival of patients with this disease. Further research is needed to improve patient selection to therapies and the earlier incorporation of these agents in the treatment journey.
食管胃结合部癌仍是一个严重的健康负担，也是全球癌症相关死亡的主要原因之一。化疗仍然是晚期患者的治疗基石。含铂类/氟嘧啶类的双联化疗是首选治疗方案，部分患者可加用紫杉类药物。伊立替康、紫杉类药物和雷莫芦单抗已被批准作为二线治疗药物。KEYNOTE-059、ATTRACTION-2 和 TAGS 这三项试验的结果确立了免疫检查点抑制剂和替吡嘧啶/氟尿嘧啶作为三线治疗的地位。高 PD-L1 表达、微卫星不稳定性、肿瘤突变负荷和 EBV 状态也可用于富集免疫治疗的反应。
在这篇综述中，我们讨论了食管胃结合部癌后线治疗的最新试验结果，并将其置于当前治疗模式的背景下。我们还讨论了食管胃结合部癌的生物学特性，以及这如何为新疗法的开发提供信息。最后，我们对正在开发的有前途的新药进行了评论。
化疗耐药性食管胃结合部癌治疗的最新进展增加了此类疾病患者的生存改善。需要进一步的研究来改善对这些疗法的患者选择，并更早地将这些药物纳入治疗方案。
