Ciracì Paolo, Studiale Vittorio, Taravella Ada, Antoniotti Carlotta, Cremolini Chiara
Unit of Medical Oncology 2, Azienda Ospedaliera Universitaria Pisana, Pisa, Italy.
Department of Translational Research and New Technologies in Medicine and Surgery, University of Pisa, Pisa, Italy.
Nat Rev Clin Oncol. 2025 Jan;22(1):28-45. doi: 10.1038/s41571-024-00965-0. Epub 2024 Nov 18.
Over the past few years, several novel systemic treatments have emerged for patients with treatment-refractory metastatic colorectal cancer, thus making selection of the most effective later-line therapy a challenge for medical oncologists. Over the past decade, regorafenib and trifluridine-tipiracil were the only available drugs and often provided limited clinical benefit compared to best supportive care. Results from subsequent practice-changing trials opened several novel therapeutic avenues, both for unselected patients (such as trifluridine-tipiracil plus bevacizumab or fruquintinib) and for subgroups defined by the presence of actionable alterations in their tumours (such as HER2-targeted therapies or KRAS inhibitors) or with no acquired mechanisms of resistance to the previously received targeted agents in circulating tumour DNA (such as retreatment with anti-EGFR antibodies). In this Review, we provide a comprehensive overview of advances in the field over the past few years and offer a practical perspective on translation of the most relevant results into the daily management of patients with metastatic colorectal cancer using an evidence-based algorithm. Finally, we discuss some of the most appealing ongoing areas of research and highlight approaches with the potential to further expand the therapeutic armamentarium.
在过去几年中，针对难治性转移性结直肠癌患者出现了几种新型全身治疗方法，这使得为医学肿瘤学家选择最有效的后线治疗成为一项挑战。在过去十年中，瑞戈非尼和曲氟尿苷-替匹嘧啶是仅有的可用药物，与最佳支持治疗相比，其临床获益往往有限。随后改变实践的试验结果开辟了几条新的治疗途径，既适用于未选择的患者（如曲氟尿苷-替匹嘧啶联合贝伐单抗或呋喹替尼），也适用于根据肿瘤中存在可操作改变定义的亚组患者（如HER2靶向治疗或KRAS抑制剂），或循环肿瘤DNA中对先前接受的靶向药物无获得性耐药机制的患者（如用抗EGFR抗体再次治疗）。在本综述中，我们全面概述了该领域过去几年的进展，并就如何使用基于证据的算法将最相关的结果转化为转移性结直肠癌患者的日常管理提供了实用观点。最后，我们讨论了一些最具吸引力的正在进行的研究领域，并强调了有可能进一步扩大治疗手段的方法。
