Xiao Annie, Fakih Marwan
Department of Medical Oncology and Therapeutics Research, City of Hope Comprehensive Cancer Center, Duarte, CA, USA.
J Gastrointest Oncol. 2025 Feb 28;16(1):292-300. doi: 10.21037/jgo-24-458. Epub 2025 Feb 26.
Anti-epidermal growth factor receptor (EGFR) therapies are important targeted agents in the treatment of metastatic colorectal cancer (CRC). However, clinical benefit is limited to patients with left-sided primary tumors and RAS wild-type (WT) disease. In right-sided chemo-refractory settings, response to anti-EGFR therapy has not been reported to date.
We present a case of a 70-year-old man with metachronous metastatic ascending colon adenocarcinoma who experienced an exceptional response to FOLFIRI (fluorouracil, leucovorin, and irinotecan) plus panitumumab after failing multiple lines of therapy. He was initially diagnosed with stage IIIB (pT4aN1M0) disease and underwent hemicolectomy followed by adjuvant FOLFOX (fluorouracil, leucovorin, and oxaliplatin). Nine months after completion of adjuvant therapy, disease recurred in the liver, peritoneum, and mesenteric lymph nodes. Subsequent treatments included FOLFIRI plus bevacizumab and FOLFOX with eventual progression. Tumor genomic profiling revealed RAS/RAF WT disease, and in the absence of anti-EGFR therapy resistance mutations, the patient was offered treatment with FOLFIRI plus panitumumab. He achieved immediate palliation of his abdominal pain after one cycle, followed by normalization of his tumor markers and significant tumor regression of his hepatic, peritoneal, lung, and distant lymph node metastases within four cycles.
Treatment options for right-sided RAS-WT metastatic CRC are limited, particularly after progression on standard chemotherapies. While anti-EGFR antibodies have demonstrated detrimental survival impact in the first-line setting for right-sided CRC, their performance in later lines is less well-characterized. This case challenges the notion of right-sided disease as uniformly resistant to EGFR inhibition and highlights the need for additional biomarker studies to identify the subset of right-sided CRC that may benefit from EGFR targeted strategies. Emerging evidence suggests that more stringent genomic criteria for EGFR resistance, beyond RAS mutation status alone, may refine patient selection for benefit from anti-EGFR therapies.
抗表皮生长因子受体（EGFR）疗法是转移性结直肠癌（CRC）治疗中的重要靶向药物。然而，临床获益仅限于左侧原发性肿瘤且RAS野生型（WT）疾病的患者。在右侧化疗难治性情况下，迄今为止尚未报道对抗EGFR治疗的反应。
我们报告一例70岁男性患者，患有异时性转移性升结肠癌，在多线治疗失败后，对FOLFIRI（氟尿嘧啶、亚叶酸钙和伊立替康）联合帕尼单抗产生了显著反应。他最初被诊断为IIIB期（pT4aN1M0）疾病，接受了半结肠切除术，随后进行辅助FOLFOX（氟尿嘧啶、亚叶酸钙和奥沙利铂）治疗。辅助治疗完成9个月后，疾病在肝脏、腹膜和肠系膜淋巴结复发。后续治疗包括FOLFIRI联合贝伐单抗以及FOLFOX，最终疾病进展。肿瘤基因组分析显示为RAS/RAF WT疾病，且不存在抗EGFR治疗耐药突变，该患者接受了FOLFIRI联合帕尼单抗治疗。一个周期后他的腹痛立即得到缓解，随后肿瘤标志物恢复正常，四个周期内肝脏、腹膜、肺部和远处淋巴结转移灶出现显著肿瘤消退。
右侧RAS-WT转移性CRC的治疗选择有限，尤其是在标准化疗进展后。虽然抗EGFR抗体在右侧CRC一线治疗中已显示出对生存有不利影响，但其在后续治疗中的表现特征尚不明确。该病例挑战了右侧疾病对EGFR抑制普遍耐药的观念，并强调需要进行更多生物标志物研究，以确定可能从EGFR靶向策略中获益的右侧CRC亚组。新出现的证据表明，除了RAS突变状态外，更严格的EGFR耐药基因组标准可能会优化患者选择，使患者从抗EGFR治疗中获益。
