Department of Medical Oncology and Therapeutics Research, City of Hope Comprehensive Cancer Center, Duarte, CA, USA.
Oncologist. 2022 Mar 4;27(2):104-109. doi: 10.1093/oncolo/oyab028.
Limited studies have suggested that mucinous histology is associated an attenuated response to anti-epidermal growth factor receptor (EGFR) therapy.
We conducted a single-institution, retrospective study to review the anti-EGFR response and the molecular profile of patients with left-sided microsatellite stable RAS/BRAF wild-type mucinous metastatic colorectal cancer.
In comparison to nonmucinous population (n = 98), mucinous histology (n = 20) was associated with a younger age (48 vs 54, P = .02), wild-type APC (80% vs 15.3%, P < .0001), and wild-type TP53 (40% vs 8.2%, P = .001). Guanine nucleotide binding protein, alpha stimulating (GNAS) mutations were exclusively found in mucinous tumors (20% vs 0, P < .0001). Genomic alterations associated with resistance to anti-EGFR therapy, such as ERBB2 amplification, PIK3CA mutation, MAP2K1 mutation, and KRAS amplification, were identified in patients with left-sided RAS/BRAF wild-type mucinous metastatic colorectal cancer. Mucinous histology was not associated with a worse outcome than non-mucinous histology (34.3 vs 42.2 months, P = .85). However, patients with left-sided RAS/BARF wild-type mucinous colorectal cancer treated with first-line anti-EGFR therapy had significantly worse progression-free survival (4 vs 6.5 months, hazard ratio [HR] = 5.3, 95% confidence interval [CI] 1.3-21.7, P = .01) than patients treated with the first-line vascular endothelial growth factor A antibody, bevacizumab. Anti-EGFR therapy was associated with limited responses and a short PFS across all lines of therapy in 12 patients with left-sided RAS/BRAF wild-type mucinous colorectal cancer.
Mucinous histology is associated with diminished benefits from anti-EGFR therapy in patients with left-sided RAS/BRAF wild-type colorectal cancer. These patients should be considered for bevacizumab-based therapy in the first- and second-line settings.
有限的研究表明，黏液组织学与抗表皮生长因子受体（EGFR）治疗的反应减弱有关。
我们进行了一项单机构、回顾性研究，以评估左侧微卫星稳定 RAS/BRAF 野生型黏液转移性结直肠癌患者的抗 EGFR 反应和分子特征。
与非黏液人群（n=98）相比，黏液组织学（n=20）与更年轻的年龄（48 岁 vs 54 岁，P=.02）、野生型 APC（80% vs 15.3%，P<.0001）和野生型 TP53（40% vs 8.2%，P=.001）相关。鸟苷酸结合蛋白，α 刺激（GNAS）突变仅在黏液肿瘤中发现（20% vs 0，P<.0001）。与抗 EGFR 治疗耐药相关的基因组改变，如 ERBB2 扩增、PIK3CA 突变、MAP2K1 突变和 KRAS 扩增，在左侧 RAS/BRAF 野生型黏液转移性结直肠癌患者中被发现。黏液组织学与非黏液组织学相比，结局并不差（34.3 个月 vs 42.2 个月，P=.85）。然而，接受一线抗 EGFR 治疗的左侧 RAS/BARF 野生型黏液结直肠癌患者的无进展生存期（PFS）明显更差（4 个月 vs 6.5 个月，风险比[HR] = 5.3，95%置信区间[CI] 1.3-21.7，P=.01），低于接受一线血管内皮生长因子 A 抗体贝伐珠单抗治疗的患者。在 12 例左侧 RAS/BRAF 野生型黏液结直肠癌患者中，抗 EGFR 治疗与所有治疗线的有限反应和较短的 PFS 相关。
黏液组织学与左侧 RAS/BRAF 野生型结直肠癌患者接受抗 EGFR 治疗的获益减少有关。这些患者应考虑在一线和二线治疗中使用贝伐珠单抗治疗。
