靶向治疗的KRAS基因（原文此处缺失KRAS）突变转移性结直肠癌患者的缓解深度和早期肿瘤缩小的预后影响
Prognostic impact of depth of response and early tumour shrinkage in patients with -mutated metastatic colorectal cancer treated with targeted therapy.
作者信息
Vetere Guglielmo, Germani Marco Maria, Antoniotti Carlotta, Salvatore Lisa, Pietrantonio Filippo, Lonardi Sara, Bensi Maria, Ghelardi Filippo, Calegari Maria Alessandra, Intini Rossana, Minelli Alessandro, Sullo Francesco Giulio, Boccaccio Chiara, Taravella Ada, Puccini Alberto, Lavacchi Daniele, Noto Laura, Salati Massimiliano, Scartozzi Mario, Cremolini Chiara
机构信息
Department of Translational Research and New Technologies in Medicine and Surgery, University of Pisa, Pisa, Italy.
Unit of Medical Oncology 2, Azienda Ospedaliero-Universitaria Pisana, Pisa, Italy.
出版信息
Ther Adv Med Oncol. 2025 Jan 7;17:17588359241299975. doi: 10.1177/17588359241299975. eCollection 2025.
BACKGROUND
Encorafenib plus cetuximab (EC) is the standard of care for pre-treated mutated metastatic colorectal cancer (mCRC). Depth of response (DpR) and early tumour shrinkage (ETS) previously showed a strong correlation with survival outcomes of first-line chemotherapy ± biological agents.
OBJECTIVES
We aimed to assess potential predictors of primary resistance to EC ± binimetinib (B) and relationships of DpR/ETS with survival outcomes and clinical characteristics.
DESIGN
This is a retrospective real-world cohort study of mutated mCRC patients treated with second-line EC ± B at 20 Italian centres.
METHODS
Measurable disease according to Response Evaluation Criteria In Solid Tumour (RECIST) 1.1 at baseline and at least one subsequent computed tomography (CT) scan were mandatory for inclusion. Clinical features associated with primary resistance, DpR and ETS were investigated. Relationships of DpR and ETS, both as binary, according to conventional (30% for DpR and 20% for ETS) and median cut-off values, and continuous variables, with progression-free (PFS), overall survival (OS) and duration of response (DoR) were assessed in non-primary resistant patients.
RESULTS
A total of 105 patients were included. The primary resistance rate was 28% (29/105) and was associated with baseline peritoneal metastases ( = 0.04). Disease control and overall response rates were 72% (76/105) and 24% (25/105), respectively, with a median DpR of 15% and an ETS rate of 37% (28/76). Mucinous histology was associated with a significantly lower magnitude of DpR ( = 0.005) and a lower rate of ETS ( = 0.002). In the multivariable models, DpR significantly correlated with longer PFS as a dichotomous variable, according both to conventional (hazard ratio (HR) : 0.52, 95% CI: 0.30-0.90, = 0.02) and median cut-off values (HR: 0.55, 95% CI: 0.33-0.92, = 0.03), and as a continuous variable (HR per 10% increment: 0.88, 95% CI: 0.78-0.98, = 0.02), while correlations with OS were not confirmed. DpR was also significantly associated with longer DoR ( = 0.04; = 0.04; = 0.02), whereas no relationships of ETS with PFS, OS or DoR were detected.
CONCLUSION
A DpR of at least 15% independently predicts PFS benefit in mutated mCRC patients treated with second-line EC ± B.
背景
恩考芬尼联合西妥昔单抗（EC）是经治的KRAS突变型转移性结直肠癌（mCRC）的标准治疗方案。反应深度（DpR）和早期肿瘤缩小（ETS）此前显示与一线化疗±生物制剂的生存结果密切相关。
目的
我们旨在评估对EC±比尼美替尼（B）原发性耐药的潜在预测因素，以及DpR/ETS与生存结果和临床特征的关系。
设计
这是一项在意大利20个中心对接受二线EC±B治疗的KRAS突变型mCRC患者进行的回顾性真实世界队列研究。
方法
纳入标准为基线时根据实体瘤疗效评价标准（RECIST）1.1可测量疾病，且至少有一次后续计算机断层扫描（CT）扫描。研究与原发性耐药、DpR和ETS相关的临床特征。在非原发性耐药患者中，评估DpR和ETS作为二元变量（根据传统标准（DpR为30%，ETS为20%）和中位数临界值）以及连续变量与无进展生存期（PFS）、总生存期（OS）和缓解持续时间（DoR）的关系。
结果
共纳入105例患者。原发性耐药率为28%（29/105），与基线腹膜转移相关（P=0.04）。疾病控制率和总缓解率分别为72%（76/105）和24%（25/105），中位DpR为15%，ETS率为37%（28/76）。黏液性组织学与显著更低的DpR幅度（P=0.005）和更低的ETS率（P=0.002）相关。在多变量模型中，DpR作为二分变量与更长的PFS显著相关，根据传统标准（风险比（HR）：0.52，95%CI：0.30-0.90，P=0.02）和中位数临界值（HR：0.55，95%CI：0.33-0.92，P=0.03），以及作为连续变量（每增加10%的HR：0.88，95%CI：0.78-0.98，P=0.02），而与OS的相关性未得到证实。DpR也与更长的DoR显著相关（P=0.04；P=0.04；P=0.02），而未检测到ETS与PFS、OS或DoR的关系。
结论
至少15%的DpR可独立预测接受二线EC±B治疗的KRAS突变型mCRC患者的PFS获益。
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