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背景与目的鼠类肉瘤病毒癌基因(Kirsten rat sarcoma viral oncogene,KRAS)是非小细胞肺癌(non-small cell lung cancer,NSCLC)的重要驱动基因之一,研究显示KRAS是表皮生长因子受体酪氨酸激酶抑制剂(epidermal growth factor receptor tyrosine kinase inhibitors,EGFR-TKIs)药物的耐药标志,但其对于化疗敏感性及预后方面的意义存在争议。本研究旨在积累KRAS突变阳性的NSCLC患者治疗经验。方法我们回顾性分析了107例KRAS突变阳性的NSCLC患者的临床资料,分析KRAS突变阳性的NSCLC患者一线化疗疗效以及靶向治疗疗效。结果 52例接受一线化疗的晚期KRAS突变阳性NSCLC患者客观缓解率(objective response rate,ORR)为9.6%,疾病控制率(disease control rate,DCR)为53.8%,中位疾病无进展生存期(progression-free survival,PFS)为3个月;21例接受EGFR-TKIs药物治疗的KRAS突变阳性NSCLC患者ORR为9.5%,DCR为23.8%,PFS为1个月,其中EGFR/KRAS共突变患者接受EGFR-TKIs治疗的ORR及DCR均要显著高于单纯KRAS突变人群(50%vs 0,P=0.029;75%vs 11.8%,P=0.043),EGFR/KRAS共突变患者接受EGFR-TKIs治疗的PFS较单纯KRAS突变患者延长,可见统计学差异(3个月vs 1个月,P=0.004)。结论 KRAS突变阳性NSCLC患者化疗有效率低,缓解时间短,EGFR-TKIs治疗效果差,亟需研发新的药物;EGFR/KRAS共突变现象客观存在,EGFR-TKIs药物可作为这类患者有效的治疗选择之一。
BACKGROUND & OBJECTIVE: Kirsten rat sarcoma viral oncogene (KRAS) is one of the most important driving factors in non-small cell lung cancer (NSCLC). KRAS is an epidermal growth factor receptor tyrosinase There are controversies about the significance of chemosensitivity and prognosis in the drug resistance markers of epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs). This study aimed to accumulate KRAS mutation-positive patients with NSCLC treatment experience. Methods We retrospectively analyzed the clinical data of 107 patients with KRAS mutation-positive NSCLC and analyzed the efficacy of first-line chemotherapy and targeted therapy in patients with KRAS-positive NSCLC. Results The objective response rate (ORR) of 52 patients with advanced KRAS mutation-positive NSCLC receiving first-line chemotherapy was 9.6%, the disease control rate (DCR) was 53.8%. The median progression-free survival -free survival (PFS) was 3 months. The KRAS mutation-positive NSCLC patients treated with EGFR-TKIs had ORR of 9.5%, DCR of 23.8%, PFS of 1 month, EGFR / KRAS co-mutation patients receiving EGFR (P = 0.029; 75% vs 11.8%, P = 0.043). The PFS of patients with EGFR / KRAS co-mutation treated with EGFR-TKIs was significantly higher than that of patients with KRAS alone Compared with patients with KRAS mutations alone, there was statistical difference (3 months vs 1 month, P = 0.004). Conclusion The chemotherapy of KRAS mutation-positive patients with NSCLC is ineffective, with short response time and poor therapeutic effect of EGFR-TKIs, so it is urgent to develop new drugs. The co-mutation of EGFR / KRAS objectively exists and EGFR-TKIs drugs can be used as effective treatment for these patients Choose one.