化疗药物对KRAS突变转移性非小细胞肺癌患者生存的影响

Mustafa Emre Duygulu, Atila Yildirim, Eyyup Ayas, Nese Alyildiz, Sevdegul Aydin Mungan, Evren Fidan
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The cases were classified into five subgroups based on the chemotherapy regimens (platinum + gemcitabine, platinum + taxane, platinum + pemetrexed, platinum + vinorelbine, and others). The clinical and demographic data of 41 cases were analyzed retrospectively, and survival analyses were performed using the Kaplan–Meier method. Results Thirty-seven of 41 patients (90.2%) were males, and 27 (65.9%) had adenocarcinoma histology. The most prevalent mutation was KRAS G12C, with 12 cases (29.2%), followed by KRAS G12V, with 9 cases (21.9%). Other mutations were as follows: KRAS G12D 4 (9%), KRAS G13C 3 (7.3%), KRAS G12A 2 (4.8%), KRAS G12R 2 (4.8%), KRAS Q61H 2 (4.8%), KRAS Q61L 2 (4.8%), KRAS V14I 2 (4.8%), KRAS A146T 1 (2.4%), KRAS G13G 1 (2.4%), and KRAS G1C 1 (2.4%). The median progression-free survival (mPFS) for all groups was 4.6 months (95% confidence interval [CI]: 2.7-6.5), and there were no statistically significant differences between the groups (p = 0.121). The median overall survival (mOS) for all groups was 9.3 months (95% CI: 3.8–14.5), and there were no statistically significant differences between the groups (p = 0.805). Conclusions OS and PFS analyses showed no differences between platinum + taxane, platin + pemetrexed, platinum + gemcitabine, and platin + vinorelbine used in first-line treatments for KRAS mutant NSCLC cases. 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引用次数: 0

摘要

KRAS突变在高达30%的非小细胞肺癌(NSCLC)病例中观察到,并与不良预后相关。在KRAS p.G12C突变和一线化疗(±免疫治疗)耐药的病例中,可选择靶向药物。本研究旨在探讨kras突变的转移性非小细胞肺癌患者一线化疗药物与治疗反应的相关性。材料和方法对2019年1月至2021年12月在本中心诊断为转移性NSCLC的病例进行回顾性数据库检索,使用下一代测序(NGS)方法发现KRAS突变阳性。根据化疗方案(铂+吉西他滨、铂+紫杉烷、铂+培美曲塞、铂+长春瑞滨等)将病例分为5个亚组。回顾性分析41例患者的临床及人口学资料,采用Kaplan-Meier法进行生存分析。结果41例患者中男性37例(90.2%),27例(65.9%)有腺癌组织学。KRAS G12C突变最多,共12例(29.2%),KRAS G12V突变次之,共9例(21.9%)。其他突变如下:KRAS g12d1(9%)、KRAS g13c3(7.3%)、KRAS g12a2(4.8%)、KRAS g12r2(4.8%)、KRAS Q61H 2(4.8%)、KRAS q61l2(4.8%)、KRAS V14I 2(4.8%)、KRAS a146t1(2.4%)、KRAS g13g1(2.4%)和KRAS G1C 1(2.4%)。所有组的中位无进展生存期(mPFS)为4.6个月(95%可信区间[CI]: 2.7-6.5),组间差异无统计学意义(p = 0.121)。各组患者的中位总生存期(mOS)为9.3个月(95% CI: 3.8 ~ 14.5),组间差异无统计学意义(p = 0.805)。结论OS和PFS分析显示,铂+紫杉烷、铂+培美曲塞、铂+吉西他滨和铂+长春瑞滨在KRAS突变型NSCLC的一线治疗中没有差异。我们认为,患者的特异性特征可能是选择化疗的决定性因素。
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The Effect of Chemotherapeutic Agents on Survival in Metastatic Non-Small-Cell Lung Cancer with KRAS Mutation
Abstract Introduction KRAS mutation is observed in up to 30% of non-small-cell lung cancer (NSCLC) cases and is corelated with a poor prognosis. In the cases with KRAS p.G12C mutation and first-line chemotherapy (± immunotherapy) resistance, a targeted drug option is available. Objectives Our study aimed to examine the correlation between first-line chemotherapy agents and treatment response in patients with KRAS-mutated metastatic NSCLC. Materials and Methods Retrospective database searches were performed on cases diagnosed with metastatic NSCLC at our center between January 2019 and December 2021 that were found to be KRAS mutation positive using the next-generation sequencing (NGS) approach. The cases were classified into five subgroups based on the chemotherapy regimens (platinum + gemcitabine, platinum + taxane, platinum + pemetrexed, platinum + vinorelbine, and others). The clinical and demographic data of 41 cases were analyzed retrospectively, and survival analyses were performed using the Kaplan–Meier method. Results Thirty-seven of 41 patients (90.2%) were males, and 27 (65.9%) had adenocarcinoma histology. The most prevalent mutation was KRAS G12C, with 12 cases (29.2%), followed by KRAS G12V, with 9 cases (21.9%). Other mutations were as follows: KRAS G12D 4 (9%), KRAS G13C 3 (7.3%), KRAS G12A 2 (4.8%), KRAS G12R 2 (4.8%), KRAS Q61H 2 (4.8%), KRAS Q61L 2 (4.8%), KRAS V14I 2 (4.8%), KRAS A146T 1 (2.4%), KRAS G13G 1 (2.4%), and KRAS G1C 1 (2.4%). The median progression-free survival (mPFS) for all groups was 4.6 months (95% confidence interval [CI]: 2.7-6.5), and there were no statistically significant differences between the groups (p = 0.121). The median overall survival (mOS) for all groups was 9.3 months (95% CI: 3.8–14.5), and there were no statistically significant differences between the groups (p = 0.805). Conclusions OS and PFS analyses showed no differences between platinum + taxane, platin + pemetrexed, platinum + gemcitabine, and platin + vinorelbine used in first-line treatments for KRAS mutant NSCLC cases. We believe that patient-specific characteristics may be a determining factor in selecting chemotherapy for this patient population.
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期刊介绍: The journal will cover technical and clinical studies related to medical and pediatric oncology in human well being including ethical and social issues. Articles with clinical interest and implications will be given preference.
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