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KRAS突变影响接受一线含铂化疗的非小细胞肺癌患者的预后。

KRAS mutations affect prognosis of non-small-cell lung cancer patients treated with first-line platinum containing chemotherapy.

作者信息

Marabese Mirko, Ganzinelli Monica, Garassino Marina C, Shepherd Frances A, Piva Sheila, Caiola Elisa, Macerelli Marianna, Bettini Anna, Lauricella Calogero, Floriani Irene, Farina Gabriella, Longo Flavia, Bonomi Lucia, Fabbri M Agnese, Veronese Silvio, Marsoni Silvia, Broggini Massimo, Rulli Eliana

机构信息

Oncology Department, IRCCS - Istituto di Ricerche Farmacologiche Mario Negri, Milan, Italy.

Oncology Department, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy.

出版信息

Oncotarget. 2015 Oct 20;6(32):34014-22. doi: 10.18632/oncotarget.5607.

Abstract

UNLABELLED

KRAS mutations seem to indicate a poor outcome in Non-Small-Cell Lung Cancer (NSCLC) but such evidence is still debated. The aim of this planned ancillary study within the TAILOR trial was to assess the prognostic value of KRAS mutations in advanced NSCLC patients treated with platinum-based first-line chemotherapy. Patients (N = 540), enrolled in the study in 52 Italian hospitals, were centrally genotyped twice in two independent laboratories for EGFR and KRAS mutational status.Of these, 247 patients were eligible and included in the present study. The primary endpoint was overall survival (OS) according to KRAS mutational status in patients harboring EGFR wild-type.Sixty (24.3%) out of 247 patients harbored KRAS mutations. Median OS was 14.3 months and 10.6 months in wild-type and mutated KRAS patients, respectively (unadjusted Hazard Ratio [HR]=1.41, 95%Confidence Interval [CI]: 1.03-1.94 P = 0.032; adjusted HR=1.39, 95%CI: 1.00-1.94 P = 0.050). This study, with all consecutive patients genotyped, indicates that the presence of KRAS mutations has a mild negative impact on OS in advanced NSCLC patient treated with a first-line platinum-containing regimen.

TRIAL REGISTRATION

clinicaltrials.gov identifierNCT00637910.

摘要

未标注

KRAS突变似乎预示着非小细胞肺癌(NSCLC)的预后不良,但此类证据仍存在争议。这项在TAILOR试验中计划开展的辅助研究的目的是评估KRAS突变对接受铂类一线化疗的晚期NSCLC患者的预后价值。在意大利52家医院入组该研究的患者(N = 540),在两个独立实验室进行了两次集中基因分型,以检测EGFR和KRAS的突变状态。其中,247例患者符合条件并纳入本研究。主要终点是EGFR野生型患者中根据KRAS突变状态的总生存期(OS)。247例患者中有60例(24.3%)存在KRAS突变。野生型和KRAS突变型患者的中位OS分别为14.3个月和10.6个月(未调整风险比[HR]=1.41,95%置信区间[CI]:1.03 - 1.94,P = 0.032;调整后HR=1.39,95%CI:1.00 - 1.94,P = 0.050)。这项对所有连续患者进行基因分型的研究表明,KRAS突变的存在对接受一线含铂方案治疗的晚期NSCLC患者的OS有轻度负面影响。

试验注册

clinicaltrials.gov标识符NCT00637910。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5a1c/4741822/d09e7e7a1bd0/oncotarget-06-34014-g001.jpg

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