Division of Medical Oncology and Hematology, Princess Margaret Cancer Centre, University Health Network and Department of Medicine, University of Toronto, Toronto, ON, Canada; Multidisciplinary Oncology and Therapeutic Innovations Department, Aix Marseille University, Assistance Publique Hôpitaux de Marseille, Marseille, France.
Division of Medical Oncology and Hematology, Princess Margaret Cancer Centre, University Health Network and Department of Medicine, University of Toronto, Toronto, ON, Canada; Multidisciplinary Oncology and Therapeutic Innovations Department, Aix Marseille University, Assistance Publique Hôpitaux de Marseille, Marseille, France.
Clin Lung Cancer. 2019 May;20(3):e338-e345. doi: 10.1016/j.cllc.2018.12.009. Epub 2018 Dec 19.
KRAS and TP53 are common mutations in non-small-cell lung cancer (NSCLC). The Lung Adjuvant Cisplatin Evaluation Biological Program group found adjuvant chemotherapy to be deleterious in patients with coexisting KRAS/TP53 mutations.
To validate these results, patients with NSCLC tested for KRAS and TP53 mutations and receiving chemotherapy for any stage NSCLC were selected. Mutation status was analyzed using next generation sequencing (Illumina) or multiplex recurrent mutation detection (MassARRAY, Agena Biosciences) assays, and was correlated with clinical and demographic data. Disease-free (DFS) or progression-free survival (PFS) was the main endpoint, and overall survival (OS) was the secondary endpoint.
Among 218 patients, 28 had coexisting KRAS/TP53 mutations, 77 TP53, 37 KRAS, 76 had neither KRAS nor TP53 mutation (WT/WT). There was no DFS/PFS difference for the KRAS/TP53 group versus all others among 99 patients who received adjuvant chemotherapy (hazard ratio [HR], 1.22; 95% confidence interval [CI], 0.61-2.44; P = .57), 27 stage III patients who received chemo-radiation (HR, 0.87; 95% CI, 0.32-2.38; P = .8), and 63 patients who received palliative chemotherapy (HR, 0.68; 95% CI, 0.31-1.48; P = .33). OS was longer in the WT/WT group compared with any other group (KRAS: HR, 1.87; 95% CI, 1.02-3.43; P = .043; TP53: HR, 2.17; 95% CI, 1.3-3.61; P = .0028; KRAS/TP53: HR, 2.06; 95% CI, 1.09-3.88; P = .026). No OS difference was seen for KRAS/TP53 compared with the other groups (HR, 1.26; 95% CI, 0.75-2.13; P = .38).
There was no significant difference in DFS/PFS between the 4 groups. However, OS was longer for patients with TP53 and KRAS wild-type NSCLC who received chemotherapy for any stage compared with patients with KRAS, TP53 mutation, or double mutant tumors.
KRAS 和 TP53 是常见的非小细胞肺癌（NSCLC）突变。肺癌辅助顺铂评估生物计划组发现，同时存在 KRAS/TP53 突变的患者接受辅助化疗有害。
为了验证这些结果，选择了接受 NSCLC 治疗且同时存在 KRAS 和 TP53 突变的 NSCLC 患者，以及接受任何阶段 NSCLC 化疗的患者。使用下一代测序（Illumina）或多重复发突变检测（MassARRAY、Agena Biosciences）检测突变状态，并将其与临床和人口统计学数据相关联。无病（DFS）或无进展生存期（PFS）是主要终点，总生存期（OS）是次要终点。
在 218 名患者中，28 名患者同时存在 KRAS/TP53 突变，77 名患者存在 TP53 突变，37 名患者存在 KRAS 突变，76 名患者既不存在 KRAS 也不存在 TP53 突变（WT/WT）。在接受辅助化疗的 99 名患者中，KRAS/TP53 组与其他所有患者之间的 DFS/PFS 无差异（危险比 [HR]，1.22；95%置信区间 [CI]，0.61-2.44；P = 0.57），在接受化疗放疗的 27 名 III 期患者中（HR，0.87；95%CI，0.32-2.38；P = 0.8），以及在接受姑息化疗的 63 名患者中（HR，0.68；95%CI，0.31-1.48；P = 0.33）。与任何其他组相比，WT/WT 组的 OS 更长（KRAS：HR，1.87；95%CI，1.02-3.43；P = 0.043；TP53：HR，2.17；95%CI，1.3-3.61；P = 0.0028；KRAS/TP53：HR，2.06；95%CI，1.09-3.88；P = 0.026）。与其他组相比，KRAS/TP53 组的 OS 没有差异（HR，1.26；95%CI，0.75-2.13；P = 0.38）。
4 组之间 DFS/PFS 无显著差异。然而，与 KRAS、TP53 突变或双突变肿瘤患者相比，接受任何阶段化疗的 TP53 和 KRAS 野生型 NSCLC 患者的 OS 更长。
