Dataset Information

A Real-World Study in Advanced Non-Small Cell Lung Cancer with KRAS Mutations.

ABSTRACT: BACKGROUND:KRAS gene mutations are well known as a key driver of advanced non-small cell lung cancer (NSCLC). The impact of KRAS-mutant subtypes on the survival benefit from salvage chemotherapy is controversial. Here, we present a real-world study in patients across China with advanced NSCLC with KRAS mutations using a website-based patient self-report system. METHODS:We identified a total of 75 patients diagnosed with KRAS-mutant (determined by molecular sequencing) advanced NSCLC between 2014/5/9 and 2019/5/30. KRAS mutation subtypes were divided into G12C and non-G12C groups for statistical analysis. The clinicopathological characteristics and treatment survival benefit in all patients with a KRAS mutation were evaluated. Programmed death-ligand 1 (PD-L1) expression data were collected from 30 patients in the same cohort. RESULTS:In this study, 23 patients with stage IIIB NSCLC and 52 patients with stage IV NSCLC were enrolled with 58 men and 17 women; the median age was 60 years (39-84). All patients received regular chemotherapy/radiotherapy/targeted therapy/immune therapy as per the disease condition. Four main KRAS mutation subtypes were detected: G12C (33%), G12V (19%), G12A (12%), and G12D (12%). Three predominant KRAS comutations were detected: TP53-KRAS (31%), EGFR-KRAS (11%), and STK11-KRAS (8%). Compared with the KRAS non-G12C mutation subtype, patients with the KRAS G12C mutation had potentially longer progression-free survival (PFS) after first-line chemotherapy (4.7 vs. 2.5 months, p < 0.05). Pemetrexed-based chemotherapy appeared to be superior to taxanes- and gemcitabine-based chemotherapies in all patients (PFS: 5.0 vs. 1.5 and 2.3 months, respectively, p > 0.05). Cox regression analysis showed that the KRAS G12C mutation and pemetrexed-based first-line chemotherapy were positive influencers for PFS after first-line (hazard ratios = 0.31 and 0.55, respectively, P < 0.05), but not second-line chemotherapies. CONCLUSION:The KRAS G12C mutation could be a predictive biomarker for better survival benefit from first-line chemotherapy in patients with advanced NSCLC and KRAS mutations. The first-line chemotherapy regimen could possibly influence the outcome in patients with KRAS mutations. Larger and prospective clinical trials are warranted to confirm our conclusions.

SUBMITTER: Lei L

PROVIDER: S-EPMC7031095 | biostudies-literature | 2020 Feb

REPOSITORIES: biostudies-literature

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A Real-World Study in Advanced Non-Small Cell Lung Cancer with KRAS Mutations.

Lei Lei L Wang Wen-Xian WX Yu Zong-Yang ZY Liang Xian-Bin XB Pan Wei-Wei WW Chen Hua-Fei HF Wang Li-Ping LP Fang Yong Y Wang Min M Xu Chun-Wei CW Fang Mei-Yu MY

Translational oncology 20191224 2

<h4>Background</h4>KRAS gene mutations are well known as a key driver of advanced non-small cell lung cancer (NSCLC). The impact of KRAS-mutant subtypes on the survival benefit from salvage chemotherapy is controversial. Here, we present a real-world study in patients across China with advanced NSCLC with KRAS mutations using a website-based patient self-report system.<h4>Methods</h4>We identified a total of 75 patients diagnosed with KRAS-mutant (determined by molecular sequencing) advanced NSC ...[more]

PMID: 31881505

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Project description:BACKGROUND:The objective of this study was to describe the real-world treatment and overall survival (OS) of German patients with a diagnosis of advanced non-small cell lung cancer (aNSCLC), and to explore factors associated with the real-world mortality risk. METHODS:This was a retrospective German claims data analysis of incident aNSCLC patients. Data were available from 01/01/2011 until 31/12/2016. Identification of eligible patients took place between 01/01/2012-31/12/2015, to allow for at least 1-year pre-index and follow-up periods. Inpatient and outpatient mutation test procedures after aNSCLC diagnosis were observed. Further, prescribed treatments and OS since first (incident) aNSCLC diagnosis and start of respective treatment lines were described both for all patients and presumed EGFR/ALK/ROS-1-positive patients. Factors associated with OS were analyzed in multivariable Cox regression analysis. RESULTS:Overall, 1741 aNSCLC patients were observed (mean age: 66·97?years, female: 29·87%). The mutation test rate within this population was 26·31% (n?=?458), 26·6% of these patients (n?=?122) received a targeted treatment and were assumed to have a positive EGFR/ALK/ROS-1 test result. Most often prescribed treatments were pemetrexed monotherapy as 1?L (21·23% for all and 11·11% for mutation-positive patients) and erlotinib monotherapy as 2?L (25·83%/38·54%). Median OS since incident diagnosis was 351?days in all and 571?days in mutation-positive patients. In a multivariable Cox regression analysis, higher age, a stage IV disease, a higher number of chronic drugs in the pre-index period and no systemic therapy increased the risk of early death since first aNSCLC diagnosis. On the other hand, female gender and treatment with therapies other than chemotherapy were associated with a lower risk of early death. CONCLUSIONS:Despite the introduction of new treatments, the real-world survival prognosis for aNSCLC patients remains poor if measured based on an unselected real-world population of patients. Still, the majority of German aNSCLC patients do not receive a mutation test.

Dataset Information

A Real-World Study in Advanced Non-Small Cell Lung Cancer with KRAS Mutations.

Publications

A Real-World Study in Advanced Non-Small Cell Lung Cancer with KRAS Mutations.

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