Pooled Analysis of the Prognostic and Predictive Effects of TP53 Comutation Status Combined With KRAS or EGFR Mutation in Early-Stage Resected Non–Small-Cell Lung Cancer in Four Trials of Adjuvant Chemotherapy
| Autor: | Elizabeth Brambilla, Thierry Le Chevalier, Gwénaël Le Teuff, Benjamin Lacas, Pierre Hainaut, Robert A. Kratzke, Stephen L. Graziano, Martin Filipits, Ming-Sound Tsao, R. Pirker, Jean-Charles Soria, Jean-Yves Douillard, Frances A. Shepherd, Pasi A. Jänne, L. Seymour, Jean-Pierre Pignon |
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| Rok vydání: | 2017 |
| Předmět: |
Male
0301 basic medicine Oncology Cancer Research medicine.medical_specialty Lung Neoplasms endocrine system diseases DNA Mutational Analysis Adenocarcinoma medicine.disease_cause Disease-Free Survival Proto-Oncogene Proteins p21(ras) 03 medical and health sciences 0302 clinical medicine Predictive Value of Tests Carcinoma Non-Small-Cell Lung Internal medicine Antineoplastic Combined Chemotherapy Protocols medicine Carcinoma Humans Stage (cooking) Lung cancer neoplasms Survival rate Neoplasm Staging Randomized Controlled Trials as Topic business.industry Proportional hazards model ORIGINAL REPORTS Middle Aged medicine.disease ErbB Receptors Survival Rate 030104 developmental biology Chemotherapy Adjuvant 030220 oncology & carcinogenesis Predictive value of tests Mutation Female KRAS Tumor Suppressor Protein p53 business |
| Zdroj: | Journal of Clinical Oncology. 35:2018-2027 |
| ISSN: | 1527-7755 0732-183X |
| DOI: | 10.1200/jco.2016.71.2893 |
| Popis: | Purpose Our previous work evaluated individual prognostic and predictive roles of TP53, KRAS, and EGFR in non–small-cell lung cancer (NSCLC). In this analysis, we explore the prognostic and predictive roles of TP53/KRAS and TP53/EGFR comutations in randomized trials of adjuvant chemotherapy versus observation. Patients and Methods Mutation analyses (wild-type [WT] and mutant) for TP53, KRAS, and EGFR were determined in blinded fashion in multiple laboratories. Primary and secondary end points of pooled analysis were overall survival and disease-free survival. We evaluated the role of TP53/KRAS comutation in all patients and in the adenocarcinoma subgroup as well as the TP53/EGFR comutation in adenocarcinoma only through a multivariable Cox proportional hazards model stratified by trial. Results Of 3,533 patients with NSCLC, 1,181 (557 deaths) and 404 (170 deaths) were used for TP53/KRAS and TP53/EGFR analyses. For TP53/KRAS mutation status, no prognostic effect was observed ( P = .61), whereas a borderline predictive effect ( P = .04) was observed with a deleterious effect of chemotherapy with TP53/KRAS comutations versus WT/WT (hazard ratio, 2.49 [95% CI, 1.10 to 5.64]; P = .03). TP53/EGFR comutation in adenocarcinoma was neither prognostic ( P = .83), nor significantly predictive ( P = .86). Similar results were observed for both groups for disease-free survival. Conclusion We could identify no prognostic effect of the KRAS or EGFR driver and TP53 tumor suppressor comutation. Our observation of a potential negative predictive effect of TP53/KRAS comutation requires validation. |
| Databáze: | OpenAIRE |
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