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
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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.
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p53 co-mutations were not prognostic or predictive in multiple analyses.
“Unexpectedly, p53 co-mutations were not prognostic or predictive in multiple analyses [56–58].”
From Drugging KRAS: Current perspectives and state-of-art review (2022) · cites this paper as [57]
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- Authors
- Shepherd, F. A., Lacas, B., Le Teuff, G., Hainaut, P., Jänne, P. A., Pignon, J.-P., Le Chevalier, T., Seymour, L., Douillard, J.-Y., Graziano, S., Brambilla, E., Pirker, R., Filipits, M., Kratzke, R., Soria, J.-C., Tsao, M.-S., & on behalf of the LACE-Bio Collaborative Group
- Affiliations
- University of Toronto (CA)
- Frances A. Shepherd and Ming-Sound Tsao, Princess Margaret Cancer Centre; University of Toronto, Toronto; Lesley Seymour, Queen’s University, Kingston, Ontario, Canada; Benjamin Lacas, Gwénaël Le Teuff, Jean-Pierre Pignon, Thierry Le Chevalier, and Jean-Charles Soria, Institut Gustave-Roussy; Benjamin Lacas, Gwénaël Le Teuff, Jean-Pierre Pignon, Thierry Le Chevalier, and Jean-Charles Soria, University Paris XI, Paris; Pierre Hainaut, International Agency for Research on Cancer, Lyon; Jean-Yves Douillard,...
- ORCID
- Venue
- Journal of Clinical Oncology
- Published
- 2017-06-20
- Volume
- 35
- Issue
- 18
- Pages
- 2018-2027
- ISSN
- 0732-183X (ISSN-L)
- 1527-7755
- PMC
- PMC6075828
- OpenAlex
- W2609015711
- Cited by
- 124
- References
- 43
- Citations by year
- 2026: 5 · 2025: 3 · 2024: 13 · 2023: 17 · 2022: 13 · 2021: 16 · 2020: 25 · 2019: 16 · 2018: 13 · 2017: 3
- FWCI
- 12.89
- Type
- journal article
- Language
- en
- Open access
- green
- europepmc.org
- Locations
- Journal of Clinical Oncology (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- World Health Organization
- American Society of Clinical Oncology
- National Cancer Institute (R01CA165958)
- Topics
- Health Sciences › Medicine › Pulmonary and Respiratory Medicine › Lung Cancer Treatments and Mutations
- Health Sciences › Medicine › Pulmonary and Respiratory Medicine › Lung Cancer Diagnosis and Treatment
- Health Sciences › Medicine › Oncology › Lung Cancer Research Studies
- Keywords
- TP53 mutation, KRAS mutation, EGFR mutation, non-small cell lung cancer, early-stage lung cancer, adjuvant chemotherapy, prognostic factors, predictive biomarkers, adenocarcinoma, overall survival, disease-free survival, tumor suppressor, oncogenic mutations
- MeSH terms
- Adenocarcinoma, Antineoplastic Combined Chemotherapy Protocols, Carcinoma, Non-Small-Cell Lung, DNA Mutational Analysis, Female, Humans, Lung Neoplasms, Male, Middle Aged, Mutation, Neoplasm Staging, Predictive Value of Tests, Survival Rate, Randomized Controlled Trials as Topic, Tumor Suppressor Protein p53, Proto-Oncogene Proteins p21(ras), Chemotherapy, Adjuvant, Disease-Free Survival, ErbB Receptors
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