The prognostic impact of TP53 comutation in EGFR mutant lung cancer patients: a systematic review and meta-analysis

ABSTRACT

Background The prognostic value of TP53 commutation in epidermal growth factor receptor (EGFR) mutant lung cancer is controversial and we therefore conducted this systematic review and meta-analysis.

Methods A systematic search was carried out in Pubmed, Web of Science, the Cochrane Library, Medline and Embase up to 19 April 2018. The pooled hazard ratio (HR) of overall survival (OS) and progression-free survival (PFS), the relative risk (RR) of objective response rate (ORR) were calculated.

Results Overall, a total of eight studies comprising 2979 patients were included. When generally comparing TP53 mutation group with TP53 wild-type group, we confirmed the prognostic value of poor OS of TP53 in EGFR mutant lung cancers (HR 1.73, 95% CI 1.22–2.44, P = 0.002). In subgroup analysis of OS, the prognostic value was maintained in patients treated with EGFR tyrosine kinase inhibitors (TKIs) but not in those treated with non-targeted therapy (HR 2.29, 95% CI 1.39–3.76, P = 0.001), and was also maintained in patients with advanced-stage lung cancers rather than those of all stages (HR 2.00, 95% CI 1.11–3.61, P = 0.021). For patients treated with EGFR TKIs, TP53 commutation was predictive of a poor PFS (HR 2.18, 95% CI 1.42–3.36, P < 0.001) but the prognostic value on ORR was not observed (RR 1.15, 95% CI 0.92–1.44, P = 0.212). Additional subgroup analysis based on TP53 mutation subtypes was not pooled due to limited data.

Conclusion Generally we confirmed the prognostic value of poor OS and PFS of TP53 commutation in EGFR mutant lung cancers, and it should be further investigated and validated regarding the prognostic role of TP53 mutation subtypes.

KEYWORDS:

• Lung cancer
• TP53
• epidermal growth factor receptor
• prognosis

Acknowledgments

We thank Dr. Fenge Li for providing us raw data.

Declaration of interest

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties. Peer reviewers on this manuscript have no relevant financial relationships to disclose.

Supplementary material

Supplementary data for this article can be accessed here.

Additional information

Funding

This work was supported by the Transformation Projects of Sci-Tech Achievements of Sichuan Province (2016CZYD0001), the Sci-Tech Support Program of Science and Technology Department of Sichuan Province (2016SZ0073), the National Major Sci-Tech Project (2017ZX10103004-012) and the National Key Development Plan for Precision Medicine Research (2017YFC0910004).