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. 2022 Dec 12;14(24):6127.
doi: 10.3390/cancers14246127.

TP53 Co-Mutation Status Association with Clinical Outcomes in Patients with EGFR-Mutant Non-Small Cell Lung Cancer

Xiuning Le  1 , Cliff Molife  2 , Mark S Leusch  2 , Maria Teresa Rizzo  2 , Patrick M Peterson  2 , Nicola Caria  2 , Yongmei Chen  2 , Elena Gonzalez Gugel  2 , Carla Visseren-Grul  3
Affiliations

TP53 Co-Mutation Status Association with Clinical Outcomes in Patients with EGFR-Mutant Non-Small Cell Lung Cancer

Xiuning Le et al. Cancers (Basel). .

Abstract

TP53 co-mutations have shown association with poor prognosis in various solid tumors. For EGFR-mutated advanced non-small cell lung cancer (aNSCLC), conflicting results exist regarding its impact on survival. Clinical outcomes and genomic data were obtained retrospectively from the real-world (rw) de-identified clinicogenomic database. Patients who initiated therapy for EGFR-mutated aNSCLC between January 2014 and December 2020 were identified. Clinical outcomes were evaluated by TP53-mutational status. In 356 eligible EGFR-mutated aNSCLC patients (median age 68 years), 210 (59.0%) had TP53 co-mutation and 146 (41.0%) had TP53 wild-type tumor. Unadjusted analysis showed significantly shorter survival in patients with TP53 co-mutation versus TP53 wild-type (rw progression-free survival [rwPFS]: HR = 1.4, 95% CI 1.1-1.9, p = 0.0196; overall survival [OS]: HR = 1.6, 95% CI 1.1-2.2, p = 0.0088). Multivariable analysis confirmed independent association between TP53 co-mutation and worse rwPFS (HR = 1.4, 95% CI 1.0-0.9, p = 0.0280) and OS (HR = 1.4, 95% CI 1.0-2.0, p = 0.0345). Directionally consistent findings were observed for response rates, and subgroups by EGFR-activating mutation and first-line (1 L) therapy, with more pronounced negative effect in 1 L EGFR-TKI subgroup. TP53 co-mutations negatively affected survival in patients with EGFR-mutated aNSCLC receiving standard 1 L therapy in real-world practice.

Keywords: EGFR; EGFR-TKI; TP53; advanced non-small cell lung cancer; overall survival; progression-free survival.

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Conflict of interest statement

X.L. is employee at MD Anderson Cancer Center. She has received: (i) Grants: from Eli Lilly and Company, EMD Serono, Boehringer Ingelheim, Regeneron; (ii) Consulting fee: EMD Serono (Merck KGaA), AstraZeneca, Spectrum Pharmaceutics, Novartis, Eli Lilly, and Company, Boehringer Ingelheim, Hengrui Therapeutics, AstraZeneca, Janssen, Blueprint Medicines, Sensei Biotherapeutics, Abbvie and ArriVent; (iii) Support for attending meetings: Spectrum Therapeutics. CM, M.S.L., M.T.R., P.M.P., C.V.-G., Y.C., and EEG, are employees, and stockholders at Eli Lilly and Company. N.C. is a former employee at Eli Lilly and Company.

Figures

Figure 1
Figure 1
Patient inclusion/exclusion criteria and attrition.
Figure 2
Figure 2
rwPFS and OS—TP53 co-mutation vs. TP53 wild-type. (A) rwPFS. (B) OS.CI = confidence interval; HR = hazard ratio; OS = overall survival; rwPFS = real-world progression-free survival; TP53mt = TP53 co-mutation; TP53wt = TP53 wild-type. EGFR mutation includes both exon 19 and exon 21 mutations.
Figure 3
Figure 3
rwPFS and OS—TP53 co-mutation vs. TP53 wild-type by Exon19del mutation. (A) rwPFS. (B) OS. Unadjusted HR and 95% CI. CI = confidence interval; HR = hazard ratio; OS = overall survival; rwPFS = real-world progression-free survival; TP53mt = TP53 co-mutation; TP53wt = TP53 wild-type; exon 19 = exon 19 deletions.
Figure 3
Figure 3
rwPFS and OS—TP53 co-mutation vs. TP53 wild-type by Exon19del mutation. (A) rwPFS. (B) OS. Unadjusted HR and 95% CI. CI = confidence interval; HR = hazard ratio; OS = overall survival; rwPFS = real-world progression-free survival; TP53mt = TP53 co-mutation; TP53wt = TP53 wild-type; exon 19 = exon 19 deletions.
Figure 4
Figure 4
rwPFS and OS—TP53 co-mutation vs. TP53 wild-type by Exon21L858R mutation. (A) rwPFS. (B) OS. Unadjusted HR and 95% CI. CI = confidence interval; HR = hazard ratio; OS = overall survival; rwPFS = real-world progression-free survival; TP53mt = TP53 co-mutation; TP53wt = TP53 wild-type; exon 21 = exon 21L858R mutations.
Figure 4
Figure 4
rwPFS and OS—TP53 co-mutation vs. TP53 wild-type by Exon21L858R mutation. (A) rwPFS. (B) OS. Unadjusted HR and 95% CI. CI = confidence interval; HR = hazard ratio; OS = overall survival; rwPFS = real-world progression-free survival; TP53mt = TP53 co-mutation; TP53wt = TP53 wild-type; exon 21 = exon 21L858R mutations.
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