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Association details:
| Biomarker: | EGFR mutation + TP53 mutation + BRCA1 mutation |
|---|---|
| Cancer: | Non Small Cell Lung Cancer |
| Drug Class: | EGFR inhibitor |
| Direction: | Resistant |
Evidence:
Source:
Title:
Co-occurring Alterations in Multiple Tumor Suppressor Genes are Associated with Worse Outcomes in Patients with EGFR-mutant Lung Cancer
Published date:
10/05/2023
Excerpt:
Patients with EGFR-mutant NSCLC treated with EGFR-TKIs who had tumor genomic profiling were included. Alterations in TP53 and five additional TSGs (RB1, NF1, ARID1A, BRCA1 and PTEN) were used to stratify the cohort into three subgroups: patients with tumors harboring a TP53 mutation plus a mutation in ≥1 additional TSG (TP53mut/TSGmut), a TP53 mutation without additional TSG mutations (TP53mut/TSGwt), and TP53wt....Specifically, in the Yale cohort for patients receiving first-line TKI, those with TP53mut/TSGmut tumors had shorter PFS and OS than TP53mut/TSGwt (PFS: HR 2.03, CI 1.12 – 3.69, P<0.01, OS: HR 1.58, CI 0.82 – 3.04, P=0.12) or TP53wt cases (PFS: HR 2.4, CI 1.28 – 4.47, P<0.001, OS: HR 2.54, CI 1.21 – 5.34, P<0.005).
DOI:
https://doi.org/10.1016/j.jtho.2023.10.001
Source:
Title:
Co-occurring Alterations in Multiple Tumor Suppressor Genes are Associated with Worse Outcomes in Patients with EGFR-mutant Lung Cancer
Published date:
01/28/2023
Excerpt:
Patients with EGFR-mutant NSCLC treated with EGFR-TKIs at the Yale Cancer Center who had tumor genomic profiling were included. Alterations in TP53 and five additional TSGs (RB1, NF1, ARID1A, BRCA1 and PTEN)…patients with TP53mut/TSGmut tumors had significantly worse PFS (Figure 1) and OS on EGFR-TKI than TP53mut/TSGwt (mPFS 8.0 vs 10.6 months, p=0.006; mOS 30.0 vs 33.3 months, p=0.12) or TP53wt cases (mPFS 8.0 vs 12.6 months, p<0.0001; mOS 30.0 vs 48.8 months, p=0.001)....The inferior outcomes in patients with EGFR-mutant NSCLC with tumors harboring a co-occurring TP53 mutation may be due to additional TSG alterations rather than TP53 mutational status alone.
