TP53 co-mutations as an independent prognostic factor in 2nd and further line therapy- EGFR mutated non-small cell lung cancer IV patients treated with osimertinib

TP53 共突变是二线及后续治疗中独立的预后因素 - 接受奥希替尼治疗的 EGFR 突变非小细胞肺癌 IV 患者

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作者:Julia Roeper, Petros Christopoulos, Markus Falk, Lukas C Heukamp, Markus Tiemann, Albrecht Stenzinger, Michael Thomas, Frank Griesinger

Background

The negative prognostic and predictive value of TP53 co-mutations (TP53 mt+) in EGFR mutated (EGFR mt+) non-small cell lung cancer (NSCLC) is increasingly being acknowledged. Data consistently show that TP53 mt+ impact negatively on 1st line

Conclusions

TP53 mt+ have a negative impact on PFS and OS in a group of patients carrying a sensitizing EGFR mt+ and a T790M resistance mutation treated with Osimertinib. These data, together with the data for 1st/2nd generation TKI in 1st line treatment call for additional therapeutic and management concepts for this subgroup of patients.

Methods

A total of 77 EGFR mt+ NSCLC IV patients carrying a T790M resistance mutation from two institutions were analyzed for TP53 mt+. Clinical data including sex, age, presence of CNS metastases, etc., as well as types of EGFR and TP53 mt+ were captured. PFS and OS were calculated from the start of Osimertinib.

Results

TP53 mt+ were found in 32/77 patients (42%). TP53 mt+ was a statistically significant independent negative predictive factor for PFS and OS. PFS for TP53 mt+ patients were 9 months vs. 14 months for patients with TP53 wild-type (TP53WT) (P<0.008). OS for TP53 mt+ patients was 16 months vs. 24 months patients with TP53WT (P<0.025). Conclusions: TP53 mt+ have a negative impact on PFS and OS in a group of patients carrying a sensitizing EGFR mt+ and a T790M resistance mutation treated with Osimertinib. These data, together with the data for 1st/2nd generation TKI in 1st line treatment call for additional therapeutic and management concepts for this subgroup of patients.

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