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

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

doi:10.21037/tlcr-21-754

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

Transl Lung Cancer Res. 2022 Jan;11(1):4-13. doi: 10.21037/tlcr-21-754.

Authors

Julia Roeper^{1

2

3}, Petros Christopoulos^{4

5}, Markus Falk^{3

6}, Lukas C Heukamp^{3

6}, Markus Tiemann^{3

6}, Albrecht Stenzinger⁷, Michael Thomas^{4

5}, Frank Griesinger^{1

2

3}

Affiliations

¹ Department of Internal Medicine-Oncology, Carl v. Ossietzky University of Oldenburg, Pius-Hospital, Oldenburg, Germany.
² Department of Hematology and Oncology, Pius-Hospital, Oldenburg, Germany.
³ Lung Cancer Network NOWEL Organisation, Pius-Hospital, Oldenburg, Germany.
⁴ Thoraxklinik and National Center for Tumor Diseases at Heidelberg University Hospital, Heidelberg, Germany.
⁵ Translational Lung Research Center Heidelberg (TLRC-H), member of the German Center for Lung Research (DZL), University Hospital, Heidelberg, Germany.
⁶ Hematopathology Hamburg, Hamburg, Germany.
⁷ Department of General Pathology and Pathological Anatomy, University Hospital, Heidelberg, Germany.

Abstract

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 objective response rate (ORR), progression free survival (PFS) and overall survival (OS) with 1st and 2nd generation tyrosine kinase inhibitors (TKI). However, a negative predictive impact has not been shown for the 3rd generation TKI Osimertinib. Therefore, we investigated the impact of TP53 mt+ in EGFR mt+ NSCLC carrying a T790M resistance mutation and treated in 2nd/further lines with Osimertinib.

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.

Keywords: EGFR; Non-small cell lung cancer (NSCLC); Osimertinib; TP53 co-mutation; metastatic.