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E-Poster Display

1344P - The impact of TP53 mutations on EGFR mt+ NSCLC IV patients treated with 3rd generation TKI on second-line or further line therapy: Real world data from the German CRISP registry

Date

17 Sep 2020

Session

E-Poster Display

Topics

Tumour Site

Non-Small Cell Lung Cancer

Presenters

Markus Falk

Citation

Annals of Oncology (2020) 31 (suppl_4): S754-S840. 10.1016/annonc/annonc283

Authors

M. Falk1, J. Roeper2, L. Heukamp3, M. Tiemann4, A. Stenzinger5, M. Thomas6, P. Christopoulos6, F. Griesinger7

Author affiliations

  • 1 Molecular Pathology Department, Hematopathology Hamburg, 22547 - Hamburg/DE
  • 2 Department Of Internal Medicine-oncology, Pius Hospital Oldenburg, University of Oldenburg, 26121 - Oldenburg/DE
  • 3 Nowel, Lung Cancer Network, 26121 - Oldenburg/DE
  • 4 Hematopathology Hamburg, Hematopathology Hamburg, 22547 - Hamburg/DE
  • 5 Institute Of Pathology, Heidelberg University Hospital, 69120 - Heidelberg/DE
  • 6 Thoracic Oncology/internal Medicine, Thoraxklinik Heidelberg, 69126 - Heidelberg/DE
  • 7 Hematology And Oncology, Pius Hospital, University of Oldenburg, Oldenburg/DE

Resources

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Abstract 1344P

Background

TP53 co-mutations are frequent in EGFR mt+ NSCLC and have a strong negative impact on all clinical endpoints in 1st and 2nd generation TKI therapy. However, it is unclear, whether TP53 mutations also have an impact on the effectiveness of 3rd generation TKI. Therefore, we retrospectively analyzed the impact of TP53 co-mutations on PFS and OS in a cohort of EGFR mt+ NSCLC IV patients (UICC 7/8) who developed T790M resistance to 1st and 2nd generation TKI and were treated with 3rd generation TKI in 2nd or further line.

Methods

78 EGFR mt+ NSCLC IV patients tested for TP53 co-mutations and showing a T790M resistance mechanism against 1st or 2nd generation TKI were treated with 3rd generation TKI (Osimertinib) in 2nd or further lines. The endpoints PFS and OS were investigated in the TP53mt+ vs. TP53WT groups for only 2nd line (25 TP53 mt+ vs. 28 TP WT) and for the complete population (2nd and further line).

Results

Baseline characteristics of the 78 EGFR mt+ NSCLC IV patients: median age was 64 years (28-92 years), 65.4% were female (n=51/78), 70.5% were never/light smoker (n=55/78) and 91% had an ECOG of 0 or 1 (n=71/78). 33/78 (42.3%) had a TP53 mutation, 45/78 (57.7%) were TP53 WT. Median PFS of 3rd generation TKI in 2nd line was 8 (n=25) vs. 11 months (n=28) for TP53 mt+ vs. WT (HR 0.492; p<0.037). Median PFS of 3rd generation TKI in 2nd and further lines was 9 (n=33) vs. 13 (n=45) months for TP53 mt+ vs. WT (HR 0.461; p<0.005). Median OS of 3rd generation TKI in 2nd line therapy was 24 vs. 41 months, for TP53 mt+ vs. WT (HR 0.514; p<0.126). Median OS of 3rd generation TKI in 2nd and further lines was 14 vs. 26 months for TP53mt+ vs. WT (HR 0.483; p<0.029).

Conclusions

TP53 co-mutations have a negative impact on PFS and OS in EGFR mt+ NSCLC IV patients treated with 3rd generation TKI (Osimertinib) in 2nd line and 2nd/further lines. Thus, p53 is a negative predictor in EGFR mt+ NSCLC patients treated with Osimertinib. TP53 might be an important target to drug in EGFR mt+ NSCLC in combination with Osimertinib.

Clinical trial identification

Editorial acknowledgement

Legal entity responsible for the study

Carl-v-Ossietzky University Oldenburg.

Funding

Has not received any funding.

Disclosure

M. Falk: Honoraria (self), Advisory/Consultancy: Boehringer Ingelheim; Advisory/Consultancy: Pfizer; Honoraria (self): Roche; Honoraria (self): AstraZeneca. J. Roeper: Honoraria (self): Boehringer Ingelheim; Honoraria (self): AstraZeneca; Honoraria (self): Roche. L. Heukamp: Honoraria (self), Advisory/Consultancy: AstraZeneca; Honoraria (self), Advisory/Consultancy: Boehringer Ingelheim; Honoraria (self), Advisory/Consultancy: Novartis; Honoraria (self), Advisory/Consultancy: Pfizer; Honoraria (self), Advisory/Consultancy: Roche; Honoraria (self), Advisory/Consultancy: MSD; Honoraria (self), Advisory/Consultancy: BMS; Honoraria (self), Advisory/Consultancy: Siemens. M. Tiemann: Honoraria (self), Advisory/Consultancy, Research grant/Funding (institution): Novartis; Honoraria (self), Advisory/Consultancy: Boehringer Ingelheim; Honoraria (self), Advisory/Consultancy: BMS; Honoraria (self), Advisory/Consultancy: MSD; Honoraria (self), Advisory/Consultancy: Roche; Honoraria (self), Advisory/Consultancy: AstraZeneca. M. Thomas: Advisory/Consultancy, Travel/Accommodation/Expenses: Novartis; Advisory/Consultancy, Research grant/Funding (institution), Travel/Accommodation/Expenses: BMS; Advisory/Consultancy, Speaker Bureau/Expert testimony, Travel/Accommodation/Expenses: MSD; Advisory/Consultancy, Speaker Bureau/Expert testimony: Lilly; Advisory/Consultancy, Research grant/Funding (institution): Roche; Advisory/Consultancy, Research grant/Funding (institution): Celgene; Advisory/Consultancy, Speaker Bureau/Expert testimony: Takeda; Advisory/Consultancy: AbbVie; Advisory/Consultancy, Travel/Accommodation/Expenses: Boehringer Ingelheim; Advisory/Consultancy: AstraZeneca. P. Christopoulos: Honoraria (self), Speaker Bureau/Expert testimony, Research grant/Funding (institution): AstraZeneca; Honoraria (self), Advisory/Consultancy, Research grant/Funding (institution): Roche; Honoraria (self), Advisory/Consultancy, Research grant/Funding (institution): Novartis; Honoraria (self), Advisory/Consultancy, Research grant/Funding (institution): Takeda; Honoraria (self), Advisory/Consultancy: Boehriger Ingelheim; Honoraria (self), Advisory/Consultancy: Chugai; Honoraria (self), Advisory/Consultancy: Pfizer. F. Griesinger: Honoraria (self), Advisory/Consultancy, Speaker Bureau/Expert testimony, Research grant/Funding (institution), Travel/Accommodation/Expenses: AstraZeneca; Honoraria (self), Advisory/Consultancy, Speaker Bureau/Expert testimony, Research grant/Funding (institution), Travel/Accommodation/Expenses: Boehringer Ingelheim; Honoraria (self), Advisory/Consultancy, Speaker Bureau/Expert testimony, Research grant/Funding (institution), Travel/Accommodation/Expenses: BMS; Honoraria (self), Advisory/Consultancy, Speaker Bureau/Expert testimony, Research grant/Funding (institution), Travel/Accommodation/Expenses: MSD; Honoraria (self), Advisory/Consultancy, Speaker Bureau/Expert testimony, Research grant/Funding (institution), Travel/Accommodation/Expenses: Novartis; Honoraria (self), Advisory/Consultancy, Speaker Bureau/Expert testimony, Research grant/Funding (institution), Travel/Accommodation/Expenses: Pfizer; Honoraria (self), Advisory/Consultancy, Speaker Bureau/Expert testimony, Research grant/Funding (institution), Travel/Accommodation/Expenses: Takeda; Honoraria (self), Advisory/Consultancy, Speaker Bureau/Expert testimony, Research grant/Funding (institution), Travel/Accommodation/Expenses: Roche; Honoraria (self), Advisory/Consultancy, Speaker Bureau/Expert testimony, Research grant/Funding (institution), Travel/Accommodation/Expenses: Celgene; Honoraria (self), Advisory/Consultancy, Speaker Bureau/Expert testimony, Travel/Accommodation/Expenses: AbbVie; Honoraria (self), Advisory/Consultancy, Speaker Bureau/Expert testimony, Research grant/Funding (institution), Travel/Accommodation/Expenses: Lilly; Honoraria (self), Advisory/Consultancy, Speaker Bureau/Expert testimony, Research grant/Funding (institution), Travel/Accommodation/Expenses: Siemens. All other authors have declared no conflicts of interest.

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