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Found 1 Presentation For Request "1344P"
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
- Markus Falk (Hamburg, Hamburg, Germany)
Abstract
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.
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.