Christopoulos, Petros and Kluck, Klaus and Kirchner, Martina and Lueders, Heike and Roeper, Julia and Falkenstern-Ge, Roger-Fei and Szewczyk, Marlen and Sticht, Florian and Saalfeld, Felix C. and Wesseler, Claas and Hackanson, Bjoern and Dintner, Sebastian and Faehling, Martin and Kuon, Jonas and Janning, Melanie and Kauffmann-Guerrero, Diego and Kazdal, Daniel and Kurz, Sylke and Eichhorn, Florian and Bozorgmehr, Farastuk and Shah, Rajiv and Tufman, Amanda and Wermke, Martin and Loges, Sonja and Brueckl, Wolfgang M. and Schulz, Christian and Misch, Daniel and Frost, Nikolaj and Kollmeier, Jens and Reck, Martin and Griesinger, Frank and Grohe, Christian and Hong, Jin-Liern and Lin, Huamao M. and Budczies, Jan and Stenzinger, Albrecht and Thomas, Michael (2022) The impact of TP53 co-mutations and immunologic microenvironment on outcome of lung cancer with EGFR exon 20 insertions. EUROPEAN JOURNAL OF CANCER, 170. pp. 106-118. ISSN 0959-8049, 1879-0852
Full text not available from this repository. (Request a copy)Abstract
Background: EGFR exon20 insertions (ex20ins) are targeted by novel compounds in non-small-cell lung cancer (NSCLC). However, data about outcome under conventional therapies and the influence of molecular features are scarce. Patients and methods: We retrospectively analysed 118 patients with evaluation of radiologic response based on RECIST v1.1. TP53 status was available for 88 cases. Results: Platinum doublets and chemoimmunotherapy showed similar response rates (20-25%), disease control rates (80%) and median progression-free survival (mPFS, asymptotic to 7 months), which were longer compared to monochemotherapy (9%, 59%, 4.1 months), EGFR inhibitors (0%, 46%, 3.0) and PD-(L)1 inhibitors (0%, 30%, 2.1; p < 0.05). Overall survival (OS) was not dependent on the choice of first-line treatment, but related to more lines of systemic therapy (p < 0.05). TP53 mutations and brain metastases were associated with shorter PFS under platinum doublets and EGFR inhibitors (HR 3.3-6.1, p < 0.01), and shorter OS for patients receiving both treatments (p < 0.05). More tumour CD8(+) and less Th1 cells were associated with longer OS independent of brain and TP53 status (p < 0.01). No difference in outcome was noted according to the ex20ins site and use of pemetrexed (vs. other cytotoxics) or bevacizumab. Long-lasting responses (>1 year) occasionally occurred under EGFR inhibitors for both 'near-' and 'far-loop' variants. Conclusions: Platinum doublets and chemoimmunotherapy have the highest activity with ORR of 20-25% and mPFS of approximately 7 months, regardless of the cytotoxic partner, while PD-(L)1 inhibitors show limited efficacy. TP53 mutations, brain metastases and a lower tumour CD8/Th1-cell ratio are independently associated with shorter survival. (C) 2022 Elsevier Ltd. All rights reserved.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | PRETREATED PATIENTS; MOBOCERTINIB; NSCLC; SURVIVAL; DIAGNOSIS; EGFR(+) NSCLC; EGFR exon 20; TP53 mutation; Brain metastases; Immunologic tumour microenvironment; CD8 cells; Th1 cells; Treatment failure; Overall survival |
| Subjects: | 600 Technology > 610 Medical sciences Medicine |
| Divisions: | Medicine > Lehrstuhl für Innere Medizin II |
| Depositing User: | Dr. Gernot Deinzer |
| Date Deposited: | 12 Dec 2023 11:20 |
| Last Modified: | 12 Dec 2023 11:20 |
| URI: | https://pred.uni-regensburg.de/id/eprint/58758 |
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