; Kluck, Klaus ; Kirchner, Martina ; Lüders, Heike ; Roeper, Julia ; Falkenstern-Ge, Roger-Fei ; Szewczyk, Marlen ; Sticht, Florian ; Saalfeld, Felix C.
; Wesseler, Claas
; Hackanson, Björn ; Dintner, Sebastian ; Faehling, Martin ; Kuon, Jonas ; Janning, Melanie ; Kauffmann-Guerrero, Diego ; Kazdal, Daniel ; Kurz, Sylke ; Eichhorn, Florian ; Bozorgmehr, Farastuk ; Shah, Rajiv
; Tufman, Amanda ; Wermke, Martin ; Loges, Sonja ; Brueckl, Wolfgang M. ; Schulz, Christian ; Misch, Daniel ; Frost, Nikolaj
; Kollmeier, Jens
; Reck, Martin ; Griesinger, Frank ; Grohé, Christian ; Hong, Jin-Liern ; Lin, Huamao M. ; Budczies, Jan
; Stenzinger, Albrecht ; Thomas, Michael | Dokumentenart: | Artikel | ||||
|---|---|---|---|---|---|
| Titel eines Journals oder einer Zeitschrift: | European Journal of Cancer | ||||
| Verlag: | Elsevier | ||||
| Ort der Veröffentlichung: | OXFORD | ||||
| Band: | 170 | ||||
| Seitenbereich: | S. 106-118 | ||||
| Datum: | 2022 | ||||
| Institutionen: | Medizin > Lehrstuhl für Innere Medizin II | ||||
| Identifikationsnummer: |
| ||||
| Stichwörter / 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 | ||||
| Dewey-Dezimal-Klassifikation: | 600 Technik, Medizin, angewandte Wissenschaften > 610 Medizin | ||||
| Status: | Veröffentlicht | ||||
| Begutachtet: | Ja, diese Version wurde begutachtet | ||||
| An der Universität Regensburg entstanden: | Ja | ||||
| Dokumenten-ID: | 57760 |
Zusammenfassung
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: ...

Zusammenfassung
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.
Metadaten zuletzt geändert: 29 Feb 2024 13:02
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