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
Translational Lung Cancer Research [S.l.] : [s.n.], 2012 11(2022), 1, Seite 4-16 Online-Ressource
von Nikolaj Frost ; Julia Roeper ; Janna-Lisa Velthaus ; Matthias Raspe ; Elisabeth Olive ; Alexander Schmittel ; Bernd Schmidt ; David Wasilewski ; Julia Onken ; Heike Lüders ; Martin Witzenrath ; Carolin Senger ; Dirk Böhmer ; Sonja Loges ; Frank Griesinger ; Dominik Paul Modest ; Christian Grohé
von Julia Roeper ; Nikolaj Frost ; Martin Wermke ; Felix Saalfeld ; Daniel Heudobler ; Tobias Pukrop ; Melanie Janning ; Jonas Kuon ; Rieke Kempfer ; Lucia Nogová ; Petros Christopoulos ; Frank Griesinger
von Petros Christopoulos ; Klaus Kluck ; Martina Kirchner ; Heike Lüders ; Julia Roeper ; Roger-Fei Falkenstern-Ge ; Marlen Szewczyk ; Florian Sticht ; Felix C. Saalfeld ; Claas Wesseler ; Björn Hackanson ; Sebastian Dintner ; Martin Faehling ; Jonas Kuon ; Melanie Janning ; Diego Kauffmann-Guerrero ; Daniel Kazdal ; Sylke Kurz ; Florian Eichhorn ; Farastuk Bozorgmehr ; Rajiv Shah ; Amanda Tufman ; Martin Wermke ; Sonja Loges ; Wolfgang M. Brueckl ; Christian Schulz ; Daniel Misch ; Nikolaj Frost ; Jens Kollmeier ; Martin Reck ; Frank Griesinger ; Christian Grohé ; Jin-Liern Hong ; Huamao M. Lin ; Jan Budczies ; Albrecht Stenzinger ; Michael Thomas
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, ≈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.
European journal of cancer Amsterdam [u.a.] : Elsevier, 1992 170(2022) vom: Juli, Seite 106-118
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