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Outcome of first-line treatment with pembrolizumab according to KRAS/TP53 mutational status for non-squamous PD-L1 high (≥50%) NSCLC in the German National Network Genomic Medicine Lung Cancer (nNGM)

Philip Bischoff
Martin Reck
Tobias Overbeck
Petros Christopoulos
Achim Rittmeyer
Heike Lüders
Jens Kollmeier
Jonas Kulhavy
Marcel Kemper
Niels Reinmuth
Julia Röper
Melanie Janning
Linna Sommer
Lukas Aguinarte
Myriam Koch
Marcel Wiesweg
Claas Wesseler
Cornelius F. Waller
Diego Kauffmann-Guerrero
Albrecht Stenzinger
Susann Stephan-Falkenau
Marcel Trautmann
Silke Lassmann
Markus Tiemann
Frederick Klauschen
Martin Sebastian
Frank Griesinger
Jürgen Wolf
Sonja Loges
Nikolaj Frost

December 13, 2023

PD-L1 expression currently represents the only validated predictive biomarker for immune checkpoint inhibition in metastatic non-small cell lung cancer (NSCLC) in the clinical routine, but has limited value to distinguish responses. Assessment of KRAS and TP53 mutations (mut) as surrogate for an immunosupportive tumor microenvironment (TME) might help to close this gap.

Patients and Methods
696 consecutive patients with PD-L1 high (≥50%), non-squamous NSCLC, having received molecular testing within the German National Network Genomic Medicine Lung Cancer between 2017 and 2020, with ECOG-PS ≤1 and pembrolizumab as first-line palliative treatment were included into this retrospective cohort analysis. Treatment efficacy and outcome according to KRAS/TP53 status were correlated with TME composition and gene expression analysis of the TCGA lung adenocarcinoma cohort.