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Associations of tissue tumor mutational burden and mutational status with clinical outcomes in KEYNOTE-042: pembrolizumab versus chemotherapy for advanced PD-L1-positive NSCLC

Date
2023
Author
Wu, Y. -l.
Mok, T. S. K.
Lopes, G.
Cho, B. C.
Kowalski, D. M.
Kasahara, K.
de Castro Jr, G.
TURNA, ZEYNEP HANDE
Cristescu, R.
Aurora-Garg, D.
Loboda, A.
Lunceford, J.
Kobie, J.
Ayers, M.
Pietanza, M. C.
Piperdi, B.
Herbst, R. S.
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Abstract
Background: We evaluated whether tissue tumor mutational burden (tTMB) and STK11, KEAP1, and KRAS mutations have clinical utility as biomarkers for pembrolizumab monotherapy versus platinum-based chemotherapy in patients with programmed death ligand 1 (PD-L1)-positive (tumor proportion score >1%) advanced/metastatic non-small-cell lung cancer (NSCLC) without EGFR/ALK alterations in the phase III KEYNOTE-042 trial. Patients and methods: This retrospective exploratory analysis assessed prevalence of tTMB and STK11, KEAP1, and KRAS mutations determined by whole-exome sequencing of tumor tissue and matched normal DNA and their associations with outcomes in KEYNOTE-042. Clinical utility of tTMB was assessed using a prespecified cut point of 175 mutations/exome. Results: Of 793 patients, 345 (43.5%) had tTMB >175 mutations/exome and 448 (56.5%) had tTMB 0.05). tTMB >175 mutations/exome was associated with improved outcomes for pembrolizumab versus chemotherapy, whereas tTMB 175 mutations/exome is a potential predictive biomarker for pembrolizumab monotherapy for advanced/metastatic PD-L1 tumor proportion score >1% NSCLC. Pembrolizumab is a standard first-line treatment in this setting regardless of STK11, KEAP1, or KRAS mutation status.
URI
http://hdl.handle.net/20.500.12627/189212
https://doi.org/10.1016/j.annonc.2023.01.011
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Creative Commons Lisansı

İstanbul Üniversitesi Akademik Arşiv Sistemi (ilgili içerikte aksi belirtilmediği sürece) Creative Commons Alıntı-GayriTicari-Türetilemez 4.0 Uluslararası Lisansı ile lisanslanmıştır.

DSpace software copyright © 2002-2016  DuraSpace
Contact Us | Send Feedback
Theme by 
Atmire NV