Tumour mutational burden and survival with molecularly matched therapy

The impact of tumour mutational burden (TMB) on outcome with molecularly matched therapy is unknown. Higher TMB could predict resistance to molecularly matched therapy through co-occurring driver mutations. One hundred and four patients with advanced cancers underwent molecular profiling in the DKTK...

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Published in:European journal of cancer (1990) 2023-09, Vol.190, p.112925-112925, Article 112925
Main Authors: de Bortoli, Till, Benary, Manuela, Horak, Peter, Lamping, Mario, Stintzing, Sebastian, Tinhofer, Ingeborg, Leyvraz, Serge, Schäfer, Reinhold, Klauschen, Frederick, Keller, Ulrich, Stenzinger, Albrecht, Fröhling, Stefan, Kurzrock, Razelle, Keilholz, Ulrich, Rieke, Damian T, Jelas, Ivan
Format: Article
Language:English
Subjects:
Biomarkers, Tumor - genetics
Biomarkers, Tumor - metabolism
Humans
Immunotherapy - methods
Mutation
Neoplasms - drug therapy
Neoplasms - genetics
Precision Medicine
Progression-Free Survival
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Summary:The impact of tumour mutational burden (TMB) on outcome with molecularly matched therapy is unknown. Higher TMB could predict resistance to molecularly matched therapy through co-occurring driver mutations. One hundred and four patients with advanced cancers underwent molecular profiling in the DKTK-MASTER program. Fifty-five patients received systemic therapy excluding immunotherapy. Patients with molecularly matched (n = 35) or non-molecularly informed therapy (n = 20) were analysed for TMB and survival. Results were validated in an independent cohort of patients receiving molecularly matched (n = 68) or non-molecularly informed therapy (n = 40). Co-occurring driver mutations and TMB were analysed in the exploratory cohort and The Cancer Genome Atlas (TCGA) datasets. Patients were stratified by the median TMB of 1.67 mutations per Megabase (mut/Mb) of 35 patients receiving molecularly matched therapy into TMB-high or TMB-low groups. Median overall survival (4 months [95% CI, 3.3-7.6] versus 12.8 months [95% CI, 10-not reached], p 
ISSN:0959-8049
1879-0852
DOI:10.1016/j.ejca.2023.05.013