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In-house implementation of tumor mutational burden testing to predict durable clinical benefit in non-small cell lung cancer and melanoma patients

Tumor mutational burden (TMB) has emerged as an important potential biomarker for prediction of response to immune-checkpoint inhibitors (ICIs), notably in non-small cell lung cancer (NSCLC). However, its in-house assessment in routine clinical practice is currently challenging and validation is urg...

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Hauptverfasser: Heeke, Simon (VerfasserIn) , Stenzinger, Albrecht (VerfasserIn)
Dokumenttyp: Article (Journal)
Sprache:Englisch
Veröffentlicht: 29 August 2019
In: Cancers
Year: 2019, Jahrgang: 11, Heft: 9
ISSN:2072-6694
DOI:10.3390/cancers11091271
Online-Zugang:Verlag, Volltext: https://doi.org/10.3390/cancers11091271
Verlag: https://www.mdpi.com/2072-6694/11/9/1271
Volltext
Verfasserangaben:Simon Heeke, Jonathan Benzaquen, Elodie Long-Mira, Benoit Audelan, Virginie Lespinet, Olivier Bordone, Salomé Lalvée, Katia Zahaf, Michel Poudenx, Olivier Humbert, Henri Montaudié, Pierre-Michel Dugourd, Madleen Chassang, Thierry Passeron, Hervé Delingette, Charles-Hugo Marquette, Véronique Hofman, Albrecht Stenzinger, Marius Ilié and Paul Hofman
Beschreibung
Zusammenfassung:Tumor mutational burden (TMB) has emerged as an important potential biomarker for prediction of response to immune-checkpoint inhibitors (ICIs), notably in non-small cell lung cancer (NSCLC). However, its in-house assessment in routine clinical practice is currently challenging and validation is urgently needed. We have analyzed sixty NSCLC and thirty-six melanoma patients with ICI treatment, using the FoundationOne test (FO) in addition to in-house testing using the Oncomine TML (OTML) panel and evaluated the durable clinical benefit (DCB), defined by >6 months without progressive disease. Comparison of TMB values obtained by both tests demonstrated a high correlation in NSCLC (R2 = 0.73) and melanoma (R2 = 0.94). The association of TMB with DCB was comparable between OTML (area-under the curve (AUC) = 0.67) and FO (AUC = 0.71) in NSCLC. Median TMB was higher in the DCB cohort and progression-free survival (PFS) was prolonged in patients with high TMB (OTML HR = 0.35; FO HR = 0.45). In contrast, we detected no differences in PFS and median TMB in our melanoma cohort. Combining TMB with PD-L1 and CD8-expression by immunohistochemistry improved the predictive value. We conclude that in our cohort both approaches are equally able to assess TMB and to predict DCB in NSCLC.
Beschreibung:Gesehen am 05.11.2019
Beschreibung:Online Resource
ISSN:2072-6694
DOI:10.3390/cancers11091271

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