Blood-based tumor mutational burden as a predictor of clinical benefit in non-small-cell lung cancer patients treated with atezolizumab

2018 ◽  
Vol 24 (9) ◽  
pp. 1441-1448 ◽  
Author(s):  
David R. Gandara ◽  
Sarah M. Paul ◽  
Marcin Kowanetz ◽  
Erica Schleifman ◽  
Wei Zou ◽  
...  
2020 ◽  
Author(s):  
Sumesh Kachroo ◽  
Changxia Shao ◽  
Kaushal Desai ◽  
Jinghua He ◽  
Fan Jin ◽  
...  

Aim: We evaluated the relationship between clinical and genomic characteristics and tumor mutational burden (TMB) in small cell lung cancer. Materials & methods: In a retrospective analysis of small cell lung cancer patients aged ≥18, we assessed treatment patterns and survival in relation to TMB; the association of clinical and genomic characteristics with TMB was determined by multivariate regression. High TMB (TMB-H) was defined as ≥10 mutations/megabase. Results: Among 186 patients, treatment patterns and overall survival were similar for TMB-H and non-TMB-H patients. TMB was determined for 179 patients, 41.9% of whom were TMB-H. Short variants of LRP1B, FAT3, MLL3, MED12 and NOTCH3 were significantly associated with TMB-H (p ≤ 0.01). Conclusion: Neither treatment patterns nor survival differed by TMB status.


Cancers ◽  
2019 ◽  
Vol 11 (9) ◽  
pp. 1271 ◽  
Author(s):  
Heeke ◽  
Benzaquen ◽  
Long-Mira ◽  
Audelan ◽  
Lespinet ◽  
...  

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.


2017 ◽  
Vol 14 (1) ◽  
pp. 58-77
Author(s):  
Sevgi Gezici ◽  
Mehmet Ozaslan ◽  
Gurler Akpinar ◽  
Murat Kasap ◽  
Maruf Sanli ◽  
...  

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