(OA02) Circulating Tumor DNA Quantitation for Early Response Assessment of Immune Checkpoint Inhibitors for Metastatic Non-Small Cell Lung Cancer

PURPOSE Immune checkpoint inhibitors (ICIs) are increasingly being used in non–small-cell lung cancer (NSCLC), yet biomarkers predicting their benefit are lacking. We evaluated if on-treatment changes of circulating tumor DNA (ctDNA) from ICI start (t0) to after two cycles (t1) assessed with a commercial panel could identify patients with NSCLC who would benefit from ICI. PATIENTS AND METHODS The molecular ctDNA response was evaluated as a predictor of radiographic tumor response and long-term survival benefit of ICI. To maximize the yield of ctDNA detection, de novo mutation calling was performed. Furthermore, the impact of clonal hematopoiesis (CH)–related variants as a source of biologic noise was investigated. RESULTS After correction for CH-related variants, which were detected in 75 patients (44.9%), ctDNA was detected in 152 of 167 (91.0%) patients. We observed only a fair agreement of the molecular and radiographic response, which was even more impaired by the inclusion of CH-related variants. After exclusion of those, a ≥ 50% molecular response improved progression-free survival (10 v 2 months; hazard ratio [HR], 0.55; 95% CI, 0.39 to 0.77; P = .0011) and overall survival (18.4 v 5.9 months; HR, 0.44; 95% CI, 0.31 to 0.62; P < .0001) compared with patients not achieving this end point. After adjusting for clinical variables, ctDNA response and STK11/ KEAP1 mutations (HR, 2.08; 95% CI, 1.4 to 3.0; P < .001) remained independent predictors for overall survival, irrespective of programmed death ligand-1 expression. A landmark survival analysis at 2 months (n = 129) provided similar results. CONCLUSION On-treatment changes of ctDNA in plasma reveal predictive information for long-term clinical benefit in ICI-treated patients with NSCLC. A broader NSCLC patient coverage through de novo mutation calling and the use of a variant call set excluding CH-related variants improved the classification of molecular responders, but had no significant impact on survival.

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Circulating tumor DNA in early response assessment and monitoring of advanced colorectal cancer treated with a multi-kinase inhibitor

Oncotarget ◽

10.18632/oncotarget.24879 ◽

2018 ◽

Vol 9 (25) ◽

pp. 17756-17769 ◽

Cited By ~ 14

Author(s):

Caroline Vandeputte ◽

Pashalina Kehagias ◽

Hakim El Housni ◽

Lieveke Ameye ◽

Jean-François Laes ◽

...

Keyword(s):

Colorectal Cancer ◽

Advanced Colorectal Cancer ◽

Kinase Inhibitor ◽

Response Assessment ◽

Early Response ◽

Circulating Tumor Dna ◽

Assessment And Monitoring ◽

Early Response Assessment ◽

Tumor Dna

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Predictive and prognostic value of early response assessment using 18FDG-PET in advanced non-small cell lung cancer patients treated with erlotinib

Cancer Chemotherapy and Pharmacology ◽

10.1007/s00280-013-2356-x ◽

2013 ◽

Vol 73 (2) ◽

pp. 299-307 ◽

Cited By ~ 19

Author(s):

Marcello Tiseo ◽

Massimo Ippolito ◽

Maura Scarlattei ◽

Pietro Spadaro ◽

Sebastiano Cosentino ◽

...

Keyword(s):

Lung Cancer ◽

Prognostic Value ◽

Response Assessment ◽

Early Response ◽

Small Cell ◽

Small Cell Lung ◽

Lung Cancer Patients ◽

18Fdg Pet ◽

Early Response Assessment ◽

Predictive And Prognostic Value

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Plasma Biomarkers and Immune Checkpoint Inhibitors in Non-Small Cell Lung Cancer: New Tools for Better Patient Selection?

Cancers ◽

10.3390/cancers11091269 ◽

2019 ◽

Vol 11 (9) ◽

pp. 1269 ◽

Cited By ~ 6

Author(s):

Adrien Costantini ◽

Paul Takam Kamga ◽

Coraline Dumenil ◽

Thierry Chinet ◽

Jean-François Emile ◽

...

Keyword(s):

Lung Cancer ◽

Small Cell Lung Cancer ◽

Cell Lung Cancer ◽

Immune Checkpoint ◽

Immune Checkpoint Inhibitors ◽

Checkpoint Inhibitors ◽

Circulating Tumor Dna ◽

Small Cell ◽

Small Cell Lung ◽

Plasma Biomarkers

Immune checkpoint inhibitors (ICIs) have transformed the treatment landscape for patients with non-small cell lung cancer (NSCLC). Although some patients can experience important response rates and improved survival, many others do not benefit from ICIs developing hyper-progressive disease or immune-related adverse events. This underlines the need to select biomarkers for ICIs use in order to better select patients. There is currently no universally validated robust biomarker for daily use of ICIs. Programmed death-ligand 1 (PD-L1) or tumor mutational burden (TMB) are sometimes used but still have several limitations. Plasma biomarkers are a promising approach in ICI treatment. This review will describe the development of novel plasma biomarkers such as soluble proteins, circulating tumor DNA (ctDNA), blood TMB, and blood microbiome in NSCLC patients treated with ICIs and their potential use in predicting response and toxicity.

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Prognostic value of early response assessment using (18F)FDG-PET in patients with advanced non-small cell lung cancer treated with tyrosine-kinase inhibitors

Journal of Investigative Medicine ◽

10.1136/jim-2017-000433 ◽

2017 ◽

Vol 65 (5) ◽

pp. 935-941 ◽

Cited By ~ 3

Author(s):

Jun Ma ◽

Xiaojing Wu ◽

Jianghong Li ◽

Zhihua Wang ◽

Yi Wang

Keyword(s):

Lung Cancer ◽

Fdg Pet ◽

Prognostic Value ◽

Kinase Inhibitors ◽

Response Assessment ◽

Early Response ◽

Small Cell ◽

Small Cell Lung ◽

Positron Emission ◽

Early Response Assessment

The purpose of this meta-analysis was to determine the prognostic value of early response assessment using (18F)fluorodeoxyglucose (FDG)-positron emission thermography (PET) in patients with advanced non-small cell lung cancer (NSCLC) treated with tyrosine-kinase inhibitors (TKIs). MEDLINE, PubMed, Cochrane, EMBASE, and Google Scholar databases were searched until August 1, 2016 using the keywords non-small cell lung carcinoma, positron-emission tomography, fluorodeoxyglucose, prognosis, disease progression, survival, erlotinib, gefitinib, and afatinib. Inclusion criteria were studies of patients with stage III or IV NSCLC treated with a TKI and had response assessed by FDG-PET. Outcome measures were overall survival (OS) and progression-free survival (PFS). Of the 167 articles identified, 10 studies including 302 patients were included in the analysis. In 8 studies, patients were treated with erlotinib, and in 2 they were treated with gefitinib. The overall analysis revealed that early metabolic response was statistically associated with improved OS (HR=0.54; 95% CI 0.46 to 0.63; p<0.001), and with longer PFS (HR=0.23; 95% CI 0.17 to 0.33; p<0.001). Early response of patients with NSCLC treated with TKIs identified on FDG-PET is associated with improved OS and PFS.

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