Blood-based tumor mutational burden from circulating tumor DNA (ctDNA) across advanced solid malignancies using a commercially available liquid biopsy assay.

Authors

null

Leylah Drusbosky

Guardant Health, Inc., Redwood City, CA

Leylah Drusbosky , Mehmet Asim Bilen , Georges Azzi , Pedro C. Barata , Patrick M Boland , Alan Haruo Bryce , Young Kwang Chae , Jeremy Meyer Force , Martin Gutierrez , Pashtoon Murtaza Kasi , Hiba I. Dada , Caroline Weipert , Chuck Hensel , Lesli A. Kiedrowski , Che-Yu Lee , Martina Lefterova , David R. Gandara

Organizations

Guardant Health, Inc., Redwood City, CA, Department of Hematology and Medical Oncology, Emory University School of Medicine, Atlanta, GA, Holy Cross Medical Group, Michael and Dianne Bienes Comprehensive Cancer Center, Fort Lauderdale, FL, Tulane Cancer Center, New Orleans, LA, Rutgers Cancer Institute of New Jersey, New Brunswick, NJ, Mayo Clinic, Phoenix, AZ, Northwestern University Feinberg School of Medicine, Chicago, IL, Duke University Medical Center, Duke Cancer Institute, Durham, NC, John Theurer Cancer Center at Hackensack University Medical Center, Hackensack, NJ, University Of Iowa, Iowa City, IA, University of California Davis Comprehensive Cancer Center, Sacramento, CA

Research Funding

No funding received
None

Background: Pembrolizumab was recently FDA approved across solid tumors for TMB scores ≥ 10mut/Mb as assessed by next-generation sequencing (NGS) of tissue (tTMB). A prior study of advanced cancer patients treated with immunotherapy found that higher somatic TMB, as defined by the 80th percentile in each histology, was associated with better overall survival. Previously, bTMB assessed by ctDNA from patients with newly diagnosed advanced NSCLC at a score of 16 mut/MB correlated with a tTMB score of 10 mut/MB. TMB levels vary by cancer type, line of treatment, and therapy received; the distribution of bTMB scores across solid tumor types has not been well characterized. Here we report the distribution of bTMB scores in patients with advanced malignancies. Methods: We queried 5,610 samples from patients with different cancer types undergoing clinical cell-free DNA testing (Guardant360; Redwood City, CA) and assessed bTMB scores from October 2020 - January 2021. bTMB score was derived via a previously described computational algorithm examining the total number of synonymous and non-synonymous SNVs and indels across a 1.0MB genomic footprint. We assessed the success rate of bTMB evaluation, overlap with microsatellite instability (MSI) status, and defined the distribution of bTMB levels across indications in this dataset. Results: bTMB score was successfully assessed in 4,275/5,610 (76.3%) samples (Table). The majority of samples (58%) were tested at disease progression as compared to initial diagnosis (42%). The median turnaround time from sample receipt to clinical reporting was 11 days and decreased to 9 days over the course of the study. For the majority of cancer types the 80th percentile TMB was ≥ 16 mut/MB tissue equivalency. Conclusions: Our analysis demonstrates the feasibility of measuring bTMB using a commercially available liquid biopsy assay. bTMB scores trended higher than tTMB previously reported in these cancer types, reflecting the ability of ctDNA to better capture tumor heterogeneity. cfDNA may allow for exploration of bTMB evolution throughout treatment. TMB should be interpreted in the context of disease, treatment, and method; these data establish a pan-cancer benchmark for bTMB which will serve as a resource for further studies.

      Tumor TypeMale %Mean agectDNA tested at diagnosisctDNA tested at disease progression80th %ile (mut/MB)MSI-H and TMB ≥ 80th %ilebTMB Success Rate
Melanoma52%62.947%53%23.80%74%
Colorectal56%61.530%70%20.116%84%
Lung48%69.358%42%20.23%77%
Bladder83%70.946%54%20.113%82%
Head & Neck67%65.638%51%17.47%66%
GYN0%70.032%68%17.262%70%
Breast1%61.722%78%15.37%79%
Prostate100%72.616%84%13.418%80%
Pancreatic49%67.148%52%11.46%72%

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Abstract Details

Meeting

2021 ASCO Annual Meeting

Session Type

Poster Session

Session Title

Developmental Therapeutics—Molecularly Targeted Agents and Tumor Biology

Track

Developmental Therapeutics—Molecularly Targeted Agents and Tumor Biology

Sub Track

Circulating Biomarkers

Citation

J Clin Oncol 39, 2021 (suppl 15; abstr 3040)

DOI

10.1200/JCO.2021.39.15_suppl.3040

Abstract #

3040

Poster Bd #

Online Only

Abstract Disclosures

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