Abstract 3662
Background
Liquid biopsies have potential clinical utility as dynamic biomarkers for treatment response. We analyzed serial changes in whole-genome (WG) cfDNA to identify patients with disease progression prior to routine imaging.
Methods
We prospectively collected clinical data and blood from 93 advanced cancer patients (40 lung, 25 breast, 28 other). Blood was collected prior to initiation of a new treatment and at one or two additional timepoints (median 21 and 42 days). We isolated plasma cfDNA and prepared sequencing libraries for each patient’s series for either WG sequencing or WG bisulfite sequencing. We quantified changes in the fraction of tumor-derived cfDNA over the initial course of treatment to predict progression vs. no progression. Treatment response at first follow-up imaging (FUI) was determined by RECIST 1.1 and clinical assessment. Study endpoints were agreement with FUI and progression-free survival (PFS) by cfDNA prediction.
Results
Patients were treated with chemo- (34), immuno- (33), targeted- (16), or endocrine therapy (10). Patients with predicted progression by cfDNA (16), indicated by an increase in tumor fraction in either post-treatment blood sample, had shorter PFS (median 64 days) compared to patients without an increase (77; median 263 days), with a hazard ratio of 8.0 (95% confidence interval 4.1-15.6, log-rank P = 8x10-13). For cases where progression was correctly predicted using cfDNA (14), blood collection preceded imaging by a median of 40 days. Positive predictive value was 88% for disease progression and negative predictive value was 84%. Sensitivity for the assay was 54% and specificity was 97%. These findings were consistent in the subset of patients on immunotherapy (sensitivity 71%, specificity 100%, log-rank P = 5x10-12).
Conclusions
Our results show the ability to detect early disease progression with high specificity using liquid biopsy prior to first imaging. These findings were consistent across a variety of tumor histologies and types of treatment. This technology may enable early switching from ineffective therapy to a potentially effective alternative, increasing the value proposition of all delivered treatment.
Clinical trial identification
Editorial acknowledgement
Legal entity responsible for the study
The authors.
Funding
Lexent Bio, Inc.
Disclosure
A.A. Davis: Travel / Accommodation / Expenses: Menarini Silicon Biosystems. W. Iams: Travel / Accommodation / Expenses, Clinical Trial Visit: EMD Serono. N. Peterman: Shareholder / Stockholder / Stock options, Full / Part-time employment: Lexent Bio, Inc. A. Robertson: Shareholder / Stockholder / Stock options, Full / Part-time employment: Lexent Bio, Inc.; Full / Part-time employment, 2016-2017: Color Genomics; Shareholder / Stockholder / Stock options, 2015-2018: Counsyl. A. Shah: Full / Part-time employment: Lexent Bio, Inc.; Shareholder / Stockholder / Stock options: Myriad. R. Srivas: Shareholder / Stockholder / Stock options, Full / Part-time employment: Lexent Bio, Inc. N. Lambert: Shareholder / Stockholder / Stock options, Full / Part-time employment: Lexent Bio, Inc.; Shareholder / Stockholder / Stock options: Sequenom. T. Wilson: Shareholder / Stockholder / Stock options, Full / Part-time employment: Lexent Bio, Inc.; Shareholder / Stockholder / Stock options, Full / Part-time employment, Prior employment: Illumina; Shareholder / Stockholder / Stock options: Counsyl. P. George: Shareholder / Stockholder / Stock options, Full / Part-time employment: Lexent Bio, Inc.; Shareholder / Stockholder / Stock options: Hologic. B. Wong: Shareholder / Stockholder / Stock options, Full / Part-time employment: Lexent Bio, Inc. J. Close: Shareholder / Stockholder / Stock options, Full / Part-time employment: Lexent Bio, Inc. H. Wood: Shareholder / Stockholder / Stock options, Full / Part-time employment: Lexent Bio, Inc. A. Tezcan: Shareholder / Stockholder / Stock options, Full / Part-time employment: Lexent Bio, Inc. J.C. Spinosa: Shareholder / Stockholder / Stock options, Full / Part-time employment: Lexent Bio, Inc.; Full / Part-time employment: San Diego Blood Bank; Advisory / Consultancy: Gestalt Diagnostics; Advisory / Consultancy: SonicHealthUS. H. Tezcan: Leadership role, Shareholder / Stockholder / Stock options, Full / Part-time employment: Lexent Bio, Inc.; Shareholder / Stockholder / Stock options, 2015-2018: Counsyl. Y.K. Chae: Advisory / Consultancy: Foundation Medicine; Advisory / Consultancy: Boehringer Ingelheim; Advisory / Consultancy, Research grant / Funding (institution): Biodesix; Advisory / Consultancy: Counsyl; Advisory / Consultancy, Speaker Bureau / Expert testimony: AstraZeneca; Advisory / Consultancy: Guardant Health; Advisory / Consultancy: Takeda; Advisory / Consultancy, Speaker Bureau / Expert testimony: Genentech; Advisory / Consultancy: ImmuneOncia; Advisory / Consultancy: Hamni; Speaker Bureau / Expert testimony: Merck; Speaker Bureau / Expert testimony: Eli Lilly; Research grant / Funding (institution): Abbvie; Research grant / Funding (institution): Bristol-Myers Squibb; Research grant / Funding (institution): Lexent Bio, Inc.; Research grant / Funding (institution): Freenome. All other authors have declared no conflicts of interest.
Resources from the same session
1117 - Biomarkers predictive of overall survival in advanced cancer patients treated with a peptide-based cancer vaccine.
Presenter: Shigetaka Suekane
Session: Poster Display session 3
Resources:
Abstract
1922 - Expression of PD-L1 in plasma exosomes of NSCLC patients and its associations with PD-L1 expression of corresponding tumor tissues
Presenter: Shaorong Yu
Session: Poster Display session 3
Resources:
Abstract
5495 - Patient’s perspective on digital biomarkers in advanced urologic malignancies
Presenter: Severin Rodler
Session: Poster Display session 3
Resources:
Abstract
3166 - A comprehensive Pan-cancer study of FGFR Aberrations in Chinese cancer patients
Presenter: Yang Gao
Session: Poster Display session 3
Resources:
Abstract
3277 - A Systemic Inflammation Response Index (SIRI) correlates with survival and could be a Predictive Factor for mFOLFIRINOX in Metastatic Pancreatic Cancer (PC)
Presenter: Vilma Pacheco-Barcia
Session: Poster Display session 3
Resources:
Abstract
2680 - Circulating biomarkers and risk of immune-related adverse events (irAEs) in patients (pts) with advanced Non-small cell lung cancer (aNSCLC) and metastatic melanoma (mMel)
Presenter: Alberto Pavan
Session: Poster Display session 3
Resources:
Abstract
4066 - Breast cancer in young women of Kazakh population depending on germline mutations: results of next-generation sequencing
Presenter: Dilyara Kaidarova
Session: Poster Display session 3
Resources:
Abstract
5514 - Discovery of an ImmunoTranscriptomics signature in blood for early colorectal cancer detection
Presenter: Paolo Angelino
Session: Poster Display session 3
Resources:
Abstract
1595 - Serum Netrin-1 as a Biomarker for Colorectal Cancer Detection
Presenter: Jinzhou Zhu
Session: Poster Display session 3
Resources:
Abstract
2036 - Salivary metabolomics for colorectal cancer detection
Presenter: Hiroshi Kuwabara
Session: Poster Display session 3
Resources:
Abstract