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
5105 - Fresh blood Immune cell monitoring in patients treated with nivolumab in the GETUG-AFU26 NIVOREN study: association with toxicity and treatment outcome
Presenter: Aude DESNOYER
Session: Poster Display session 3
Resources:
Abstract
1877 - Advanced clear-cell renal cell carcinoma (accRCC): association of microRNAs (miRNAs) with molecular subtypes, mRNA targets and outcome.
Presenter: Annelies Verbiest
Session: Poster Display session 3
Resources:
Abstract
5543 - Prior tyrosine kinase inhibitors (TKI) and antibiotics (ATB) use are associated with distinct gut microbiota ‘guilds’ in renal cell carcinoma (RCC) patients
Presenter: Valerio Iebba
Session: Poster Display session 3
Resources:
Abstract
2689 - mTOR mutations are not associated with shorter PFS and OS in patients treated with mTOR inhibitors
Presenter: Cristina Suarez Rodriguez
Session: Poster Display session 3
Resources:
Abstract
3069 - Efficacy of immune checkpoint inhibitors (ICI) and genomic alterations by body mass index (BMI) in Advanced Renal Cell Carcinoma (RCC)
Presenter: Aly-Khan Lalani
Session: Poster Display session 3
Resources:
Abstract
5089 - Finding the Right Biomarker for Renal Cell Carcinoma (RCC): Nivolumab treatment induces the expression of specific peripheral lymphocyte microRNAs in patients with durable and complete response.
Presenter: Lorena Incorvaia
Session: Poster Display session 3
Resources:
Abstract
2594 - Algorithms derived from quantitative pathology can be a gatekeeper in patient selection for clinical trials in localised clear cell renal cell carcinoma (ccRCC)
Presenter: In Hwa Um
Session: Poster Display session 3
Resources:
Abstract
2566 - High baseline blood volume is an independent favorable prognostic factor for overall and progression-free survival in patients with metastatic renal cell carcinoma
Presenter: Aska Drljevic-nielsen
Session: Poster Display session 3
Resources:
Abstract
2675 - Impact of estimand selection on adjuvant treatment outcomes in renal cell carcinoma (RCC)
Presenter: Daniel George
Session: Poster Display session 3
Resources:
Abstract
1541 - TERT gene fusions characterize a subset of metastatic Leydig cell tumors
Presenter: Bozo Kruslin
Session: Poster Display session 3
Resources:
Abstract