Abstract 4689
Background
Circulating tumor DNA (ctDNA) has emerged as a promising biomarker for early prediction of relapse across different tumor types. In patients with colorectal cancer (CRC), multiple studies have analyzed ctDNA to monitor tumor burden using fixed gene panels and droplet digital PCR. Here, we use a highly sensitive and specific, bespoke, whole exome-based NGS approach (Signatera™) for ctDNA monitoring.
Methods
A cohort of 33 patients with stage III CRC who underwent surgery and were treated with at least 4 months of adjuvant chemotherapy was analyzed. Mutational profiles derived from primary tumor tissue and germline DNA whole exome were used to design assays targeting tumor-specific somatic variants. The bespoke assays were used for ctDNA detection in plasma samples. Relapse-free survival (RFS) was calculated for patients stratified by ctDNA status.
Results
Plasma samples (n = 44; average volume=1.8mL) from patients (N = 33) were analysed for the presence of ctDNA. Of the five ctDNA-positive patients, clinical follow-up was available for three patients, all of whom relapsed (100%; 3/3); three of 27 ctDNA-negative patients (11%) also clinically relapsed. Molecular relapse through ctDNA analysis was detected up to 668 days ahead of radiological imaging with an average lead time of 305 days. The majority of relapses in ctDNA-positive patients (67%; 2/3) occurred within a year of follow-up, while no relapses were observed in ctDNA-negative patients during the one-year time frame. All plasma samples (n = 34) from 24 non-relapsing patients were ctDNA negative, corresponding to a specificity of 100%. The presence of ctDNA was associated with a markedly reduced RFS compared to ctDNA-negative patients (HR: 5.6; 95% CI: 0.6-52.1; p < 0.01).
Conclusions
The study results indicate that ctDNA status is associated with high relapse risk in patients with CRC and can serve as a predictor of patient outcome. Despite low plasma volumes (<5mL) and lack of longitudinal samples for analysis, ctDNA was detected in 50% of relapse cases.
Clinical trial identification
Editorial acknowledgement
Legal entity responsible for the study
Natera, Inc. and NSABP Foundation.
Funding
Natera, Inc., Bayer, NSABP Foundation.
Disclosure
H. Sethi: Shareholder / Stockholder / Stock options, Full / Part-time employment, I am an employee of Natera and own stock/options to stock.: Natera, Inc. T.J. George: Research grant / Funding (institution): Merck; Research grant / Funding (institution): AstraZeneca; Research grant / Funding (institution): BMS; Research grant / Funding (institution): Bayer; Research grant / Funding (institution): Lilly; Research grant / Funding (institution): Incyte; Research grant / Funding (institution): Seattle Genetics; Research grant / Funding (institution): Pharmacyclics. S. Shchegrova: Shareholder / Stockholder / Stock options, Full / Part-time employment, I am an employee of Natera and own stock/options to stock.: Natera, Inc. A.S. Tin: Shareholder / Stockholder / Stock options, Full / Part-time employment, I am an employee of Natera and own stock/options to stock.: Natera, Inc. A. Olson: Shareholder / Stockholder / Stock options, Full / Part-time employment, I am an employee of Natera and own stock/options to stock.: Natera, Inc. D. Renner: Full / Part-time employment: Natera, Inc. E. Kalashnikova: Full / Part-time employment: Natera, Inc. M. Louie: Shareholder / Stockholder / Stock options, Full / Part-time employment, I am an employee of Natera and own stock/options to stock.: Natera, Inc. R. Salari: Shareholder / Stockholder / Stock options, Full / Part-time employment, I am an employee of Natera and own stock/options to stock.: Natera, Inc. B. Zimmermann: Shareholder / Stockholder / Stock options, Full / Part-time employment, I am an employee of Natera and own stock/options to stock.: Natera, Inc. A. Aleshin: Shareholder / Stockholder / Stock options, Full / Part-time employment, I am an employee of Natera and own stock/options to stock.: Natera, Inc. All other authors have declared no conflicts of interest.
Resources from the same session
1285 - Preliminary results of STELLAR-001, a dose escalation phase I study of the anti-C5aR, IPH5401, in combination with durvalumab in advanced solid tumors.
Presenter: Christophe Massard
Session: Poster Display session 3
Resources:
Abstract
3808 - GOLFIG chemo-immunotherapy in metastatic colorectal cancer (mCRC) patients: A fifteen year retrospective analysis
Presenter: Pierpaolo Correale
Session: Poster Display session 3
Resources:
Abstract
5677 - Immune correlates in peripheral blood samples in a preoperative window of opportunity randomized trial of nivolumab with or without tadalafil in resectable squamous cell carcinoma of the head and neck (SCCHN)
Presenter: Larry Harshyne
Session: Poster Display session 3
Resources:
Abstract
4854 - Phase 1 evaluation of AB928, a novel dual adenosine receptor antagonist, combined with chemotherapy or AB122 (anti-PD-1) in patients (pts) with advanced malignancies
Presenter: John Powderly
Session: Poster Display session 3
Resources:
Abstract
4344 - Phase 1 Trial of CV301 in Combination with Anti-PD-1 Therapy in Non-squamous NSCLC
Presenter: Arun Rajan
Session: Poster Display session 3
Resources:
Abstract
4555 - Safety and efficacy results of the combination of DPX-Survivac, pembrolizumab and intermittent low dose cyclophosphamide (CPA) in subjects with advanced and metastatic solid tumors: preliminary results from the hepatocellular carcinoma (HCC), NSCLC, bladder cancer, & MSI-H cohorts
Presenter: Henry Conter
Session: Poster Display session 3
Resources:
Abstract
3012 - Excellent CBR and Prolonged PFS in Non-Squamous NSCLC with Oral CA-170, an Inhibitor of VISTA and PD-L1
Presenter: Vivek Radhakrishnan
Session: Poster Display session 3
Resources:
Abstract
2536 - Phase Ib/II trial of TG4001 (Tipapkinogene sovacivec), a therapeutic HPV-vaccine, and Avelumab in patients with recurrent/metastatic (R/M) HPV-16+ cancers
Presenter: Christophe Le Tourneau
Session: Poster Display session 3
Resources:
Abstract
1845 - Induction of tumor-infiltrating functional CD8 positive cells and PD-L1 expression in esophageal cancer by S-588410
Presenter: Takashi Kojima
Session: Poster Display session 3
Resources:
Abstract
5043 - Comprehensive results of a Phase Ib study with a HER2/neu B-cell peptide vaccine administered with cisplatin and 5-fluorouracil or capecitabine chemotherapy show safety, immunogenicity and clinical response in patients with HER2/Neu overexpressing advanced gastric cancer
Presenter: Ursula Wiedermann
Session: Poster Display session 3
Resources:
Abstract