Abstract 1415P
Background
Most gastroesophageal cancers (GEC) recur after curative intent therapy, and the prognosis for advanced disease remains poor. Specific and sensitive tools to identify patients at risk for recurrence and/or progression are needed. Previous studies have shown detection of molecular/minimal residual disease (MRD) using tumor-informed circulating tumor DNA (ctDNA) assays is associated with risk of recurrence in colorectal cancer. There is limited data and an unmet need to describe clinical performance of MRD assays in GEC.
Methods
A personalized and tumor-informed multiplex PCR assay (Signatera™ bespoke mPCR NGS assay) was used for the detection and quantification of ctDNA in a prospective clinical cohort of patients. Serial time points were collected for a subset of patients to monitor their ctDNA levels in response to treatment.
Results
Here we analyzed 691 plasma samples from a total of 254 patients with esophageal (n=76), esophagogastric junction (GEJ, n=68), and gastric (n=110) carcinoma. ctDNA-positivity rates and quantification (mean tumor molecules/mL) are presented in the Table. Median follow up from time of surgery was 254 days (range 7-1,981). In the postoperative setting, within the first 16 weeks, 29.7% (27/92) of the patients were MRD-positive. Among stage IV patients, 64% (44/69) were observed to be MRD-positive, irrespective of the treatment. MRD detection was associated with shorter relapse free and progression free survival rates.
Conclusions
Here we describe a large, real-world study reporting results from a clinically validated tumor-informed, ctDNA-based MRD assay in a GEC cohort. Our data informs design of future prospective validation studies to establish the utility of a tumor-informed assay for MRD detection and surveillance monitoring in GEC. Table: 1415P
ctDNA-positivity rates in patients with esophageal and gastric cancer
| Stages | Patients, N (%) | Anytime ctDNA-positivity, N (%) | ctDNA (MTM/mL), Mean (Range) |
| Esophageal Adenocarcinoma | |||
| Stage I-III | 49 (86) | 23 (46.9) | 50.6 (0.01-3061.7) |
| Stage IV | 8 (14) | 5 (62.5) | 37.3 (0.06-248.5) |
| Esophageal Squamous | |||
| Stage II/III | 11 (68.8) | 4 (36.4) | 1.8 (0.02-15.7) |
| Stage IV | 5 (31.2) | 4 (80) | 814.2 (0.05-6244.5) |
| Gastroesophageal Junction (GEJ) Adenocarcinoma | |||
| Stage I-III | 47 (70.1) | 17 (36.2) | 51.1 (0.01-1829.2) |
| Stage IV | 20 (29.9) | 13 (65) | 196.9 (0.01-5113.7) |
| Gastric Adenocarcinoma | |||
| Stage I-III | 75 (68.2) | 17 (22.6) | 17.8 (0.01-1155.4) |
| Stage IV | 35 (31.8) | 23 (65.7) | 44.9 (0.03-1120.9) |
| Esophageal/Gastric and Other Histologies | |||
| Stage III | 3 (75) | 1 (33.3) | 0.3 (0.01-0.9) |
| Stage IV | 1 (25) | 1 (100) | 0.2 (0.23-0.2) |
Clinical trial identification
Editorial acknowledgement
Legal entity responsible for the study
The authors.
Funding
Natera, Inc.
Disclosure
G. Budde: Financial Interests, Personal, Full or part-time Employment: Natera, Inc.; Financial Interests, Personal, Stocks/Shares: Natera, Inc. F. Dayyani: Financial Interests, Personal, Speaker’s Bureau: Amgen, Deciphera, Eisai, Exelixis, Ipsen, Natera, Sirtex; Financial Interests, Personal, Advisory Board: AZD, Eisai, Exelixis, FMI, Genentech/Roche, QED, Natera; Financial Interests, Personal, Full or part-time Employment, Spouse: Roche Diagnostics; Financial Interests, Institutional, Research Grant: Amgen, AZD, BMS, Bayer, Exelixis, Genentech/Roche, Ipsen, Natera, Merck, Taiho, Trishula. G. Botta: Financial Interests, Personal, Advisory Board: Natera, Inc.; Financial Interests, Personal, Speaker’s Bureau: Natera, Inc.; Financial Interests, Personal, Other, Consultant: CEND Therapeutics. S. Krinshpun: Financial Interests, Personal, Full or part-time Employment: Natera, Inc.; Financial Interests, Personal, Stocks/Shares: Natera, Inc. S. Sharma: Financial Interests, Personal, Full or part-time Employment: Natera, Inc.; Financial Interests, Personal, Stocks/Shares: Natera, Inc. V. Aushev: Financial Interests, Personal, Full or part-time Employment: Natera, Inc.; Financial Interests, Personal, Stocks/Shares: Natera, Inc. T. Farmer: Financial Interests, Personal, Full or part-time Employment: Natera, Inc.; Financial Interests, Personal, Stocks/Shares: Natera, Inc. H. Pela: Financial Interests, Personal, Full or part-time Employment: Natera, Inc.; Financial Interests, Personal, Stocks/Shares: Natera, Inc. M. Tavallai: Financial Interests, Personal, Full or part-time Employment: Natera, Inc.; Financial Interests, Personal, Stocks/Shares: Natera, Inc. M. Goodman: Financial Interests, Personal, Full or part-time Employment: Natera, Inc.; Financial Interests, Personal, Stocks/Shares: Natera, Inc. K. Baker: Financial Interests, Personal, Full or part-time Employment: Natera, Inc.; Financial Interests, Personal, Stocks/Shares: Natera, Inc. B. Drummond: Financial Interests, Personal, Full or part-time Employment: Natera, Inc.; Financial Interests, Personal, Stocks/Shares: Natera, Inc. A. Aleshin: Financial Interests, Personal, Full or part-time Employment: Natera, Inc.; Financial Interests, Personal, Stocks/Shares: Natera, Inc.; Financial Interests, Personal, Leadership Role: Natera, Inc.; Non-Financial Interests, Personal, Ownership Interest, Advisory: Mission Bio; Non-Financial Interests, Personal, Ownership Interest, Advisory: Notable Labs. S.J. Klempner: Financial Interests, Personal, Advisory Board: Eli Lilly; Financial Interests, Personal, Advisory Board: Merck; Financial Interests, Personal, Advisory Board: BMS; Financial Interests, Personal, Advisory Board: Daiichi Sankyo; Financial Interests, Personal, Advisory Board: Astellas; Financial Interests, Personal, Advisory Board: Natera; Financial Interests, Personal, Advisory Board: Pieris; Financial Interests, Personal, Stocks/Shares: Turning Point Therapeutics. All other authors have declared no conflicts of interest.