Abstract 1224P
Background
Blood-based ECD is an emerging tool to identify cancer signals in asymptomatic individuals. ctDNA detection is impacted by several clinicopathologic factors. We report on ctDNA detection rates in pts with cancer prior to receiving treatment and in correlation with median tumor mutational burden (mTMB) rates.
Methods
Pretreatment plasma samples were analyzed using a tumor-informed ctDNA assay (SignateraTM) in 1657 pts, including breast cancer (BC, N=131), lung cancer (LC, N=57), colorectal cancer (CRC, N=1382), epithelial ovarian cancer (OV, N=36), pancreatic cancer (PC, N=17), and diffuse large B cell lymphoma (DLBCL, N=37). Stage-agnostic, exome-based mTMB was reported for BC, CRC, PC, DLBCL (internal data), LC (pmid28420421), and OV (pmid35087563).
Results
Baseline ctDNA was detected in 1621 (87%) pts; rates were lower in stage I/II (707/858, 82.4%) vs III/IV (914/998, 91.6%). In BC (mTMB 4.4 mut/MB), ctDNA detection rates were lower in hormone receptor-positive tumors (stage I/II 61.2%[74/121], III 81% [17/21]) vs triple-negative breast cancer (I/II 81.5% [75/92], III 97% [58/60]) and HER2+ tumors (I/II 73.9% [17/23], III 87.5% [7/8]); rates increased by stage in all subtypes. In LC, detection rates were lower for adenocarcinoma (mTMB 6.3 mut/MB; I/II 25% [5/20], III 73% [11/15]) vs squamous cell carcinoma (mTMB 9.0 mut/MB; I/II 85% [11/13], III 100% [9/9]). In CRC (mTMB 4.31 mut/MB with a bi-modal distribution), detection rates for stage I/II/III-IV were [(74% (71/96), 94% (421/448) and 92% (773/838)]. In OV (mTMB 1.9 mut/MB), detection rates were 60% (9/15) in stage I/II and 72% (15/21) in stage III/IV. In PC (mTMB 1.47 mut/MB), detection rates were 65% (11/17) in stage I/II and 100% (2/2) in stage III/IV. In DLBCL (mTMB 4.58 mut/MB), detection rates were 100% (13/13) in stage I/II and 92% (22/24) in III/IV.
Conclusions
Our study supports past findings that ctDNA positivity varies across cancers and histology and is higher in some later stage cancers and suggests that ctDNA detection in the presurgical setting can be detected in a majority of patients with a tumor-informed approach. Further studies are needed to understand the biological and technical factors that may impact assay’s performance.
Clinical trial identification
Editorial acknowledgement
Legal entity responsible for the study
The authors.
Funding
Has not received any funding.
Disclosure
Y. Nakamura: Financial Interests, Personal, Invited Speaker: Chugai, Merck Biopharma, Guardant Health AMEA; Financial Interests, Institutional, Funding: Taiho, Chugai, Guardant Health, Genomedia, Daiichi Sankyo, Roche Diagnostics; Financial Interests, Institutional, Coordinating PI: Seagen. T. Tin, S. Krinshpun, B. Mitchell, S.L. Bristow: Financial Interests, Personal, Full or part-time Employment: Natera; Financial Interests, Personal, Stocks/Shares: Natera. A. Aleshin: Financial Interests, Personal, Full or part-time Employment: Natera; Financial Interests, Personal, Leadership Role: Natera; Financial Interests, Personal, Stocks/Shares: Natera. L.J. Van't Veer: Financial Interests, Personal, Full or part-time Employment: Agendia; Financial Interests, Personal, Stocks/Shares: Agendia; Non-Financial Interests, Personal, Advisory Role: ExaiBio Inc. C. Lindbjerg Andersen: Non-Financial Interests, Personal, Other, Research collaboration: Natera, C2i Genomics. D.S.W. Tan: Financial Interests, Personal, Advisory Board: Amgen, Novartis, Boehringer Ingelheim, C4 Therapeutics, AstraZeneca, GSK, Takeda, Eisai, Guardant, Merck, Pfizer, Roche; Financial Interests, Institutional, Research Grant: AstraZeneca, Amgen, Pfizer, ACM Biolabs; Financial Interests, Personal, Steering Committee Member: Novartis. T. Yoshino: Financial Interests, Personal, Invited Speaker: Chugai Pharmaceutical Co., Ltd., Merck Biopharma Co., Ltd., Bayer Yakuhin, Ltd., Ono Pharmaceutical Co., Ltd., MSD K.K., Takeda Pharmaceutical Co., Ltd.; Financial Interests, Personal, Other, Consultancy: Sumitomo Corp.; Financial Interests, Institutional, Local PI: Ono Pharmaceutical Co., Ltd., Sanofi K.K., Daiichi Sankyo Co., Ltd., MSD K.K., Pfizer Japan Inc., Eisai Co., Ltd.; Financial Interests, Institutional, Research Grant: Taiho Pharmaceutical Co., Ltd., Molecular Health GmbH, Ono Pharmaceutical Co., Ltd., Amgen K.K., Genomedia Inc., Sysmex Corp., Daiichi Sankyo Co., Ltd., Chugai Pharmaceutical Co., Ltd., Nippon Boehringer Ingelheim Co., Ltd., Roche Diagnostics K.K.; Financial Interests, Personal, Research Grant: FALCO Biosystems Ltd. All other authors have declared no conflicts of interest.
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