95MO - Circulating tumor DNA (ctDNA) dynamics in patients (pts) receiving capecitabine (CAPE) for early-stage triple-negative breast cancer (eTNBC) with an incomplete response to neoadjuvant therapy (NAT)

Background

Adjuvant CAPE is the standard-of-care (SoC) in eTNBC pts with incomplete response to anthracycline-based NAT. Presence of ctDNA following standard therapy in early breast cancer is associated with poor relapse-free survival (RFS). Here, we evaluated the rates of ctDNA detection before, during and after adjuvant CAPE.

Methods

Pts with residual disease after NAT receiving adjuvant CAPE for 6 months (+/- pembrolizumab) were enrolled in 2 separate, prospective ctDNA monitoring studies. Plasma samples for ctDNA detection (SignateraTM, bespoke mPCR-NGS assay) were collected before, during and after CAPE. Association between ctDNA detection and residual cancer burden (RCB) scores and pathologic stage were evaluated using chi square test. Correlation of ctDNA status with outcomes was evaluated using log-rank test.

Results

Median follow up was 19.3 months (range: 10.7-43.7). A total of 29 pts with a median age of 43 years (range: 33-78) were included. RCB scores after NAT were available for 26 pts (I:10, II:12, III:4). ctDNA positivity during CAPE was significantly higher in pts with RCB III (p=0.0082) and pN3 (p=0.0072). Detection of ctDNA was 15% (3/20) prior to and 25% (7/28) after completion of CAPE. Treatment with CAPE did not result in ctDNA clearance for any pts. Among the 7 pts who were ctDNA-positive, after CAPE, 6 (86%) subsequently experienced clinical relapse with a median of 3.85 months (range: 0.6-11). ctDNA-positivity was strongly associated with inferior RFS (ctDNA-positive: 14% vs ctDNA-negative: 100%; p=0.0001). Only one pt died, 13 months after testing ctDNA-positive prior to CAPE, resulting in an overall survival of 97%.

Conclusions

Treatment with CAPE failed to achieve ctDNA clearance in eTNBC pts who were ctDNA-positive prior to CAPE. ctDNA-positive status was associated with poor RFS in this high-risk population. ctDNA persistence on CAPE may prove useful as a biomarker to select patients for novel agents in adjuvant trials.

Clinical trial identification

NCT04768426.

Legal entity responsible for the study

The authors.

Funding

Only the ctDNA testing in our study is being covered by the company Natera (through their early adopter program). The rest of the study is not funded by the company.

Disclosure

T. Gupta: Financial Interests, Personal, Other, Support: ASCO Gianni Bonadonna Breast Cancer Research Fellowship; Financial Interests, Personal, Advisory Board: Gilead, Biotheranostics. E. Kalashnikova, A.A. Rodriguez: Financial Interests, Personal, Full or part-time Employment: Natera; Financial Interests, Personal, Stocks/Shares: Natera. M.C. Liu: Financial Interests, Personal, Full or part-time Employment: Natera; Financial Interests, Personal, Stocks/Shares: Natera; Financial Interests, Institutional, Research Grant: Eisai, Exact Sciences, Genentech, Genomic Health, GRAIL, Menarini Silicon Biosystems, Merck, Novartis, Seattle Genetics, Tesaro; Financial Interests, Institutional, Advisory Board: AstraZeneca, Celgene, Roche/Genentech, Genomic Health, GRAIL, Ionis, Merck, Pfizer, Seattle Genetics, Syndax; Financial Interests, Personal, Other, Travel reimbursement: AstraZeneca, Genomic Health, Ionis. A.J. Medford: Financial Interests, Personal, Advisory Role: Natera, Illumina. S. Isakoff: Financial Interests, Personal, Funding: AstraZeneca, Genentech, Merck, Oncopep. A. Bardia: Financial Interests, Personal, Advisory Board: Pfizer, Novartis, Genentech, Merck, Radius Health, Immunomedics/Gilead, Sanofi, Daiichi Pharma/AstraZeneca, Phillips, Eli Lily, Foundation Medicine; Financial Interests, Institutional, Research Grant: Genentech, Novartis, Pfizer, Merck, Sanofi, Radius Health, Immunomedics/Gilead, Daiichi Pharma/AstraZeneca, Eli Lily. M.L. Telli: Financial Interests, Institutional, Research Grant: AbbVie, Arvinas, Bayer, Biothera, Calithera Biosciences, EMD Serono, Genentech, GlaxoSmithKline, Hummingbird Biosciences, Medivation, Merck, Novartis, OncoSec, Pfizer, PharmaMar, Tesaro, Vertex; Financial Interests, Personal, Advisory Role: AbbVie, Aduro Biotech, AstraZeneca, Blueprint Medicines, Daiichi Sankyo, Genentech/Roche, Gilead, GlaxoSmithKline, G1 Therapeutics, Guardant, Immunomedics, Merck, Natera, Novartis, OncoSec, Pfizer, RefleXion, Replicate, Sanofi. A.Y. Ho: Financial Interests, Personal, Funding: Merck, GSK, Natera, Breast Cancer Research Foundation; Financial Interests, Personal, Research Grant, R01 CA274254: National Institutes of Health. All other authors have declared no conflicts of interest.