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ePoster Display

152P - Meta-analysis of the prognostic value of circulating tumor DNA (ctDNA) in patients (pts) with early breast cancer (EBC)

Date

16 Sep 2021

Session

ePoster Display

Topics

Tumour Site

Breast Cancer

Presenters

Nadia Saoudi Gonzalez

Citation

Annals of Oncology (2021) 32 (suppl_5): S407-S446. 10.1016/annonc/annonc687

Authors

N. Saoudi Gonzalez1, A. Papakonstantinou2, I. Pimentel2, A. Suñol1, M. Bellet1, E. Zamora1, C. Ortiz1, C. Saura Manich2, G. Villacampa Javierre3, M. Oliveira2

Author affiliations

  • 1 Medical Oncology Dept., Vall d'Hebron University Hospital, 08035 - Barcelona/ES
  • 2 Medical Oncology Dept., Vall d'Hebron University Hospital, 8035 - Barcelona/ES
  • 3 Statistics Department, Vall d'Hebron Institute of Oncology (VHIO)-Cellex Center, 08035 - Barcelona/ES

Resources

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Abstract 152P

Background

Some studies suggest that detection and tracking of ctDNA in early breast cancer (EBC) may predict risk of clinical recurrence, but robust prospective data are missing. We performed a systematic review and meta-analysis (MA) of studies exploring ctDNA as a biomarker for pathologic complete response (pCR) and survival outcomes in pts with EBC receiving neoadjuvant chemotherapy (NACT).

Methods

Following the PRISMA guidelines, we conducted a systematic search in Medline, Web of Science, PubMed, Cochrane and LibraryOpen Grey. Inclusion criteria was: (i) observational studies, prospective or retrospective, and randomized control trials (RCT), ii) human studies, iii) breast cancer patients undergoing neoadjuvant systemic therapy of any type, iv) documented serial serum ctDNA and outcome data such as pCR, DFS or EFS or RFS or DDFS and OS. Study quality was assessed with REMARK score and a funnel plot assessed risk of bias. The endpoints were: i) positive (PPV) and negative predict value (NPV) of ctDNA for pCR; ii) impact of ctDNA at baseline and after NACT on relapse free survival (RFS) and overall survival (OS); iii) odds ratio (OR) for pCR depending on the ctDNA at baseline and iv) subgroup analysis for impact of ctDNA post-surgery on RFS in triple-negative breast cancer (TNBC). ctDNA was treated as a binary variable for all comparisons.

Results

We identified 199 articles, 11 of which met the eligibility criteria and were included in the meta-analysis. Overall, there was no association between baseline ctDNA and pCR (OR 0.93; 95%CI 0.32 – 2.66) and the diagnostic accuracy of cDNA for pCR was low (PPV 0.24 and NPV 0.65). However, presence of ctDNA at baseline was related to worse RFS (HR 4.22, 95%CI 1.29 – 13.8) and worse OS (HR 19.1; 95%CI 6.9 – 53). Moreover, the persistence of ctDNA after NACT was predictive for worse RFS (HR 5.67; 2.73 – 11.75) and OS (HR 4; 1.9 - 8.42). In the subgroup of TNBC, presence of ctDNA after NACT and surgery was also related with worse RFS (HR 3.46; 1.93; 6.18).

Conclusions

Shredding of ctDNA at baseline and especially after NACT identifies a subset of patients with worse prognosis and may be an additional tool to select patients requiring treatment escalation or consider de-escalation.

Clinical trial identification

Editorial acknowledgement

Legal entity responsible for the study

The authors.

Funding

Has not received any funding.

Disclosure

M. Bellet: Financial Interests, Personal, Advisory Board: Lilly; Financial Interests, Personal, Advisory Board: Novartis; Financial Interests, Personal, Advisory Board: PFizer; Financial Interests, Personal, Other, Travel Expenses: Pfizer; Financial Interests, Personal, Speaker’s Bureau: Pfizer; Financial Interests, Personal, Speaker’s Bureau: Novartis; Financial Interests, Personal, Speaker’s Bureau: Lilly. E. Zamora: Financial Interests, Personal, Other, personal fees: Roche; Financial Interests, Personal, Other, personal fees: Novartis; Non-Financial Interests, Personal, Other, non-financial support: Lilly. C. Saura Manich: Financial Interests, Personal, Other, I have served as consultant, participated in advisory boards or received travel grants: AstraZeneca; Financial Interests, Personal, Other, I have served as consultant, participated in advisory boards or received travel grants: Daiichi Sankyo; Financial Interests, Personal, Other, I have served as consultant, participated in advisory boards or received travel grants: Eisai; Financial Interests, Personal, Other, I have served as consultant, participated in advisory boards or received travel grants: Exact Sciences; Financial Interests, Personal, Other, I have served as consultant, participated in advisory boards or received travel grants: Exeter Pharma; Financial Interests, Personal, Other, I have served as consultant, participated in advisory boards or received travel grants: F. Hoffmann-La Roche Ltd.; Financial Interests, Personal, Other, I have served as consultant, participated in advisory boards or received travel grants: Merck Sharp & Dohme; Financial Interests, Personal, Other, I have served as consultant, participated in advisory boards or received travel grants: Novartis; Financial Interests, Personal, Other, I have served as consultant, participated in advisory boards or received travel grants: Pfizer; Financial Interests, Personal, Other, I have served as consultant, participated in advisory boards or received travel grants: Philips; Financial Interests, Personal, Other, I have served as consultant, participated in advisory boards or received travel grants: Pierre Fabre; Financial Interests, Personal, Other, I have served as consultant, participated in advisory boards or received travel grants: Puma; Financial Interests, Personal, Other, I have served as consultant, participated in advisory boards or received travel grants: Roche; Financial Interests, Personal, Other, I have served as consultant, participated in advisory boards or received travel grants: Sanofi-Aventis; Financial Interests, Personal, Other, I have served as consultant, participated in advisory boards or received travel grants: Seagen; Financial Interests, Personal, Other, I have served as consultant, participated in advisory boards or received travel grants: Zymeworks. G. Villacampa Javierre: Financial Interests, Personal, Advisory Role, advisory/consultancy fees: AstraZeneca; Financial Interests, Personal, Expert Testimony: MSD. A.M. Antunes De Melo e Oliveira: Financial Interests, Institutional, Research Grant: AstraZeneca; Financial Interests, Institutional, Research Grant: Philips Healthcare; Financial Interests, Institutional, Research Grant: Genentech; Financial Interests, Institutional, Research Grant: Roche; Financial Interests, Institutional, Research Grant: Genetech; Financial Interests, Institutional, Research Grant: Novartis; Financial Interests, Institutional, Research Grant: Immunomedics; Financial Interests, Institutional, Research Grant: Seattle Genetics; Financial Interests, Institutional, Research Grant: GSK; Financial Interests, Institutional, Research Grant: Boehringer Ingelheim; Financial Interests, Institutional, Research Grant: PUMA Biotechnology; Financial Interests, Personal, Advisory Role: Roche/Genentech; Financial Interests, Personal, Advisory Role: GSK; Financial Interests, Personal, Advisory Role: PUMA; Financial Interests, Personal, Advisory Role: Biotechnology; Financial Interests, Personal, Advisory Board: AstraZeneca; Financial Interests, Personal, Other, Honoraria: Roche; Financial Interests, Personal, Other, Honoraria: Seattle Genetics; Financial Interests, Personal, Other, Honoraria Grants: Novartis; Financial Interests, Personal, Other, Travel Grants: Roche; Financial Interests, Personal, Other, Travel Grants: Pierre-Fabre; Financial Interests, Personal, Other, Travel Grants: Novartis. All other authors have declared no conflicts of interest.

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