Abstract 186P
Background
Event-free survival (EFS) is a commonly used primary endpoint in neoadjuvant studies for triple-negative breast cancer (TNBC) as overall survival (OS) requires extended follow-up and significant patient resources. However, the surrogacy of EFS for OS has yet to be established. This study evaluated the association between EFS and OS among early-stage TNBC patients who received neoadjuvant therapy.
Methods
A literature search of neoadjuvant studies in early-stage TNBC was conducted up to March 2022. Clinical trials (CTs), real-world evidence (RWE) studies and meta-analyses that reported both EFS and OS outcomes were included. Weighted linear regression analyses were conducted based on landmark EFS and OS rates to assess the individual-level association between EFS and OS. The trial-level association between the treatment effects on EFS and on OS was assessed based on the logarithmic scale of hazard ratios (HRs) of EFS and OS in randomized controlled trials (RCTs). The coefficient of determinations (R2) was used to measure the strength of the associations. Sensitivity analyses were conducted to assess the impact of divergent study characteristics.
Results
Forty-five studies (12 RCTs, 2 single-arm CTs and 31 RWE studies) for a total 7533 patients with TNBC were eligible for the patient-level analysis. The results showed that 3-year EFS was a significant predictor of 5-year OS rate [P<0.01; R2: 0.82 (95% CI: 0.68-0.91)]. A strong correlation was also found between 3-year EFS and 3-year OS rate and between 5-year EFS and 5-year OS rate. The trial-level analyses included 19 between-treatment comparisons from 15 RCTs. There was a statistically significant relationship between the treatment effect on EFS and OS (P<0.001), with an R2 of 0.64 (95% CI: 0.45-0.82). Consistent results were found in the sensitivity analyses.
Conclusions
This study demonstrates a significant association between EFS and OS and suggests EFS as a valid surrogate for OS in early-stage TNBC following neoadjuvant therapy. The findings support the use of EFS in the regulatory and reimbursement approvals of new anti-cancer treatments in this setting.
Clinical trial identification
Editorial acknowledgement
Legal entity responsible for the study
Merck & Co., Inc.
Funding
Merck & Co., Inc.
Disclosure
P.A. Fasching: Financial Interests, Personal, Advisory Board: Roche, Novartis, Pfizer, Daiichi Sankyo, Eisai, Merck, Sharp & Dohme, Astrazeneca, Hecal, Lilly, Pierre Fabre, Seagen, Agendia; Financial Interests, Personal, Invited Speaker: Novartis, Daiichi Sankyo, Eisai, Merck, Sharp & Dohme, AstraZeneca, Lilly, Seagen; Financial Interests, Personal, Other, Medical Writing Support: Roche; Financial Interests, Institutional, Invited Speaker: BionTech, Cepheid; Non-Financial Interests, Member: ASCO, Arbeitsgemeinschaft für Gynäkologische Onkologie e.V., Translational Research in Oncology, Deutsche Gesellschaft für Senologie e.v. M. Huang, A. Haiderali, W. Pan, V. Karantza: Financial Interests, Personal, Full or part-time Employment: Merck & Co., Inc. W. Xue, F. Yang, J. Truscott, Y. Xin: Financial Interests, Personal, Full or part-time Employment, Analysis Group recevies funding from Merck & Co. to conduct this research.: Analysis Group. J. O'Shaughnessy: Financial Interests, Personal, Advisory Board: AbbVie, Agendia, Amgen, Aptitude Health, AstraZeneca, Bristol-Myers Squibb, Celgene, Eisai, G1 Therapeutics, Genentech, Immunomedics, Ipsen Biopharmaceuticals, Lilly, Merck, Myriad, Novartis, Ondonate, Pfizer, Puma, Prime Oncology, Roche, Seattle Genetics, Syndax, Carrick Therapeutics, Daiichi Sankyo, Gilead Sciences, Ontada, Pierre Fabre Pharmaceuticals, Samsung Bioepis, Sanofi.