96MO - Omitting anthracyclines for the adjuvant treatment of patients with triple-negative breast cancer (TNBC): a non-inferiority meta-analysis

Background

Sequential anthracyclines (A) plus taxanes represent a standard adjuvant regimen for early TNBC patients. The potential risk for long-term toxicities led to studies exploring the use of A-free options with partly inconsistent results. We here addressed this question by conducting a non-inferiority meta-analysis.

Methods

We queried Embase, MEDLINE, PubMed, ASCO, and ESMO proceedings to identify randomised clinical trials comparing A-free and A-based regimens. Given the differences in study design, we applied the raw number of events to calculate the risk ratios (RR) for recurrence or death. The non-inferiority (NI) margin was defined as the inverse of the product of the unconfounded treatment effects of A plus taxanes versus A, and A versus no chemotherapy, based on estimates from the EBCTCG 2012 meta-analysis on adjuvant chemotherapy. To improve the specificity, a conservative NI margin was defined using the upper bounds (UB) of the EBCTCG confidence intervals (CI).

Results

We retrieved 3,317 potentially eligible records and 8 studies were included in the meta-analysis (4,328 patients in total). The median follow-up time was in the range of 40-97 months. The RR for recurrence with A-free compared to A-based therapy was 1.06, with the UB of the 95% CI (0.93-1.21) falling within the NI margin (1.75). Using the conservative NI margin for recurrence (1.43), A-free regimens still proved non-inferior. A sensitivity analysis excluding trials using CMF as an A-free regimen showed similar results (RR 0.97, 95% CI 0.83-1.12). The RR for death from any cause with A-free compared to A-based therapy was 1.12, with the UB of the 95% CI (0.92-1.36) falling within the NI margin (1.4). A-free regimens did not prove non-inferior to A-based chemotherapy when using the 1.15 conservative NI margin.

Conclusions

In the largest meta-analysis to date, A-free regimens proved non-inferior to A-based adjuvant therapy for risk of recurrence. However, non-inferiority could not be shown for risk of death when applying a conservative NI margin. These results may support the adoption of A-free regimens. The observed, substantial study heterogeneity calls for caution when interpreting these findings.

Legal entity responsible for the study

The authors.

Funding

Has not received any funding.

Disclosure

F. Girardi: Financial Interests, Personal, Invited Speaker: AstraZeneca; Financial Interests, Personal, Other, Travel Support: Gilead Sciences, Eli Lilly. G. Griguolo: Financial Interests, Personal, Advisory Board: Gilead Sciences; Financial Interests, Personal, Invited Speaker: Eli Lilly, Novartis; Financial Interests, Personal, Other, Travel Support: Gilead Sciences, Eli Lilly, Pfizer, Novartis, Amgen, Daiichi Sankyo. T. Giarratano: Financial Interests, Personal, Other: Eli Lilly, Roche, Novartis. F. Miglietta: Financial Interests, Personal, Other: Novartis, Roche, Gilead Sciences. M.V. Dieci: Financial Interests, Personal, Advisory Role: Eli Lilly, Novartis, Exact Sciences , Pfizer, Seattle Genetics, MSD, Gilead Sciences. V. Guarneri: Financial Interests, Personal, Invited Speaker: Eli Lilly, Novartis, Amgen, GSK; Financial Interests, Personal, Advisory Board: Eli Lilly, Novartis, MSD, Gilead, Sanofi, Merck Serono, Exact Sciences, Eisai, Olema Oncology; Financial Interests, Personal, Expert Testimony: Eli Lilly; Financial Interests, Institutional, Invited Speaker: Eli Lilly, Roche, BMS, Novartis, AstraZeneca, MSD, Synton Biopharmaceuticals, Merck, GlaxoSmithKline, Daiichi Sankyo, Nerviano; Non-Financial Interests, Member: ASCO. All other authors have declared no conflicts of interest.