# Omitting anthracyclines for the adjuvant treatment of patients with triple-negative breast cancer: A non-inferiority meta-analysis

## TL;DR

This study finds that avoiding anthracyclines in chemotherapy for early-stage triple-negative breast cancer may be as effective as standard treatment, especially for recurrence, but results vary due to patient differences.

## Contribution

The study provides the first meta-analysis evaluating non-inferiority of anthracycline-free regimens in triple-negative breast cancer adjuvant treatment.

## Key findings

- Anthracycline-free chemotherapy showed non-inferiority for recurrence risk compared to standard regimens.
- Taxane-only regimens demonstrated stronger non-inferiority than broader anthracycline-free regimens.
- Non-inferiority was not confirmed for risk of death, with results crossing the non-inferiority margin.

## Abstract

For patients diagnosed with triple-negative breast cancer (TNBC), the sequential use of anthracyclines and taxanes is the standard adjuvant treatment, when this is indicated. However, anthracycline-related toxicities represent a concern. We conducted a meta-analysis to assess whether anthracycline-free regimens are non-inferior to standard, sequential regimens.

We used a complex search strategy to query multiple databases. The population included patients who underwent primary surgery for TNBC, eligible for adjuvant chemotherapy and randomised in a phase 2 or 3 clinical trial. We fitted non-inferiority (NI) margins using published treatment effects. We calculated risk ratios (RR) for recurrence or death.

Eight studies out of 3410 potentially eligible records were included in the meta-analysis, for an overall population of 4292 patients. The RR for recurrence was 1.05 (95 % confidence interval (CI) 0.93–1.19), with an upper bound superimposing on the NI margin of 1.19. In a sensitivity analysis excluding the two studies using CMF, the recurrence RR for the comparison between taxane-only chemotherapy and anthracycline-based sequential chemotherapy was RR 0.97 (95 % CI 0.84–1.11). The RR for death was 1.17 (95 % CI 1.00–1.37), with an upper bound crossing the NI margin of 1.16.

Anthracycline-free adjuvant chemotherapy may represent an option for patients with early TNBC who are not eligible for pre-operative treatment and for whom sparing anthracyclines should be considered (e.g., young patients with small tumours, patients at risk of adverse effects). Non-inferiority was more evident for taxane-only chemotherapy than for anthracycline-free regimens at large. However, our results call for caution considering the remarkable heterogeneity in the study patient populations. This meta-analysis should prompt further research into strategies for patient selection, including the use of prognostic biomarkers for risk stratification.

•The use of adjuvant anthracyclines may be associated with long-term toxicities.•We assessed the impact of omitting adjuvant anthracyclines on outcomes of TNBC patients.•Anthracycline-free chemotherapy proved to be non-inferior to sequential adjuvant chemotherapy, with the strongest, pooled effect being observed for taxane-only regimens.•Non-inferiority was proved for the risk of recurrence, but not for the risk of death.•Our findings may be relevant to a low-risk population undergoing upfront surgery, but caution is warranted given the heterogeneity of the studies.

The use of adjuvant anthracyclines may be associated with long-term toxicities.

We assessed the impact of omitting adjuvant anthracyclines on outcomes of TNBC patients.

Anthracycline-free chemotherapy proved to be non-inferior to sequential adjuvant chemotherapy, with the strongest, pooled effect being observed for taxane-only regimens.

Non-inferiority was proved for the risk of recurrence, but not for the risk of death.

Our findings may be relevant to a low-risk population undergoing upfront surgery, but caution is warranted given the heterogeneity of the studies.