Episode 4: Critical Analysis of Oxford’s Controversial Meta-Analysis on Anthracyclines in Breast Cancer

Breast cancer treatment, particularly the use of anthracyclines, has long been a focus of study due to its association with cardiotoxicity. Oxford’s recent meta-analysis, scrutinising the efficacy of anthracyclines versus taxanes in approximately 18,000 patients, has sparked considerable debate within the scientific community.

The meta-analysis suggests that the concurrent administration of anthracycline and taxane yields superior outcomes compared to non-anthracycline regimens. However, a closer examination of the data reveals nuances that prompt a more cautious interpretation.

The TAC regimen, a combination of taxane and anthracycline, demonstrates improved patient outcomes but is hindered by its substantial toxicity, making it less feasible for widespread use. Conversely, the use of a non-anthracycline-taxane combination (TC = docetaxel and cyclophosphamide) shows no significant difference, challenging the notion of anthracycline necessity.

Subgroup analyses expose intriguing patterns. Anthracyclines appear beneficial for hormone receptor-negative, node-negative or node-positive patients, particularly the triple-negative subtype. In contrast, HR-positive patients, irrespective of nodal status, do not exhibit a clear advantage, raising questions about the universality of anthracycline use.

Modern tools, including genomic testing, provide alternative means to determine the necessity of chemotherapy. For high-risk cases, particularly triple-negative and HER2-positive tumours with significant burdens, anthracyclines may still hold relevance. However, judicious patient selection is paramount, considering the potential short and long-term toxicities associated with anthracycline use.

The meta-analysis is critiqued for amalgamating diverse datasets, resulting in conclusions driven by a combination of anthracycline-taxane regimens rarely employed in practice and the influence of hormone receptor status, specifically ER-negative disease.

In conclusion, the meta-analysis’s impact on clinical practice is deemed limited, emphasising the importance of discerning relevant questions in breast cancer research. The nuanced use of anthracyclines, particularly in light of evolving diagnostic tools and patient-specific considerations, remains a subject of ongoing discussion within the scientific and medical communities.

Ref : Gabe S. Sonke et al., Primary outcome analysis of the phase 3 SONIA trial (BOOG 2017-03) on selecting the optimal position of CDK4/6 inhibitors for patients with HR+, HER2 advanced breast cancer (ABC); Meeting Abstract LBA1000, 2023 ASCO Annual Meeting.