Should toxicity be taken into account in determining chemotherapy backbone in HER2-positive (HER2+) early breast cancer (eBC)?

Abstract

e12628 Background: Trastuzumab-Pertuzumab (TP) plus chemotherapy is the standard of care in stage II-III HER2+ eBC, but guidelines give general recommendations, and the optimal chemotherapy backbone is a matter of debate. For more than 50 years, regimens incorporating anthracyclines improved prognosis of patients (pts) with eBC, but now the question is which cancers still need this chemotherapy. Because of the overlap in cardiotoxicity of anthracyclines and antiHER2 drugs, anthracycline-free regimens have been assessed in TRYPHAENA and TRAIN-2. In these two studies, no difference in efficacy was seen between TP regimens with or without anthracyclines. However, in TRAIN-2 anthracyclines use was associated with an increased risk of febrile neutropenia, cardiotoxicity and secondary neoplasms. Methods: Retrospective observational study of HER2+ eBC pts treated with neoadjuvant TP chemotherapy, between February 2015 and May 2022, at University Hospital A Coruña (Spain). Primary endpoint: total pathologic complete response (tpCR) (ypT0/is ypN0). Secondary endpoint: association between toxicity and type of chemotherapy. Statistical analysis was carried out using R system. Results: This study included 156 women diagnosed with stage I-III eBC at University Hospital A Coruña. Median age was 49 years (26-79) and the majority of pts (62.2%) were stage II disease. Neoadjuvant treatment was based on TP plus taxane and platinum or anthracyclines (36.6% vs 62.3 %, respectively). 51.3% of pts achieved tpCR, that was not significantly related to chemotherapy type (platinum vs anthracyclines: 55.6% vs 55.1%; p = 0.734). Diarrhoea occurred in 58.3% cases, mainly CTCAE grade 1-2 (55.1%), and was more common in the platinum group than in those receiving anthracyclines (72.3% vs 53.5%, p = 0.026). 56.41% of pts presented asthenia, mostly CTCAE grade 1-2, with no significant differences between treatment type (p = 0.936). Platinum chemotherapy led to higher and severe haematological toxicity at the end of neoadjuvant therapy: anaemia (90.6% vs 53.6%; CTACE grade 3-4 3.8% vs 0%; p = 0.000), neutropenia (59.3% vs 28.9%; CTACE grade 3-4 5.6% vs 4%; p = 0.003) and thrombopenia (44.4% vs 3.1%; CTACE grade 3-4 3.7% vs 0%; p = 0.000). Febrile neutropenia was more frequent with anthracyclines (83.3%) than platinum (16.7%), not statistically significantly (p = 0.114). Cardiotoxicity occurred in 42.31% of pts, mostly at the end of neoadjuvant therapy. In the regression model developed, weight was the only risk factor associated with cardiac events (p < 0.05). Nearly all were CTCAE grade 1-2, except for one case of heart failure. Conclusions: Given the similar effectiveness of the two chemotherapy regimens studied, acute toxicity and patient's profile should be taken into account to determine the best chemotherapy backbone in HER2+ eBC. Further follow-up is needed to determine the effect of long-term toxicity.