Efficacy and safety of neoadjuvant double anti-Her2 blockade combined with anthracycline-free chemotherapy in locally advanced breast cancer.

Abstract

e12612 Background: Double anti-Her2 blockade combined with chemotherapy (CT) is a standard regimen in Her2 positive locally advanced breast cancer (LABC) with a high risk of relapse. TCHP provides more anti-Her2 treatment, better pathological complete response (pCR) rates and less cardiotoxicity. However, it is not a very widespread option due to the risk of toxicity. Our group shows a manageable toxicity profile by adding G-CSF as primary prohylaxis. Methods: We describe our experience with neoadjuvant TCHP and pegfilgrastim combination between years 2017-2023. Efficacy and safety were analyzed and compared with other schemes accepted by clinical guidelines. Results: 62 patients, median age 48 years; 61.3% were premenopausal; 54.8% were stage II at diagnosis and 45.2% were stage III; 67.7% had N+; 62.9% had RH-. A total of six cycles were completed in 85.5%; 8 patients discontinued treatment due to toxicity. The most frequent adverse events were hematological (grade 3-4 in 8.1%) and digestive (grade 3-4 in 19.4%). No cardiac event was reported. 6.5% were hospitalized due to toxicity (3.2% febrile neutropenia). Dose reduction was needed in 43.5%. Clinical response occurred in 98.4% and radiological response in 87.1% (complete in 38.7%). pCR (ypT0/isN0) was obtained in 67.7% (66.7% in N+; 77.4% in RH-). Up to now, 4 patients have relapsed (3 of them had pRC) and 3 have died. After median 24.5 months of follow-up, the median relapse-free and overall survival by Kapplan-Meier have not been reached. Cox regression shows that getting rPC does not impact survival. The Odds Ratio shows a higher proportion of obtaining pRC in the RH- and N+ subgroups, but without statistically significant differences. Conclusions: Our data based on combination of TCHP and pegfilgrastim shows considerable efficacy with an acceptable toxicity profile. The main advantage is the intensification of double lock dose, without anti Her2 window period, avoiding the addition of anthracyclines and, therefore, cardiac toxicity. pRC and toxicity profile results were better than other regimen proposed in other studies. Our data shows that pRC has no impact on survival. We assume a favorable association between pRC and N+ and HR-, although not statistically significant, probably due to the small amount of patients. Based on these favorable results, we believe that the priority use of TCHP-GCSF should be considered in the neoadjuvant treatment of Her2+ LABC. [Table: see text]