This ongoing RWE study on adjuvant trastuzumab-dkst for early-stage breast cancer (EBC) provides complementary insights to those offered by the HERITAGE study, which focused on metastatic HER2-positive BC. Our data feature a longer median follow-up period of over 30 months and include a diverse patient population in terms of age, ethnicity, reproductive status, comorbidity profiles, treatment regimens, and prior neoadjuvant therapies, enhancing the generalizability of the findings. Notably, 33.9% of our cohort consists of Pardo (mixed ethnic) individuals, underscoring the study’s representation of a group historically known to have poorer BC outcomes in Brazil [20].

The observed effectiveness, safety, and tolerability of trastuzumab-dkst in our study align with prior data. We reported a 100% OS rate and a 94.5% IDFS rate at 31.7 months of follow-up. The median IDFS was not reached due to low recurrence rates, with only three patients experiencing disease recurrence. These results resonate with the 2-year outcomes of the HERA study, a phase 3 open-label RCT that assessed reference trastuzumab (Herceptin®, Roche Pharmaceutical) as adjuvant treatment for HER2-positive EBC, reporting a 2-year OS rate of 92.4% and a disease-free survival (DFS) rate of 80.6% [22]. Although our findings suggest potentially better outcomes compared with the HERA study, it is important to emphasize that we are reporting preliminary results from an ongoing study. Additionally, our study’s IDFS endpoint specifically targets invasive malignancies, while the HERA study’s DFS endpoint includes new in situ BC [18, 22]. The HERA study’s extended follow-up of up to 11 years revealed a DFS rate of 69% and an OS rate of 79% [16]. Given the demonstrated therapeutic equivalence of trastuzumab-dkst [15], it is reasonable to anticipate that patients treated with this anti-HER2 biosimilar will experience comparable long-term benefits. Other studies with the reference trastuzumab, such as NSABP B-31, NCCTG N9831, and the BCIRG-006 trials, also demonstrated similar OS and DFS findings [23, 24].

Regarding distant recurrences, both our study and the HERA study reported low percentages at the 2-year follow-up mark. In our cohort, 5.1% (3 out of 59) of patients experienced a distant recurrence at intervals of 13.0, 15.1, and 23.9 months, respectively. The HERA study, in turn, observed a 5.0% distant recurrence rate within the first year, which increased to 9.0% by the end of the second year [15, 22].

The AEs observed with trastuzumab-dkst in our study align with those reported with other biosimilar or reference trastuzumab treatments [15, 21, 25, 26]. The incidence of serious AEs in this study (6.8%) was comparable to that reported in the HERA study (9.0%) [22]. However, for grade 3 or 4 AEs, the HERA study observed them in 18% of patients after 1 year and 22% after 2 years [18]. In contrast, in our study, only 3.4% of patients experienced grade 3 or 4 AEs during treatment, and the same percentage (3.4%) was observed post-treatment. Furthermore, 67.8% of AEs in our study were considered unrelated or likely unrelated to the treatment, with no patients withdrawing due to AEs. In the HERA trial, 11% of patients discontinued treatment due to AEs, including 5% due to cardiac events [26].

Previous studies have shown that 4.5% of patients treated with trastuzumab-dkst for metastatic BC experienced LVEF values below 50% at least once [21]. In our study, while 16.9% of patients experienced a decrease in LVEF of ≥ 10%, none had LVEF values drop below 50%. In the HERA study, 3% of patients presented a confirmed significant LVEF drop at the 2-year follow-up. Notably, during the extended evaluation period of up to 10 years, the HERA study did not observe new safety concerns, specifically no late cardiac issues, even as the patient cohort aged over a decade. Most of the cardiac events in the HERA study occurred during the treatment phase and were predominantly reversible [15, 16]. Therefore, our findings suggest that trastuzumab-dkst does not compromise cardiac function or the risk of cardiac events any differently than the reference trastuzumab.

The low incidence of acute infusional reactions in our study (3.38%) underscores trastuzumab-dkst’s tolerability in a real-world setting, compared with a 6.9% incidence in the phase 3 HERITAGE study [21].

Importantly, real-world data, such as that from our study, enriche our understanding of how medications perform outside the controlled conditions of clinical trials. It provides comprehensive insights into treatment effectiveness and clinical applicability across diverse patient populations, including those with conditions such as obesity and hypertension [27].

The evidence supports biosimilar monoclonal antibodies as cost-reducing options in oncology, potentially improving patient access to these important treatments without a detrimental effect on efficacy or safety [28]. However, challenges in biosimilar adoption remain, largely due to gaps in knowledge about biosimilar development, equivalence, regulatory requirements for their approval, and concerns related to their safety and efficacy [11]. By demonstrating these attributes, our findings contribute to increasing confidence in the use of biosimilars and add valuable evidence toward the broader acceptance and implementation of biosimilars in clinical settings, reinforcing their role in reducing oncology treatment costs while maintaining high standards of care [28].

This research builds upon the findings of the HERITAGE phase 3 trial, expanding trastuzumab-dkst therapeutic equivalence data beyond metastatic BC settings [14, 21].

Lastly, the recruitment from all five Brazilian regions enriches the diversity of our study population, broadening the applicability of our findings to various medical conditions and patient profiles. However, the limited sample size is a constraint of our analysis. Future analysis with our complete and larger cohort will further solidify these findings, thereby enhancing the generalizability of our conclusions.