Effect of trastuzumab interchangeability on efficacy and safety outcomes in women with early-stage HER2-positive breast cancer

Introduction: The insertion of biosimilars as a treatment option for complex diseases has brought a number of benefits, such as cost reduction and increased access to effective therapies. However, it has also raised important and challenging questions, both from a regulatory and clinical standpoint, such as interchangeability. Currently, there is a scarcity of clinical evidence, whether in randomized clinical trials or real-world studies, regarding the effect of this practice in patients with HER2-positive breast cancer.

Objective: To analyse the effect of interchangeability, involving multiple switches, on the effectiveness and safety of treatment for early-stage HER2-positive breast cancer.

Methods: This single-center retrospective cohort study included patients treated between 2018 and 2021. Sociodemographic, clinical, therapeutic, and safety data were collected. Logistic regression analyzed the association between interchangeability and pathological complete response (pCR). Disease-free survival (DFS) was assessed at 18 and 30 months using Kaplan-Meier and Log-rank tests between the interchangeability groups. Cox regression evaluated recurrence risk. Safety was assessed by adverse event (AE) occurrence, frequency, and severity.

Results: The study included 233 women, with 143 in the intervention group (interchangeability) and 90 in the control group (non-interchangeability). pCR rates were 31.5% (29/92) in the intervention group and 44.0% (62/141) in the control group (p = 0.059). Median DFS at 18 months was 17.6 months in the intervention group and 17.4 in the control group, with 6 and 8 recurrences (HR 0.46, 95% CI 0.16 – 1.35; p = 0.161), respectively. At 30 months, median DFS was 28.1 months in the intervention group and 27.3 months in the control group, with 17 and 14 recurrences (HR 0.98, 95% CI 0.58–1.67; p = 0.951), respectively. There was no statistically significant difference in the occurrence of AEs between the groups (p = 0.427). After initiating Trastuzumab, 115 (80.4%) patients in Group 1 and 79 (87.8%) in Group 2 experienced at least one AE. It was found that 34 (23.8%) women in Group 1 and 20 (22.2%) in Group 2 (p = 0.784) experienced severe AEs (grade 3 and 4). Cardiac events occurred in 18 (12.6%) patients in Group 1 and 6 (6.7%) in Group 2 (p = 0.148).

Conclusion: Interchangeability did not influence pCR, DFS or safety outcomes in the studied population. Future studies may complement and corroborate these findings.

Corresponding author: Mario Jorge Sobreira da Silva (e-mail: mjsobreira@yahoo.com.br).