2026 Southeastern Residency Conference

Purpose: Trastuzumab, with or without pertuzumab, is used in the treatment of human epidermal growth factor receptor 2-positive (HER2+) metastatic breast cancer. Both of these monoclonal antibodies require loading doses at treatment initiation and after specified dose delays per their package inserts. This dosing rationale is based on pharmacokinetic studies in patients with solid tumors, which evaluated the time required for serum drug levels to return to steady state after dose interruptions when a patient is not reloaded. Despite this guidance, it is suspected that not all providers prescribe reloading doses as recommended after delays in treatment. To our knowledge, there are no published studies investigating the real-world patient outcomes of not reloading these medications.

Methods: This IRB-approved, retrospective cohort analysis was designed to evaluate the incidence of reloading pertuzumab- and trastuzumab-containing products and their impact on disease progression. Patients were categorized into two groups: those who were appropriately loaded after a dose delay, as defined in the respective medication package inserts. and those who were not. Patients were randomized at a 1:1 ratio. The primary endpoint was to determine which patients were appropriately loaded compared to those who were not. Secondary endpoints included median time of dose delay, reason for dose delay, prescriber-dependent reloading dose practices, and time to disease progression. Descriptive statistics were used to define which patients were appropriately loaded compared to those who were not, the reason for dose delay, and which providers did or did not reload appropriately. A Kruskal-Wallis H test was used to determine the median time of dose delay. A Mann-Whitney U test was used to determine the time to disease progression.

Results: The study included a total of 29 patients. Of the 29 patients, seven patients (24.1%) were reloaded appropriately, and 22 patients (75.9%) were not reloaded appropriately after treatment delay. The median time of dose delay was 21 days (IQR 21-40 days). Many dose delays were not adequately documented with a reason for the delay (31%). The most commonly documented reason for dose delay was hospitalization (27%). When assessing the effect this had on disease progression, patients who were reloaded had a median time to progression of 1461 days (IQR 307-3302), and patients who were not reloaded had a median time to progression of 686 days (IQR 257-967). This difference was not statistically significant (p = 0.36).

Conclusion: This study showed the median time to progression of disease was longer in patients who were properly reloaded after a dose delay. However, this was not statistically significant and did contain a potential outlier in the appropriately reloaded group. The small sample size was a limitation, and therefore, the study was unable to meet power. Future studies are warranted to further assess the impact that reloading may have on disease progression with a larger patient population and potentially including patients with additional disease states that include HER2+ directed therapy.
  

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