The Impact of Trastuzumab Administration Patterns on the Long-Term Clinical Outcomes of Patients with Non-Metastatic Breast Cancer in a Resource-Limited Setting

Abstract

Background: Administration of trastuzumab (TRA) in resource-limited settings (RLS) is associated with significant deviations from per-label recommendations such as fixed-dose instead of weight-based, interruptions, and a reduced number of cycles. The impact of these deviations on the clinical outcomes of HER2-positive non-metastatic breast cancer is unclear. Methods: We retrospectively reviewed the records of patients with operable HER2-positive breast cancer treated at our center from 2013 to 2018 for TRA dose deviations. The standard protocol for TRA administration includes a one-year course of TRA with one intravenous dose every three weeks for 17 cycles. We assessed the number of cycles, underdosing based on body weight calculation, and low relative dose intensity (RDI). Cox regression analysis was used to identify predictors of survival and was adjusted for baseline clinical variables. Results: This analysis included 208 patients with a median age of 45 years. A total of 175 (84%) patients showed at least one per label deviation. Fifty-four patients (26%) were underdosed with a mean maintenance dose defect of 54 ±107 mg, 64 (31%) received a reduced number of courses (≤ 9 cycles), and 103 patients (49.5%) received TRA at low RDI. Reduced number of cycles was the only factor associated with a worse hazard of recurrence-free survival and overall survival (HR: 2.25, 95% CI: 1.35-3.75, adjusted p =0.002) and (HR: 2.48, 95% CI: 1.36-4.52, adjusted p =0.003), respectively. Conclusion: In our cohort, not all the deviations had adverse impacts on clinical outcomes. Only a reduced number of cycles was associated with a worse recurrence-free and overall survival hazard. Improving access to anti-HER2 therapies in RLS is crucial. Ensuring the full course of TRA in RLS is needed.