The results from a retrospective study of Egyptian patients receiving adjuvant or neoadjuvant trastuzumab for early-stage HER2-positive breast cancer showed that many patients receiving fixed doses of trastuzumab were underdosed when patient body weight was considered. This study was published in the Journal of Global Health.1
The results from the pivotal phase 3 HERceptin Adjuvant (HERA) trial (ClinicalTrial.gov Identifier: NCT00045032) conducted in patients with early-stage breast cancer showed that trastuzumab therapy administered intravenously (IV) as a loading dose of 8 mg/kg on day 1 followed by a maintenance dose of 6 mg/kg IV 3 weeks later and thereafter every 3 weeks was as effective in prolonging disease-free and overall survival as 2 years of trastuzumab therapy administered using the same dose and schedule.2
However, in many low- and middle-income countries, either the dose of trastuzumab is fixed (ie, independent of body weight) or the duration of trastuzumab therapy is shortened to less than 1 year.
This retrospective study investigated the patient- and treatment-related characteristics of 113 Egyptian patients with early-stage breast cancer who received at least 1 fixed dose (440 mg every 3 weeks) of trastuzumab therapy in the adjuvant or neoadjuvant setting.
In this patient cohort, the median number of trastuzumab cycles was 9, and the mean duration of trastuzumab treatment was 250.6 days. Treatment interruptions occurred in 77% of patients due to drug shortages, or reimbursement or safety issues. The mean body weight and mean body mass index (BMI) of the patients were 85.44 kg and 34.43 kg/m2, respectively.
Based on these measurements, the study authors determined that the rates of underloaded and undermaintained patients (defined as those who needed 500 mg as their loading and maintenance doses, respectively) were 68% and 37.2%, respectively.
The authors proposed a 3-part approach to investigating the impact of fixed-dose trastuzumab in the setting of early-breast cancer:
- Making measurements of trastuzumab-related pharmacokinetic parameters in patients with high or low BMI
- Performing comparisons of surrogate clinical end points (ie, pathologic complete response and response rates) across different BMI categories in patients who receive either fixed-dose or weight-based trastuzumab dosing to develop a pharmacokinetic model for the optimal fixed dose of trastuzumab based on safety and minimal variability according to body weight
- Conducting a small prospective pharmacokinetic-oriented study to validate suggested fixed dose.
“Adopting a fixed 440-mg one-vial dose for every patient is a questionable approach that needs additional assessment. Investing in clinical studies with PK surrogate end points is important in low-resource settings,” the authors concluded.
- Kassem L, Shohdy KS, Abdel-Azeez AM, Attia H. Is the fixed-dose intravenous trastuzumab policy warranted in limited-resource settings? J Glob Oncol. 2019;5:1-3.
- Goldhirsch A, Gelber RD, Piccart-Gebhart MJ, et al. 2 years versus 1 year of adjuvant trastuzumab for HER2-positive breast cancer (HERA): an open-label, randomised controlled trial. Lancet. 2013;382:1021-1028