Investigators in Brazil are seeking to explore the efficacy and safety of adjuvant biosimilar trastuzumab in a real-world study of patients with early HER2-positive breast cancer. In 2019, biosimilar trastuzumab became the first biosimilar approved in Brazil for the treatment of patients with HER2-positive breast cancer. In developing countries, cost is a barrier to treatment. A biosimilar trastuzumab may present an opportunity for cost savings and thereby lead to improved access for patients requiring therapy for HER2-positive disease.
Leandro Alves, PhD
Debora Gagliato, MD
Leonardo F. Orlandini, MD
Leandro Alves, PhD, of Libbs Pharmaceutical, and Debora Gagliato, MD, of the Hospital Beneficência Portuguesa de São Paulo in Brazil, presented details of one ongoing study at the 2019 San Antonio Breast Cancer Symposium.1
In a second study, Leonardo F. Orlandini, MD, of the Ribeirão Preto Medical School at the University of São Paulo in Ribeirão Preto, Brazil, investigated the use of adjuvant trastuzumab in a real-world population-based cohort and compared the group’s findings to those reported in a phase III clinical trial.2,3
Prospective Real-World Study
Dr. Alves and coinvestigators are performing a national, multicenter, observational, prospective, real-world study in a number of institutions in Brazil, including a total of 170 patients. Patients with early-stage HER2-positive breast cancer who received at least one dose of adjuvant biosimilar trastuzumab will be followed for 5 years unless they experience disease recurrence or death. Investigators will monitor safety and efficacy including progression-free survival at several intervals.
The investigators referred to the Heritage study showing biosimilarity between the reference trastuzumab and biosimilar trastuzumab and believe they will find the same safety and efficacy profile.
Rugo et al reported the results of a phase III equivalence trial—the Heritage study—and demonstrated that treatment with the trastuzumab biosimilar (trastuzumab-dkst) was equivalent to trastuzumab, both in combination with a taxane, in terms of overall response rates at 24 weeks in patients with previously untreated metastatic HER2-positive breast cancer.1 At 48 weeks, there were no differences in time to disease progression or progression-free or overall survival. Additionally, there were no differences in adverse events. The development of a biosimilar for treatment in this setting could mean lower health-care costs for society overall, as well as greater access to an important drug for a larger breast cancer population across the globe.
1. Rugo H, Barve A, Waller CF, et al: Effect of a proposed trastuzumab biosimilar compared with trastuzumab on overall response rate in patients with ERBB2 (HER2)–positive metastatic breast cancer. JAMA 317:37-47, 2017.
In a second study, investigators evaluated the benefit of adjuvant trastuzumab in a cohort of patients with HER2-positive breast cancer treated in a public hospital and compared their findings to data from a similar group of patients in a phase III clinical trial.2,3 Data from patients treated in the public hospital were retrospectively gathered from medical records of 410 patients with HER2-positive disease. Among these patients, 43% (173) received trastuzumab plus chemotherapy. A total of 232 patients (57%) received chemotherapy only.
According to the investigators, these retrospective data showed that the patients in Brazil who received trastuzumab plus chemotherapy experienced significantly improved disease-specific survival compared to those patients who received chemotherapy alone (P < .0001). In comparing their data to that reported in a phase III clinical trial by Slamon et al,3 they also found an increase in disease-specific survival for patients receiving trastuzumab.
The investigators reported that cost could be a barrier to receiving adjuvant trastuzumab in Brazil, and they noted that until 2012, patients received the drug only after legal litigation. Between 2013 and 2018, the Brazilian government purchased trastuzumab centrally. They acknowledged that the arrival of biosimilar trastuzumab to Brazil in 2019 could yield an improved cost-benefit ratio.
The authors concluded that “In this study we showed a HER2-positive breast cancer population from an upper-middle–income country with a greater benefit for adjuvant trastuzumab.… Considering that the real-world population may present a higher incidence of advanced cases compared to populations of clinical trials, the clinical benefit of a drug may be even greater than estimated.” Further, they noted that “local estimation of effectiveness may result in an even greater cost-benefit than that found in clinical trials, contributing to public health planning.”
DISCLOSURE: Dr. Alves is a salaried employee of Libbs Pharmaceutical. Dr. Gagliato has performed contracted research for Libbs Pharmaceutical. Dr. Orlandini reported no conflicts of interest.
1. Alves L, Gagliato D, de Paula M, et al: A prospective real-world study to evaluate the efficacy and safety of adjuvant biosimilar trastuzumab in the treatment of HER2-positive breast cancer. 2019 San Antonio Breast Cancer Symposium. Abstract OT2-01-05. Presented December 12, 2019.
2. Orlandini LF, Pimentel FF, Carrara HH, et al: Adjuvant trastuzumab effectiveness in a cohort of HER2-positive breast cancer Brazilian patients treated in a public hospital. 2019 San Antonio Breast Cancer Symposium. Abstract P2-08-22. Presented December 12, 2019.
3. Slamon D, Eiermann W, Robert N, et al: Adjuvant trastuzumab in HER2-positive breast cancer. N Engl J Med 365:1273-1283, 2011.