LA-EP2006 as Effective, Safe as Reference Pegfilgrastim in Asian Patients With Breast Cancer

Recombinant human granulocyte colony-stimulating factor (G-CSF), filgrastim, and its long-acting pegylated form, pegfilgrastim, are widely used to reduce the risk of chemotherapy-induced neutropenia, but to date, no pegfilgrastim biosimilar has been approved in highly regulated markets such as Europe, Japan, and the United States.

LA-EP2006 (Sandoz/Novartis), a proposed biosimilar to pegfilgrastim (Neulasta, Amgen), showed similar clinical efficacy and safety compared with reference pegfilgrastim in a recent analysis of studies in patients with breast cancer (all Asian) who were enrolled in 2 phase 3 confirmatory studies. Nadia Harbeck, MD, PhD, and colleagues published the results of an exploratory comparison of data from these studies in Future Oncology. The study was supported by Sandoz, which plans to resubmit its application for approval of LA-EP2006 to the FDA in 2018 following receipt of a complete response letter to the initial filing.

The researchers studied Asian patients in particular because the incidence of breast cancer in Asian populations is rapidly increasing. Though the overall incidence of breast cancer in Asia remains lower than in Western countries, the mortality-to-incidence ratio for breast cancer is higher in Asia than it is in the United States. “Patients in Asia are more likely to die from breast cancer than patients in the USA,” they note, and this fact highlights a need for appropriate treatment and supportive care in Asian patients with breast cancer.

Furthermore, while G-CSF has been extensively studied in other patient populations, there is a lack of clinical recommendations for the use of G-CSF in Asian patients with breast cancer undergoing TAC (docetaxel, doxorubicin, and cyclophosphamide) chemotherapy, and only limited data from randomized controlled trials of G-CSF in Asian patients, particularly in those with breast cancer. Thus, the researchers performed a subgroup analysis of patients of Asian ethnicity who were enrolled in the PROTECT-1 and -2 trials of LA-EP2006 compared with reference pegfilgrastim in patients with breast cancer receiving TAC chemotherapy.

One hundred and seventy-four patients were randomized to receive LA-EP2006 with TAC chemotherapy (n = 90) or reference pegfilgrastim with TAC chemotherapy (n = 84) for up to 6 cycles. The primary study endpoint was the duration (in days) of severe neutropenia during cycle 1 (number of consecutive days with absolute neutrophil count less than 0.5 x 10⁹/L) with equivalence confirmed if 95% confidence intervals (CIs) were within a ±1-day margin. The researchers report that the mean duration of severe neutropenia (days) in cycle 1 was 1.36± 0.98 for the LA-EP2006 arm versus 1.35±1.06 for the reference pegfilrastim arm. The difference was 0.01 days, with a 95% CI (range, -0.30 to 0.32), which indicated equivalence. Thus, the researchers concluded that LA-EP2006 showed similar clinical efficacy and safety compared with reference pegfilgrastim.

Treatment-emergent adverse events (TEAEs) were similar across the groups—TEAEs were reported in 96.7% of the LA-EP2006 group and 97.6% of the reference pegfilgrastim group. TEAEs with a suspected relationship to the study drug were reported in 27.8% of patients in the biosimilar group and 21.4% of the group receiving the reference drug.

The most frequently reported TEAEs with a suspected relationship to the study drug were of 2 system organ classes: blood and lymphatic system disorders (13.3%, biosimilar; 7.1%, reference), and musculoskeletal and connective tissue disorders (11.1%, biosimilar; 6.1%, reference). Serious TEAEs were reported in 31.1% of patients in the LA-EP2006 group and 32.1% of patients receiving the reference drug. Serious TEAEs considered related to study drug were reported in 5.6% of patients in the LA-EP2006 group and 1.2% of patients in the reference group. Six patients died during the studies, 4 of whom were in the biosimilar group and 2 in the reference group. None of the deaths were considered related to biosimilar or reference pegfilgrastim.

Immunogenicity results were similar across the 2 studies, and no post-dose treatment-related binding and neutralizing antibodies against pegfilgrastim, filgrastim, or PEG were detected in any of the patients at any time.

The researchers said that the burden that cancer presents on healthcare systems grants a rationale for the development of biosimilars, which have the potential to increase access to important and expensive cancer treatments. “The need to develop treatment and prevention strategies in countries with limited resources is urgent, and biosimilars could help provide a means to release funding for other treatments, as well as increasing access to supportive care,” they said.