Updated Phase 3 Results for CT-P6 Demonstrate the Biosimilar's Safety and Efficacy in Adjuvant Setting

Celltrion and Teva’s trastuzumab biosimilar, CT-P6 (Herzuma), was approved in 2018 for the treatment of HER2-positive breast cancer. Part of the data package that led to the approval of the drug, which is also approved in other regulatory territories including the European Union, was a phase 3 study in patients receiving neoadjuvant treatment for HER2-positive early breast cancer.

The results of the phase 3 study, reported elsewhere, showed that a similar proportion of patients achieved pathological complete response (PCR) with the biosimilar as with the reference trastuzumab, Herceptin. The proportion of patients who reported serious adverse events was also similar between groups.¹

This week, researchers reported updated results from a post hoc subgroup analysis from the adjuvant period of treatment; these results, say the authors, demonstrate that the biosimilar, used in the adjuvant setting, has comparable efficacy and safety to the reference at 1 year.²

In total, 254 patients who received the biosimilar and 262 patients who received the reference trastuzumab during the neoadjuvant period of the study entered the adjuvant treatment period. In the intent-to-treat (ITT) population, PCR rates were comparable between patients receiving the biosimilar and those receiving the reference, regardless of patients’ age, region of the world, or clinical disease stage. In total, 9 patients (3.3%) in the biosimilar group and 6 patients (2.2%) in the reference group in the ITT population had recurrent or progressive disease at 1 year.

During the adjuvant period, the relative dose intensity of trastuzumab was 98.5% (2.97) and 98.8% (2.27) in the biosimilar and reference groups, respectively. In total, 97% of patients receiving the biosimilar and 95.3% of patients receiving the reference experienced 1 or more treatment-emergent adverse event (AE). The most frequent AEs reported in the biosimilar group were rash, asthenia, and infusion-related reactions, whereas in the reference group, neutropenia, anemia, and alopecia were the most frequently reported.

With respect to serious AEs, 7.4% of patients in the biosimilar group and 11.9% of patients in the reference group experienced 1 or more serious AE. A similar proportion of patients in each arm (4.1% and 4.7%, respectively) experienced AEs leading to study discontinuation.

AEs due to heart failure were reported in 3.7% of patients in the biosimilar arm and 2.5% of patients in the reference arm. Among these patients, 16 (9 in the biosimilar arm and 6 in the reference arm) had a significant decrease in left ventricular ejection fraction.

According to the authors, these updated results demonstrate that the biosimilar is as effective as its reference in preventing disease progression in the adjuvant period and that the biosimilar has a similar safety profile—including a similar cardiotoxicity profile—to the reference.

References

1. Stebbing J, Baranau Y, Baryash V, et al. CT-P6 compared with reference trastuzumab for HER2-positive breast cancer: a randomised, double-blind, active-controlled, phase 3 equivalence trial. Lancet Oncol. 2017;18(7):917-928. doi: 10.1016/S1470-2045(17)30434-5.

2. Esteva FJ, Baranau YV, Baryash V, et al. Efficacy and safety of CT-P6 versus reference trastuzumab in HER2-positive early breast cancer: updated results of a randomised phase 3 trial [published online August 19, 2019]. Cancer Chemother Pharmacol. doi: 10.1007/s00280-019-03920-4.