Abstract P4-21-19: Systematic review of clinical trials for monoclonal antibody biosimilars in HER2-positive breast cancer
Authors: Jacobs I , Isakov L , Vana AM , Coiro J , Zacharchuk C , Ewesuedo R 
Published: March 2017

Abstract
Background: A number of proposed trastuzumab (TRAS) biosimilars are now in development for HER2-overexpressing breast cancer treatment. The purpose of this study was to systematically collate all published clinical data to assess the weight of available evidence for TRAS biosimilars in HER2-positive (+) breast cancer (BC), and to identify additional studies, not captured in the scientific literature, to support informed decision-making by healthcare stakeholders, as well as to raise awareness of ongoing developments within the field. Methods: MEDLINE®, Embase® and ISI Web of Science® were searched from inception to Sept 3, 2015. Conference proceedings (n=17) were searched from 2012 to Jul 31, 2015. Studies disclosing potential use of proposed biosimilars in the treatment of HER2+ BC were screened and categorized by originator and study type (English language only). To assess data strength and validity, risk of bias assessments were conducted. The ClinicalTrials.gov (CT.gov) registry was searched to identify any planned/ongoing/complete biosimilar trials in HER2+ BC. Results: On the analysis cut-off date, a total of 7 clinical studies (12 publications) were identified for proposed biosimilars of TRAS. The biosimilars identified for TRAS with published clinical data were BCD-022, CT-P6, FTMB and PF-05280014. For BCD-022, a pharmacokinetics (PK)/safety study in HER2+ BC (N=46) evaluating BCD-022 compared to TRAS, demonstrated equivalence between the two treatments. A PK/safety study (N=174) and comparative safety/efficacy study (N=475) of CT-P6 in HER2+ BC patients both provided evidence of PK equivalence, safety, and efficacy of the proposed biosimilar in this patient population. Bioequivalence of FTMB (versus TRAS) was also reported based on the results of a PK/safety study (N=118) in healthy subjects. For PF-05280014, a PK/safety study (N=105) in healthy volunteers demonstrated equivalence with TRAS. One published comparative safety/efficacy study protocol for PF-05280014 versus TRAS was identified for first-line treatment of patients with HER2+ BC (estimated [E]:N=690), and a second PK/efficacy/safety protocol for neoadjuvant BC treatment (E:N=220) was also published. A number of other planned studies were identified in CT.gov. These included 4 comparative safety/efficacy studies in HER2+ BC evaluating ABP 980 (E:N=808), CT-P6 (N=383/N=532), SB3 (E:N=806) and 2 PK/safety studies (BCD-022 [E:N=206], CT-P6 [E:N=174]) in women with BC. Two studies investigating PK and safety in healthy volunteers were also identified (PF-05280014 [E:N=162], SB3 [E:N=109]). Conclusions: This systematic review provides an unbiased synthesis of available evidence for proposed TRAS biosimilars in HER2+ BC, including data to support clinical similarity. The available clinical data for the 4 proposed biosimilars (BCD-022, CT-P6, FTMB and PF-05280014) investigated in a total of 918 healthy subjects or patients indicated highly comparable PK, safety, or efficacy profiles, versus TRAS. Additional data are required to fully evaluate the clinical similarity for proposed TRAS biosimilars, and the completion of several ongoing comparative trials are expected to provide further assurance of safety and efficacy in specific patient populations.
Citation Format: Jacobs I, Isakov L, Vana AM, Coiro J, Zacharchuk C, Ewesuedo R. Systematic review of clinical trials for monoclonal antibody biosimilars in HER2-positive breast cancer [abstract]. In: Proceedings of the 2016 San Antonio Breast Cancer Symposium; 2016 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2017;77(4 Suppl):Abstract nr P4-21-19.