Efficacy of CT-P6 (trastuzumab biosimilar) versus reference trastuzumab in combination with pertuzumab in HER2-positive early-stage breast cancer: Preclinical and real-life clinical data

Abstract

After the expiration of trastuzumab data exclusivity, biosimilar drugs were approved by regulatory agencies; among them, CT-P6 which was approved for the treatment of HER2-positive early- and advanced-breast cancer (BC) in 2018. Yet, reference trastuzumab (RTZ) is often combined with pertuzumab in early BC (EBC) patients treated with chemotherapy as it significantly improves the pathological complete response rate. Unfortunately, scarce preclinical and clinical data exists about the combination of CT-P6, pertuzumab and chemotherapy. Therefore, our aim was to study in vitro and in a retrospective cohort of EBC patients, whether CT-P6 was equivalent to RTZ when combined with pertuzumab with or without taxanes. In BT-474 and SKBR3 HER2+ cells we found that CT-P6 alone or in combination with pertuzumab had the same negative effect on cell proliferation, colony formation and HER2 downregulation as well as downstream activation, as RTZ. Adding paclitaxel to these treatments increased their effectivity to a similar extent. In HER2 1+ neuregulin-secreting MB-MDA-175 cells, combinations of CT-P6 or RTZ with pertuzumab were also effective, and mainly dependent on HER3:HER2 heterodimerization. In a retrospective cohort of 44 EBC HER2+ patients treated with neoadjuvant RTZ or CT-P6 in combination with pertuzumab and chemotherapy, we found no differences in efficacy or in adverse events. Moreover, the costs of CT-P6-based treatments were reduced by 1474.07 €/patient. All together we provide pre-clinical and clinical evidence of the equivalence of CT-P6 in combination with pertuzumab and chemotherapy and suggest studying these combinations also in HER2 low/negative BC patients.

Clinical Benefit, Price, and Uptake for Cancer Biosimilars vs Reference Drugs in China

“…eFigure 2 in Supplement 1 shows the process of study screening. Of the 1195 records sourced from the database and manually searched, 49 studies met the inclusion criteria, including 39 RCTs and 10 cohort studies …”

“…were high risk 72,76,77,79 and 6 (60.0%) were low risk. 71,[73][74][75]78,80 Comparison With Pivotal Trials Among the 4 Agencies…”

“…[32][33][34][35][36][37][38][39][40][41][42][43][47][48][49][50][51][52][53][54][55]58,[62][63][64][65][66][67] Table 1 and eTable 7 in Supplement 1 summarize the characteristics of the 10 cohort studies with a total of 1998 patients. [71][72][73][74][75][76][77][78][79][80] Of the 10 cohort studies, 1 (10.0%) was of a bevacizumab biosimilar, 71 3 (30.0%) were of rituximab biosimilars, [72][73][74] and 6 (60.0%) were of trastuzumab biosimilars. [75][76][77][78][79][80] All cohort study designs were retrospective.…”

“…Five cohort studies of trastuzumab biosimilars were for breast cancer, 75,76,[78][79][80] while 1 was for gastric cancer. 77 There were no significant differences in effectiveness and safety outcomes between the rituximab biosimilar group and the reference group (eTable 13 in Supplement 1).…”

Six-Year Survival Outcomes for Patients with HER2-Positive Early Breast Cancer Treated with CT-P6 or Reference Trastuzumab: Observational Follow-Up Study of a Phase 3 Randomised Controlled Trial

“…Indeed, a budget impact analysis conducted across France, Germany, Italy, Spain and the UK estimated 5-year savings of €19-172 million with the uptake of biosimilars to reference trastuzumab [23], whereas a larger analysis of CT-P6 for the treatment of breast cancer and gastric cancer conducted across 28 European countries estimated 5-year savings of €0.91-2.27 billion [24]. Real-world findings concur: in a retrospective analysis of 44 patients with HER2-positive early breast cancer, neoadjuvant CT-P6-based treatment was associated with cost savings of €1,474 per patient versus reference trastuzumab, with no difference in efficacy [25]. Lower cost, evidence of long-term clinical equivalence to reference products, and improved education and training are all factors that should influence the future adoption of anti-HER2 biosimilars [26,27].…”