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. (April 2022)

• Record Type: Journal Article
• Authors: Bernat-Peguera, Adrià; Trigueros, Macedonia; Ferrando-Díez, Angélica; Ibáñez, Cristina; Bystrup, Sara; Martínez-Cardús, Anna; Margelí, Mireia; Martínez-Balibrea, Eva
• Is Part Of: Breast. Volume 62(2022)Supplement 1
• Page Start: 1
• Page End: 9
• Publication Date: 2022-04
• Subjects: HER2-Positive breast cancer -- Biosimilar -- Trastuzumab -- Pertuzumab -- Taxanes -- CT-P6; RTZ reference trastuzumab -- ICO Institut Català d'Oncologia (Catalan Institute of Oncology); Breast -- Diseases -- Periodicals; Breast -- Tumors -- Periodicals; Breast -- Periodicals; Electronic journals; Periodicals; 616
• DOI: 10.1016/j.breast.2022.01.007
• Languages: English
• ISSNs: 0960-9776

Abstract

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. Highlights: CT-P6 or RTZ + pertuzumab + paclitaxel are equivalent treatments in HER2+ BC cells. Equivalent efficacy and safety of CT-P6 or RTZ in HER2+ EBC patients. Using CT-P6 represents important savings for the health system. HER2 low BC is a promising scenario for new anti-HER2 therapies.