Abstract P5-20-14: Cardiotoxicity in 1 year of treatment with reference trastuzumab and its biosimilar candidate CT-P6 in HER2 positive early stage breast cancer (EBC) patients
Authors: Esteva FJ , Chung HC , Royce ME , Lee SY , Lee SJ , Stebbing J 
Published: February 2018

Abstract
Background CT-P6 is a proposed biosimilar to reference trastuzumab. This trial (NCT02162667) evaluated the similarity of CT-P6 and reference trastuzumab for both efficacy and safety in HER2 positive EBC patients. The primary endpoint, pathological complete response (pCR) rate was entirely within the pre-defined equivalence margin (Stebbing et al., Lancet Oncology 2017). Efficacy and safety were similar between the two treatment groups. We aimed to investigate the cardiotoxicity in the 1 year treatment and follow-up period.
Methods A total of 549 patients with HER2 positive EBC were randomized to receive CT-P6 (n=271) or reference trastuzumab (n=278) in combination with docetaxel (Cycles 1-4) and 5-fluorouracil, epirubicin and cyclophosphamide (FEC, Cycles 5-8) in the neoadjuvant setting. CT-P6 or reference trastuzumab was administered at 8 mg/kg (Cycle 1 only) followed by 6 mg/kg every 3 weeks. After surgery, patients received monotherapy of CT-P6 or reference trastuzumab up to 10 cycles in the adjuvant setting. Left ventricular ejection fraction (LVEF) was evaluated by ECHO or MUGA at baseline, every 3 or 4 cycles during treatment and every 6 months thereafter. If LVEF decreased by ≥10 points from baseline and &lt;50%, a reassessment was performed within 3 weeks and the patient was withdrawn from the study treatment if the cardiac toxicity was confirmed.
Results Median follow-up period was 19 months. In total, 96% of patients completed 8 cycles of taxane and anthracycline combination therapy during the neoadjuvant period and 90% of patients in each group received 1-year treatment of CT-P6 or reference trastuzumab.
The relative dose intensity of study drug was similar, indicating good tolerability of CT-P6 and reference trastuzumab (97.5% and 97.3% during the neoadjuvant period; 98.5% and 98.8% during the adjuvant period). Docetaxel and FEC combination therapies were administered approximately 96% of dose intensity in the two groups.
All patients had normal LVEF (≥55%) at baseline. Mean LVEF value was maintained more than 60% during 1-year treatment and follow-up period. Heart failure cases with LVEF decrease (≥10 points from baseline and &lt;50%) were reported to be similar between two groups. Three patients in each group were withdrawn due to LVEF decrease. Adverse events of cardiac disorders were reported to be similar between two groups. All cases were mild or moderate except two cases.
Table 1. Summary of heart failure with LVEF decrease and cardiotoxicity CT-P6 (N=271)Reference Trastuzumab (N=278)LVEF decrease ≥ 10 points and below 50%9 (3.3%)7 (2.5%)- Asymptomatic9 (3.3%)6 (2.1%)- Symptomatic01 (0.4%)- Confirmed2 (0.7%)4 (1.4%)- Withdrawn3 (1.1%)3 (1.1%)Cardiac disorder by AEs31 (11.4%)38 (13.7%)- Grade 1 to 230 (11.0%)37 (13.3%)- Grade 3 to 51 (0.4%)11 (0.4%)21 Grade 3 of Adams-Strokes syndrome occurring 5 months after the completion of 1-year treatment; 2 Grade 5 of acute myocardial infarction occurring 10 days after Cycle 1 of the neoadjuvant therapy
Conclusions Combination therapy of CT-P6 with taxane/anthracycline and monotherapy of CT-P6 over 1 year period were well tolerated and cardiotoxicity was similar to reference trastuzumab.
Citation Format: Esteva FJ, Chung HC, Royce ME, Lee SY, Lee SJ, Stebbing J. Cardiotoxicity in 1 year of treatment with reference trastuzumab and its biosimilar candidate CT-P6 in HER2 positive early stage breast cancer (EBC) patients [abstract]. In: Proceedings of the 2017 San Antonio Breast Cancer Symposium; 2017 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2018;78(4 Suppl):Abstract nr P5-20-14.