Abstract P6-17-03: 24 months results from a double-blind, randomized phase III trial comparing the efficacy and safety of neoadjuvant then adjuvant trastuzumab and its biosimilar candidate CT-P6 in HER2 positive early breast cancer (EBC)
Authors: Esteva FJ , Lee S , Yu S , Kim M , Kim N , Stebbing J 
Published: May 2019

Abstract
Background CT-P6 is a proposed biosimilar to reference trastuzumab (RTZ). A double-blind, randomized, phase III trial showed similar efficacy and safety for CT-P6 and RTZ in HER2 positive EBC (NCT02162667). The primary endpoint, pathological complete response rate was within the predefined margin to demonstrate similarity (Lancet Oncol 2017). Safety and efficacy at 1 year (ESMO 2017), and cardiac toxicity at a median of 19 months (SABCS 2017) were similar between the two treatment groups. Here we report updated disease-free survival (DFS), overall survival (OS) and cardiac toxicity data with a median follow-up of 2 years.
Methods A total of 549 patients with HER2 positive EBC were randomized to receive CT-P6 (n=271) or RTZ (n=278) in combination with docetaxel (Cycles 1-4) and 5-fluorouracil, epirubicin and cyclophosphamide (Cycles 5-8). CT-P6 or RTZ was administered at 8 mg/kg (Cycle 1 only) followed by 6 mg/kg every 3 weeks. After surgery, patients received CT-P6 or RTZ monotherapy then entered the follow-up period up to 3 year of last patient enrollment. Time to event analyses were performed using Cox regression and Kaplan-Meier methods.
Results A total of 528 patients (259/271 in CT-P6 and 269/278 in RTZ) entered the follow-up period after completing therapy. The median follow-up duration was over 27 months. The number of DFS events (32 [12.4%] in CT-P6 and 26 [10.0%] in RTZ) and OS events (14 [5.2%] in CT-P6 and 12 [4.3%] in RTZ) were comparable in the ITT set. Additionally, DFS and OS were similar between CT-P6 group and RTZ group in both the per-protocol set (PPS) and the ITT set. In the ITT set, the proportion of 2-year DFS (95% CI) was 86% (80% – 90%) in CT-P6 and 90% (85% – 93%) in RTZ. The proportion of 2-year OS was 97% (93% – 98%) in CT-P6 and 98% (96% – 99%) in RTZ. Median DFS and OS have not been reached. After 1-year treatment, no new cases of heart failure were reported during the follow-up period. Left ventricular ejection fraction (LVEF) was similar in both groups (mean LVEF, more than 60%).
Table 1.Summary of Long Term Efficacy Endpoints PPSITT set CT-P6 (n=248)Reference Trastuzumab (n=256)CT-P6 (n=258)Reference Trastuzumab (n=261)Proportion of DFS1 year (95% CI)0.95 (0.91 – 0.97)0.96 (0.93 – 0.98)0.95 (0.91 – 0.97)0.96 (0.93 – 0.98)2 years (95% CI)0.86 (0.80 – 0.90)0.90 (0.85 – 0.93)0.86 (0.80 – 0.90)0.90 (0.85 – 0.93)p-value0.33240.3085 CT-P6 (n=248)Reference Trastuzumab (n=256)CT-P6 (n=271)Reference Trastuzumab (n=278)Proportion of OS1 year (95% CI)1.00 (1.00 – 1.00)1.00 (0.97 – 1.00)0.99 (0.97 – 1.00)0.99 (0.97 – 1.00)2 year (95% CI)0.97 (0.94 – 0.99)0.98 (0.96 – 0.99)0.97 (0.93 – 0.98)0.98 (0.96 – 0.99)3 year (95% CI)0.94 (0.88 – 0.97)0.93 (0.86 – 0.96)0.92 (0.86 – 0.96)0.93 (0.87 – 0.96)p-value0.93290.5057
Conclusions The efficacy and cardiac toxicity profile between CT-P6 and RTZ in EBC patients were consistent with published data. Time to event analyses as secondary efficacy endpoints supported the similarity for the two study drugs. CT-P6 was consistently well tolerated with a similar cardiotoxicity profile to that of RTZ through long duration of follow-up.
Citation Format: Esteva FJ, Lee S, Yu S, Kim M, Kim N, Stebbing J. 24 months results from a double-blind, randomized phase III trial comparing the efficacy and safety of neoadjuvant then adjuvant trastuzumab and its biosimilar candidate CT-P6 in HER2 positive early breast cancer (EBC) [abstract]. In: Proceedings of the 2018 San Antonio Breast Cancer Symposium; 2018 Dec 4-8; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2019;79(4 Suppl):Abstract nr P6-17-03.