Abstract P1-18-08: Trazimera (a trastuzumab biosimilar) in HER2-positive metastatic breast cancer: Long-term safety and overall survival data
Authors: Li Rubi K , Lipatov Oleg , Adamchuk Hryhoriy , Vladimirov Vladimir , Yanez Eduardo , Banchero Patricia , Freyman Amy , Hilton Fiona , Thiele Alexandra , Vana Alicia 
Published: March 2020

Abstract
Background: Trazimera™ (PF-05280014) is a trastuzumab biosimilar. This multinational, randomized, double-blind, parallel-group study (NCT01989676) compared Trazimera with reference trastuzumab (Herceptin®) sourced from the EU (Herceptin-EU), each plus paclitaxel, in the first-line treatment of HER2-positive metastatic breast cancer (MBC). Equivalence between the two groups was previously demonstrated for the primary efficacy endpoint of objective response rate, evaluating responses achieved by Week 25 and confirmed by Week 33 (Pegram et al, Br J Cancer 2019). Furthermore, using data collected up to 378 days after randomization, there were no notable differences in progression-free survival, overall survival (OS), safety, or immunogenicity. Here, we report additional cumulative safety and OS data collected up to 5 years after the first patient was screened. Methods: Eligible patients were randomized 1:1 to receive intravenous Trazimera or Herceptin-EU, each plus paclitaxel. Randomization was stratified by prior trastuzumab exposure and estrogen receptor status. Trazimera or Herceptin-EU treatment could continue until objective disease progression per RECIST 1.1. In addition to evaluating safety and OS in the overall study population, we assessed safety in the subgroup of patients still ongoing in the study after Day 378 (including only adverse events starting after this time point). We also compared time to discontinuation from Trazimera or Herceptin-EU. Results: Of 707 patients randomized (Trazimera, n=352; Herceptin-EU, n=355), 83 (11.7%) were ongoing in the study as of the data cutoff on February 25, 2019 (Trazimera, n=41 [11.6%]; Herceptin-EU, n=42 [11.8%]). Overall, 637 (90.1%) patients discontinued trastuzumab treatment (Trazimera, n=319 [90.6%]; Herceptin-EU, n=318 [89.6%]). The most frequent reason for discontinuing trastuzumab was objective progression (Trazimera, n=245 [69.6%]; Herceptin-EU, n=245 [69.0%]). Estimated median time to discontinuation from trastuzumab was 12.25 months for Trazimera and 12.06 months for Herceptin-EU (stratified hazard ratio [HR] 1.014; 95% confidence interval [CI] 0.867-1.186; log-rank P=0.569). In total, 58 (16.5%) patients in the Trazimera group and 67 (18.9%) patients in the Herceptin-EU group died. There was no statistically significant difference in OS (stratified HR 0.888; 95% CI 0.624-1.264; log-rank P=0.254). Estimated 2-year survival rates were 82.26% for Trazimera and 77.50% for Herceptin-EU; corresponding estimated 3-year rates were 77.17% and 75.33%. Among patients who received treatment (Trazimera, n=349; Herceptin-EU, n=353), there were no notable differences in incidences of treatment-emergent adverse events (TEAEs; 98.3% vs. 96.6%), grade 3 or higher TEAEs (40.7% vs. 42.5%), or serious TEAEs (19.2% vs. 19.3%). Rates of cardiac failure (1.4% vs. 2.8%), infusion-related reaction (IRR; 9.7% vs. 9.1%), and decreased ejection fraction (13.2% vs. 13.0%) were similar. Comparable proportions of patients had ≥1 occasion of an absolute decrease in left ventricular ejection fraction of ≥16% from baseline (6.3% vs. 5.4%) or ≥10% from baseline and below the lower limit of normal (4.0% vs. 5.1%). In the subgroup ongoing after Day 378 (Trazimera, n=265; Herceptin-EU, n=264), rates of cardiac failure (0.0% vs. 1.1%), IRR (0.0% vs. 0.8%), and decreased ejection fraction (3.4% vs. 4.2%) remained balanced. Conclusion: Long-term safety and OS data were consistent with previous results from this ongoing comparative study of Trazimera and Herceptin-EU, demonstrating no clinically meaningful differences between treatment groups. These results represent the longest known follow-up data reported for a trastuzumab biosimilar study in patients with HER2-positive MBC. Funding: This study was sponsored by Pfizer.
Citation Format: Rubi K Li, Oleg Lipatov, Hryhoriy Adamchuk, Vladimir Vladimirov, Eduardo Yanez, Patricia Banchero, Amy Freyman, Fiona Hilton, Alexandra Thiele, Alicia Vana. Trazimera (a trastuzumab biosimilar) in HER2-positive metastatic breast cancer: Long-term safety and overall survival data [abstract]. In: Proceedings of the 2019 San Antonio Breast Cancer Symposium; 2019 Dec 10-14; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2020;80(4 Suppl):Abstract nr P1-18-08.