FDA Approves Trastuzumab Biosimilar for HER2+ Breast Cancer


The FDA has granted an approval to CT-P6, a trastuzumab biosimilar, for the treatment of patients with HER2-overexpressing breast cancer

The FDA has granted an approval to CT-P6 (Herzuma; trastuzumab-pkrb), a trastuzumab (Herceptin) biosimilar, for the treatment of patients with HER2-overexpressing breast cancer, according to Celltrion and Teva Pharmaceutical Industries, the co-developers of the agent.1

CT-P6 is indicated for patients with adjuvant breast cancer of HER2 overexpressing node-positive or -negative breast cancer to be used as part of a treatment regimen comprised of doxorubicin, cyclophosphamide, and either paclitaxel or docetaxel, or as part of a regimen with docetaxel and carboplatin.

The biosimilar is also indicated as first-line treatment for patients with HER2-overexpressing metastatic breast cancer to be used in combination with paclitaxel, or as a single agent to treat HER2-positive breast cancer in patients who have received 1 or more chemotherapy regimens for metastatic disease.

“Biosimilars are of growing importance to the oncology community and the approval of Herzuma may provide more patients access to this important therapy,” said Woosung Kee, chief executive officer, Celltrion, in a press release. “This is our second oncology biosimilar approved in the United States in the past month, which reinforces the goal for all of our approved products—providing broader treatment options for patients and the providers who treat them.”

The approval is based on an extensive review of a comprehensive data package, which included foundational analytical similarity data, nonclinical data, clinical pharmacology, immunogenicity, clinical efficacy, and safety data, according to the news release.

Two-year follow-up findings from a double-blind, randomized phase III trial with CT-P6 were recently presented at the 2018 San Antonio Breast Cancer Symposium (SABCS). The data demonstrated that the biosimilar demonstrated long-term disease-free survival (DFS) and overall survival (OS) that were similar to trastuzumab in the treatment of patients with HER2-positive early breast cancer. These follow-up results confirmed the similar efficacy and safety that were observed at 1 year.2

During the SABCS presentation of the results, lead study author Francisco J. Esteva, MD, PhD, the director of Breast Medical Oncology at NYU Langone Health, said in the SABCS presentation that, “the findings are reassuring after 2 years, that [we’re] still getting similar results, which is important.”

The phase III trial compared the efficacy and safety of neoadjuvant and adjuvant trastuzumab and CT-P6 in 549 patients with HER2-positive stage I to IIIa operable breast cancer. Patients were randomized to either receive anthracycline- and taxane-based chemotherapy in combination with trastuzumab or chemotherapy in combination with CT-P6. After surgery, patients continued to receive trastuzumab or CT-P6 to complete 1 year of therapy.

A total of 528 patients were included in the follow-up period (259 in the CT-P6 arm and 269 in the reference arm). Median follow-up duration was 27 months at the data cutoff of November 30, 2017.

In the intention-to-treat (ITT) set, the proportion of 2-year DFS was 86% (95% CI, 80%-90%) in the CT-P6 arm and 90% (95% CI, 85%-93%) in the reference arm. In the per-protocol set, these percentages and confidence intervals were observed to be identical. Median DFS and OS had not been reached. In the ITT analysis, 2-year OS was 97% (95% CI, 93%-98%) in the CT-P6 arm, while it was 98% (95% CI, 96%-99%) in the reference arm. In the pre-protocol set, 2-year OS was 97% (95% CI, 94%-99%) and 98% (95% CI, 96%-99%), in the CT-P6 and reference arms, respectively.

Three-year OS data were also presented at the meeting, and were observed to have remained similar in the ITT analysis (92% [95% CI, 86%-96%] for the CT-P6 arm and 93% [95% CI, 87%-96%] for the reference arm) as well as the per-protocol set (94% [95% CI, 88%-97%] for the CT-P6 arm and 93% [95% CI, 86%-96%] for the reference arm).

Additionally, the mean ventricular ejection fraction (LVEF) was maintained at >55% during the 1 year on treatment as well as during the follow-up period. The median post-baseline worst LVEF value was 60 in both the CT-P6 arm (95% CI, 38-70) and the reference arm (95% CI, 30-76). In the CT-P6 arm, 29.5% of participants had a decrease in LVEF of ≥10 points, while this was observed in 25.2% of those in the reference arm; 3.3% and 2.5%, respectively, had an LVEF <50 and a decrease of ≥10 points.

Further, during the 1 year of treatment and follow-up, the rate of cardiac adverse events was 11.8% in the CT-P6 arm versus 13.7% in the reference arm. The rates of cardiac disorders deemed to be associated with the study drug was 8.1% and 8.6%, in the CT-P6 and reference arms, respectively, with most of the events categorized as grade 1 disorders. Rates of unrelated cardiac disorders were 5.2% and 6.8% in the CT-P6 and reference arms, respectively.

During the follow-up period, 1.1% of participants in the CT-P6 arm experienced a new cardiac event compared with 0.7% in the reference arm. The most common new event experienced by study participants were palpitations (3.7% in CT-P6 arm vs 2.9% in reference arm).

All trastuzumab product labels contain a boxed warning that the treatment may be linked with cardiomyopathy, infusion reactions, pulmonary toxicity, and embryo-fetal toxicity.

“We are excited about building Teva’s presence in biosimilars,” said Brendan O’Grady, the executive vice president and head of North America Commercial at Teva, in the press release. “The addition of Herzuma to our biosimilars portfolio will allow us to leverage our strengths from Oncology and Genetics.”


  1. Celltrion and Teva announce FDA approval of Herzuma (trastuzumab-pkrb), a biosimilar to Herceptin, for the treatment of HER2-overexpressing breast cancer for certain indications [news release]. Incheon, South Korea, and Jerusalem, Israel: Celltrion. Published December 14, 2018." . Accessed December 17, 2018.
  2. Esteva FJ, Lee S, Yu S, et al. 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). In: Proceedings from the 2018 San Antonio Breast Cancer Symposium; December 5-8; San Antonio, Tx. Abstract P6-17-03.
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