Trastuzumab Biosimilar Passes Phase III Test for HER2+ Breast Cancer

Sean E. Harper, MD

The biosimilar ABP 980 demonstrated similar pathologic complete response (pCR) rates as the reference product trastuzumab (Herceptin) in a phase III study for patients with HER2-positive early breast cancer, according to findings announced by the codevelopers of the biosimilar, Amgen and Allergan.

The phase III study included a neoadjuvant stage, in which ABP 980 and trastuzumab were administered with chemotherapy followed by surgery. After this portion of the study, both agents were given as monotherapy in the adjuvant setting. ABP 980 demonstrated a pCR rate within a margin of +/-13% compared with trastuzumab, which was the criterion for equivalence. The adverse event (AE) profile was comparable between the two agents, with slightly more AEs seen with ABP 980 in the neoadjuvant portion of the study compared with trastuzumab.

"We believe this study confirms no clinically meaningful differences between ABP 980 and trastuzumab, and we look forward to continued discussions with regulatory authorities," Sean E. Harper, MD, executive vice president of Research and Development at Amgen, said in a statement. "Biosimilars are approved based on the analytical, nonclinical and clinical data, and we believe that the totality of the evidence we've generated supports ABP 980 as highly similar to the reference product."

The phase III study randomized 725 patients in a 1:1 ratio to receive ABP 980 (n = 364) or trastuzumab (n = 361). The pCR rates were assessed at the time of surgery for the last patient enrolled in the study. The final safety analysis is not yet complete and will be conducted once the last enrolled patient finishes treatment in the adjuvant setting.

In the neoadjuvant portion of the study, patients received epirubicin and cyclophosphamide followed by the biologic and paclitaxel. Breast and sentinel node or axillary lymph node resection was completed within 3 to 7 weeks after the last dose of therapy. Locoregional treatment may have included lumpectomy or mastectomy. In the adjuvant setting, patients received the same biologic every 3 weeks until a full year of therapy had been given.

On the lower end of the pCR spectrum, ABP 980 statistically showed that it was not inferior to trastuzumab; however, equivalence could not be shown on the high end of the pCR rate, as some patients had better pCR rates with ABP 980 versus trastuzumab. The upper end of the confidence interval was 13.4% with ABP 980, according to the companies.

In combination with chemotherapy in the neoadjuvant portion of the study, patients in the ABP 980 arm had more serious AEs compared with the trastuzumab group; however, investigators did not believe these were related to the biosimilar. In the adjuvant space, the serious AEs were similar in each group.

"These results provide significant clinical evidence that ABP 980 could be an important biosimilar treatment option for patients with HER2-positive early breast cancer," David Nicholson, chief research and development officer, Allergan, said in a statement. "Allergan is committed to the continued development of ABP 980 and other biosimilars that provide safe, high-quality and effective therapies in key disease areas."

Biosimilars are meant to foster competition and lower prices, and are defined as biological products that are "similar" or “interchangeable” with an FDA-licensed biological product, according to the US biosimilar pathway that was created under the Affordable Care Act.

An agent is considered a biosimilar if it is proven to be highly similar to an already approved biologic therapy, based upon analytical, animal, and clinical studies assessing immunogenicity, pharmacokinetics (PK), or pharmacodynamics (PD). The treating physicians must prescribe these agents; however, biosimilars are considered interchangeable if they demonstrate similar clinical outcomes compared with the reference product in a larger clinical trial, such as a phase III study. Interchangeable agents can be substituted by a pharmacist without the intervention of the prescribing healthcare provider, according to the FDA.

The first FDA-approved biosimilar in the United States was filgrastim-sndz (Zarxio). This agent gained FDA approval in March 2015 and finally reached the market in September 2015, following a series of lawsuits and court decisions. The biosimilar G-CSF analog, which is manufactured by Sandoz, was approved for all five indications as a non-interchangeable biosimilar for its counterpart Neupogen (filgrastim), which is made by Amgen. This biosimilar was launched at a 16.2% discount compared with the reference product.