Chinese Trastuzumab Biosimilar Demonstrates Equivalency in HER2+ Breast Cancer

The Chinese-manufactured trastuzumab biosimilar HLX02 demonstrated similar objective response rates to the reference product at 24 weeks in patients with treatment-naïve or recurrent metastatic HER2-positive breast cancer.

Binghe Xu, MD, PhD

The Chinese-manufactured trastuzumab (Herceptin) biosimilar HLX02 demonstrated similar objective response rates (ORRs) to the reference product at 24 weeks in patients with treatment-naïve or recurrent metastatic HER2-positive breast cancer, according to results of a phase III trial (NCT03084237) that were presented at the 2019 ESMO Asia Congress.1,2

Specifically, the ORR at 24 weeks was 71.0% with HLX02 versus 71.4% with European Union (EU)—sourced trastuzumab (P = .952). The risk difference in ORRs between the 2 groups was —0.4% (95% CI –7.4-6.6), which was within the predefined margin of ±13.5%.

Regarding safety, the rates of adverse events (AEs) and treatment-emergent AEs (TEAEs) were similar between the biosimilar and reference trastuzumab; there were also no differences in safety profiles or immunogenicity.

The interim results have been submitted to the China National Medical Products Administration and European Medicines Agency (EMA) to support approval of HLX02 in China and Europe, respectively.

“Trastuzumab is not widely accessible around the world due to its high cost. The entry of more affordable versions of trastuzumab such as HLX02 could open up treatment access,” study first author Binghe Xu, MD, PhD, of the Department of Medical Oncology, Cancer Hospital Chinese Academy of Medical Sciences in Beijing, China, stated in a press release. “Overall response rate at week 24 was similar for HLX02 and reference trastuzumab with no statistical difference observed between the two treatment groups.”

In the double-blind, parallel-controlled, phase III trial, investigators randomized 649 female patients with HER2-positive breast cancer that was previously untreated or recurrent to receive HLX02 (n = 324) or reference EU-sourced trastuzumab (n = 325), both at an 8 mg/kg dose with docetaxel on day 1. This was followed by a 6 mg/kg dose in three-week cycles for up to 12 months.

The primary endpoint was ORR at week 24; secondary endpoints included clinical benefit rate (CBR), disease control rate (DCR), duration of response (DOR), progression-free survival (PFS), overall survival (OS), safety profiles, and ORR at weeks 6, 12, and 18.

Prior results demonstrated clinical pharmacokinetic equivalence between the 2 drugs.3

The updated results also showed that the DCR was 83.0% and 84.3% with the biosimilar and reference trastuzumab, respectively (P = .646). Additionally, the median PFS was 11.7 months with HLX02 and 9.69 months with trastuzumab (P = .079). ORRs at weeks 6, 12, and 18; CBR, DOR, and OS at week 24 were also found to be similar for HLX02 and EU-trastuzumab.

Similar range values of CBR were reported for both groups in the overall, Asian versus non-Asian, and Chinese versus non-Chinese populations: (HLX02, 78.6%-86.8%; EU-trastuzumab: 79.3%-82.4%). Also in these populations, similar range values were also reported for DCR (HLX02, 80.6%-95.4%; EU-trastuzumab, 86.9%-89.2%).

A total 98.8% of patients in each arm reported ≥1 AE or TEAE.

“HLX02 is equally safe and effective as the reference trastuzumab and has been rigorously evaluated by regulatory authorities such as the European Medicines Agency, based on sound scientific principles,” concluded Xu in the press release. “HLX02 has a clear potential to drive down spending on HER2-positive cancer treatment. Xu did add in the press release that the price of the biosimilar has not yet been agreed.

Rosa Giuliani, MD, a consultant medical oncologist, Clatterbridge Cancer Centre, Liverpool, United Kingdom, commented on the findings in the press release.

“The development of biosimilars is important both for patients, by improving access to cancer drugs, and for health systems, allowing cost savings that can be reinvested in patient care and support the sustainability of healthcare systems,” Giuliani said. “Biosimilars are safe and effective drugs which can finally allow those patients to receive an appropriate standard of care.”


  1. Xu B, Zhang Q, Sun T, et al. First China-manufactured trastuzumab biosimilar HLX02 global phase III trial met primary endpoint in breast cancer. Presented at: ESMO Asia Congress 2019; November 22-24, 2019; Singapore. Abstract LBA6.
  2. First China-manufactured Trastuzumab Biosimilar HLX02 Global Phase III Trial Met Primary Endpoint in Breast Cancer. European Society for Medical Oncology. Published November 22, 2019. Accessed November 22, 2019.
  3. Zhang Q, Xu B, Zhang Q, et al. Global clinical trials validating bioequivalence with China-manufactured trastuzumab biosimilar, HLX02, and Herceptin. Ann Oncol. 2018;29(suppl_9):ix13-ix20. doi: 10.1093/annonc/mdy428.