The trastuzumab biosimilar HLX02—manufactured in China—achieved a similar overall response rate to reference trastuzumab in women with HER2-positive recurrent or previously untreated metastatic breast cancer, according to a large, randomized phase III study reported by Xu et al at the European Society for Medical Oncology (ESMO) Asia Congress 2019 (LBA6).

HXLO2 was developed in consultation with China National Medical Products Administration (CNMPA) and European Medicines Agency (EMA) for global development.

“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,” said first study author Binghe Xu, MD, PhD, of the Department of Medical Oncology, Cancer Hospital Chinese Academy of Medical Sciences.

The anti-HER2 antibody trastuzumab given in combination with chemotherapy has significantly improved overall survival in patients with HER2-positive breast cancer, and become the standard of care over the past decade. However, the cost can limit patient access to this treatment in regions with limited financial resources for health care, according to a study by Lammers et al published in Pharmaceuticals.

Study Findings

The phase III study randomized 649 women with HER2-positive recurrent or previously untreated metastatic breast cancer to HLX02 or European Union–sourced trastuzumab (EU-TZB) (dose of 8 mg/kg for both drugs) with docetaxel on day 1. Cycle 1 was followed by a dose of 6 mg/kg in three-weekly cycles for up to 12 months. The women were recruited from 89 centers in China, the Philippines, Poland, and Ukraine.

Result showed similar overall response rate at 24 weeks with HLX02 (71.0%) as with EU-TZB (71.4%, P = .952). The risk difference in overall response rates between the two groups was -0.4% (95% confidence interval [CI] = 7.4–6.6), which was within the predefined margin (+13.5%).

All secondary endpoints—including overall response rates at weeks 6, 12, and 18; clinical benefit rate; disease control rate; duration of response; progression-free survival; and overall survival at week 24—were similar for HLX02 and EU-TZB. The disease control rate was 83.0% in the HLX02 group and 84.3% in the reference trastuzumab group (P = .646). The median progression-free survival with HLX02 was 11.7 months compared to 9.69 months with trastuzumab (P = .079).

In each treatment group, 98.8% of the patients reported at least one adverse event or treatment-emergent adverse event, and a similar number of adverse events were reported in the two treatment groups. There were no differences in safety profiles or immunogenicity between HLX02 and reference trastuzumab.

“HLX02 is equally safe and effective as the reference trastuzumab, and has been rigorously evaluated by regulatory authorities such as the EMA based on sound scientific principles,” said Dr. Xu. He added, “HLX02 has a clear potential to drive down spending on HER2-positive [breast] cancer treatment,” although he said the price has not yet been agreed.

Commentary

Rebecca Dent, MD

Rebecca Dent, MD, Head of Medical Oncology at the National Cancer Center Singapore, added, “The development of biosimilars means that more women will have access to potentially lifesaving HER2-targeted therapies because of the cost savings they provide. Development of biosimilars introduces competition and potentially lowers the price of drugs. As more biosimilar therapies are being developed, there is also a need for vertical integration of the biomarkers that identify patients who will benefit.”

For trastuzumab biosimilars, this means ensuring access to HER2 status testing.

Reviewing the quality of the study design, Dr. Dent considered it important that the clinical program with HLX02 was developed in consultation with the EMA and the CNMPA. The interim results of the study have been submitted to the CNMPA and EMA to support approval of HLX02 in China and Europe.

Disclosure: For full disclosures of the study authors, visit academic.oup.com.