Biosimilar Trastuzumab Effective in Triplet Regimen for Gastric Cancer

July 10, 2020

A phase 1b/2 trial evaluating a trastuzumab biosimilar as part of a first-line triplet regimen demonstrated significant tumor shrinkage in HER2-positive advanced gastric cancer.

Biosimilar trastuzumab (Herzuma) in combination with pembrolizumab and chemotherapy was highly effective in reducing tumor size in patients with HER2-positive advanced gastric cancer, according to results of a phase 1b/2 clinical trial.

The PANTHERA trial was designed to evaluate the potential of the combination therapy in light of a growing body of evidence on the positive effects of monoclonal antibodies such as trastuzumab in treating solid tumors.The findings have implications for reducing the costs of care, the authors said.

“With the costs of oncology treatments being so burdensome, the availability of biosimilar trastuzumab could reduce the overall cost by combination treatment with innovative new drugs and chemotherapy,” said Sun Young Rha, MD, PhD, chief of medical oncology at Yonsei University College of Medicine and the lead investigator of the trial, during her presentation on the results at this year's virtual 2020 American Society of Clinical Oncology Annual Meeting.

The study was recently highlighted by the Journal of Clinical Pathways.

Details on the PANTHERA trial

Investigators in the Republic of Korea enrolled 43 patients and treated them with pembrolizumab (200 mg, day 1), biosimilar trastuzumab (6 mg/kg, day 1), capecitabine (1000 mg/m2 twice daily, days 1-14), and cisplatin (80 mg/m2, day 1 every 3 weeks).

The treatment duration ranged from 1.4 to 24 months, with a median follow up of 16.1 months. The trial enrolled 43 patients and 11 remained on the regimen.

Investigators found significant tumor shrinkage in 95.3% of patients, and the overall response rate was 76.7%. They said 16.3% of patients experienced a complete response and 60.5%, a partial response. Additionally, the median progression-free survival was 8.6 months (95% CI, 7.2-16.4), and the median overall survival (OS) was 19.3 months (95% CI, 16.5-NA). The investigators also found that positive status for the PD-L1 protein for patients at diagnosis did not significantly affect OS rates.

Treatment-related adverse events (AEs) ≥ grade 3 occurred in 32 (74.4%) patients, including 17 (39.5%) cases of grade 3 or grade 4 neutropenia. Immune-related AEs occurred in 4 (10%) patients. The most common hematologic AEs were decreased neutrophil count and anemia, which occurred in 46.5% and 32.6% of patients, respectively.

More on Herzuma

Herzuma, developed by Teva Pharmaceuticals USA and Celltrion Healthcare, is indicated for treatment in patients with HER2-positive metastatic breast cancer, early breast cancer, and metastatic gastric cancer.

It was approved for use in the United States in December 2018 and launched in March 2020, making it the fourth trastuzumab biosimilar to be approved in the United States.

The drug was approved in the European Union in November of 2017 and launched there in May 2018. Herzuma also is approved in the Republic of Korea, Japan, and Brazil.

Reference

Rha SY, Lee CK, Kim HS, et al. Targeting HER2 in combination with anti-PD-1 and chemotherapy confers a significant tumor shrinkage of gastric cancer: A multi-institutional phase Ib/II trial of first-line triplet regimen (pembrolizumab, trastuzumab, chemotherapy) for HER2-positive advanced gastric cancer (AGC). J Clin Oncol. 2020;38(suppl 15; abstract 3081). doi:10.1200/JCO.2020.38.15_suppl.3081


x