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Trastuzumab Biosimilar With PIK3CA Inhibitor Shows Efficacy in Advanced Breast Cancer


Two studies of trastuzumab biosimilars have improved understanding of these medicines as monotherapy and in combination with other agents in metastatic breast cancer.

Studies of trastuzumab biosimilars in human epidermal growth factor receptor 2 (HER2)-positive metastatic breast cancer (mBC) have yielded significant findings, according to presentations at the 2020 San Antonio Breast Cancer Symposium.

PIK3CA Pathway Inhibitor Combination

Investigators achieved a 45.5% response rate in patients with HER2-positive mBC and PIK3CA aberrations who were treated with the trastuzumab biosimilar Herzuma and an experimental PIK3CA pathway inhibitor (gedatolisib, PF-05212384) in a phase 2 pilot trial.1

PI3KCA pathway aberrations tend to promote tumor cell growth and survival despite treatment with monoclonal antibodies, chemotherapy, and radiotherapy. The study authors hypothesized the combination of trastuzuamb and gedatolisib would improve outcomes for select patients with disease progression who had exhausted approved treatment options for mBC.

They enrolled 15 patients with HER2-positive mBC with a known PIK3CA pathologic mutation or amplification (1047R, H1047L, E542Q, E542K, E453K, N345K) and who had failed on multiple prior lines of therapy. Patients received a trastuzumab biosimilar 8 mg/kg intravenously for the first cycle and then 6 mg/kg every 3 weeks plus gedatolisib 180 mg on days 1, 8, and 15 every 21 days.

As of the data cutoff on August 4, 2020, 11 patients were eligible for response assessment. Five achieved partial response as their best response; 3, stable disease; and 3, progressive disease. All patients with partial response remain on the investigational treatment, with the longest term being 7.8 months. Among the patients with stable disease, 1 discontinued due to disease progression and 2 continue to receive therapy. The investigators said the disease control rate was 72.7% with no treatment-related fatal adverse events.

Ogivri PK Equivalence Study

A multicenter, global, phase 3 study of the trastuzumab biosimilar MYL-1401O (Ogivri) in patients with HER2-positive mBC has demonstrated pharmacokinetic (PK) equivalence between the biosimilar and the reference product (Herceptin).2

Ogivri, a Mylan/Biocon product, was approved by the FDA in December 2017 and marketed in the United States December 2019.

Investigators randomized 485 patients 1:1 to receive the biosimilar or reference product, with the aim of assessing biosimilarity on the basis of efficacy, safety, population PK, and immunogenicity. They said 482 patients were included in the population PK analysis.

The measures for drug exposure at or near steady-state dosing were comparable for Ogivri and the reference drug, demonstrating PK biosimilarity, the investigators said. Steady state is the time the concentration of the drug in the body stays consistent during administration, with the amount of drug entering the patient’s system being equivalent to the rate of elimination.

Other measures of PKs also supported equivalence, they said. “Population PK profiles of [Ogivri] vs Herceptin were similar in patients with HER2-positive mBC. Model-based exposure measures were similar between treatments.”

They added that extracellular domain fragments of the HER2 receptor “were a strong determinant of trastuzumab clearance [elimination], and clearance was similar between [biosimilar and reference drug] treatments.” They observed that trough concentrations—drug concentrations immediately before the next dose—were similar between treatments at the end of cycle 1 and at cycle 6.


1. Kim JW, Ahn HK, Choi JG, et al. Phase II pilot study of trastuzumab biosimilar (Herzuma) plus gedatolisib in patients with HER-2 positive metastatic breast cancer who progressed after 2 or more HER-2 directed chemotherapy [KM-10A/KCSG18-13 interim analysis]. Presented at: SABCS; December 8-11, 2020. Abstract PS11-39. www.sabcs.org/portals/sabcs2016/2020%20SABCS/Final%20PDF%20Docs%20111620_All%20PDF%20File%20No%20Embargoed%20Abstracts.pdf

2. Owen J, Rackley R, Liu M, et al. Population pharmacokinetics (pop PK) of MYL‑1401O (a trastuzumab biosimilar) and reference trastuzumab (Herceptin) in patients with HER2‑positive metastatic breast cancer (mBC). Presented at: SABCS; December 8-11, 2020. Abstract PS18-23. www.sabcs.org/portals/sabcs2016/2020%20SABCS/Final%20PDF%20Docs%20111620_All%20PDF%20File%20No%20Embargoed%20Abstracts.pdf

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