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Biosimilar-Gedatolisib Combo Elicits Response in Resistant mBC


In metastatic breast cancer (mBC) resistant to multiple lines, Herzuma (a trastuzumab biosimilar) plus gedatolisib, an mTOR/PI3K signaling pathway inhibitor, demonstrated value.

In midterm results for a phase 2 study presented at the the 2021 San Antonio Breast Cancer Symposium, a trastuzumab biosimilar (Herzuma) in conjunction with gedatolisib, a cell-signaling inhibitor, demonstrated an overall response rate of 58.8% with manageable toxicity in patients with human epidermal growth factor receptor 2 (HER2)–positive metastatic breast cancer (mBC) with a PIK3CA aberration.

The disease control rate achieved with this combination was 82.4%, investigators said. Median progression-free survival was 5.9 months.

Trastuzumab is a monoclonal antibody that targets HER2, which is overexpressed in cancers and contributes to excessive cell growth. Trastuzumab binds to the HER2/neu receptor and reduces HER2 expression and also reduces growth of blood vessels that support tumor growth.

Gedatolisib targets the mTOR/PIK3 signaling pathway, which plays a role in tumor growth and proliferation. mTOR is a protein whose signaling regulates cell metabolism, growth, proliferation and survival. And PI3K is a group of enzymes that also regulate cell growth and are implicated in the development of cancer.

In the trial, investigators sought to elucidate the value of trastuzumab in combination with gedatolisib in patients whose cancers had progressed after multiple lines of therapy.

Resistance to anti-HER2 agents with antibody-drug conjugates (ADCs) is common, especially along the mTOR/PI3K signaling pathway. ADCs combine an antigen-specific antibody with a cytotoxic payload. At least 2 anti-HER2 ADCS have been approved for HER2-positive breast cancer. One is ado-trastuzumab emtansine, which was initially approved in 2013. Another was trastuzumab deruxtecan, approved in 2020.

In this study, patients were enrolled who had HER2-positive mBC with a known PIK3CA pathologic mutation or amplification whose disease had progressed following ≥ 2 HER2-directed therapies. Patients were treated with the trastuzumab biosimilar plus gedatolisib until progression or intolerable toxicity.

Median age of patients (N = 17) was 54.5 years and premenopausal (11.8%) and menopausal (88.2%) patients were enrolled.

Following therapy, investigators said 3 patients had progressive disease, 4 had stable disease, and 10 showed a partial response. The trial will continue with enrollment up to a target 62 patients.


Kim JW, Ahn HK, Choi JG, et al. Phase II 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 (KCSG BR 18-13) interim analysis. Presented at: 2021 SABCS; December 7-10, 2021. Poster PS16-03.

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