Dr Waks on Later-Line Treatment Options in HER2+ Breast Cancer

Adrienne G. Waks, MD, physician, associate director of Clinical Research, Dana-Farber Cancer Institute, instructor in medicine, Harvard Medical School, discusses treatment alternatives in the third line and beyond for patients with metastatic HER2-positive breast cancer. 

A potential treatment option for patients in the third line is the novel monoclonal anti-HER2 antibody margetuximab-cmkb (Margenza), Waks begins. Due to its immune-activating properties, margetuximab could serve as a potential substitute for trastuzumab (Herceptin) in chemoimmunotherapy regimens, Waks says. The agent was approved by the FDA in 2020 alongside chemotherapy for adult patients with metastatic HER2-positive breast cancer who received 2 or more prior HER2-targeted therapies, including 1 in the metastatic setting. The approval was supported by data from the phase 3 SOPHIA trial (NCT02492711).

Another alternative treatment option is the regimen from the phase 2 monarchHER trial (NCT02675231) of fulvestrant (Faslodex), abemaciclib (Verzenio), and trastuzumab, Waks continues. MonarcHER evaluated this triplet in patients with hormone receptor (HR)–positive, HER2-positive breast cancer previously treated with 2 or more prior lines of therapy. Although this was not a phase 3 trial, all agents are approved by the FDA, Waks notes, adding that the approach was well tolerated and does not include a chemotherapy agent. This makes it an attractive option for some patients who have been treated with chemotherapy alone or in addition to targeted therapy for several years, she explains.

Although it remains the oldest available antibody-drug conjugate (ADC) utilized in this space, strategies involving ado-trastuzumab emtansine (Kadcyla; T-DM1) remain a viable option for patients with HER2-positive disease, Waks notes. The phase 3 HER2CLIMB-02 trial (NCT03975647) is currently investigating whether adding tucatinib to T-DM1 will improve efficacy outcomes vs single-agent T-DM1 in patients with HER2-positive disease previously treated with trastuzumab or a taxane in any disease setting, she concludes.

Disclosures: Dr. Waks reports serving as a consultant or in an advisory role for AstraZeneca; she received research funding from Genentech, MacroGenics and Merck.