Analyzing Emerging Therapies Across Breast Cancer Subtypes

Erika Hamilton, MD, gave an overview to CancerNetwork® of her presentation from the 2025 International Congress on the Future of Breast Cancer® East hosted by Physicians' Education Resource®, LLC, focusing on 3 different types of breast cancer.¹ Through her presentation, she also focused on various trials and emerging therapies.

Hamilton, director of breast cancer and gynecologic cancer research at Sarah Cannon Research Institute, highlighted results from the phase 3 VERITAC-2 trial (NCT05654623) presented at the 2025 American Society of Clinical Oncology (ASCO) Annual Meeting, which assessed vepdegestrant vs fulvestrant for patients with estrogen receptor (ER)–positive, HER2-negative ESR1-mutant advanced or metastatic breast cancer.² The median progression-free survival between either arm was 5.0 months (95% CI, 3.7-7.4) and 2.1 months (95% CI, 1.9-3.5), respectively (stratified HR, 0.57; 95% CI, 0.42-0.77; 2-sided P < .001).

Regarding antibody-drug conjugates (ADCs), Hamilton also touched upon the phase 3 DESTINY-Breast09 (NCT04784715) of fam-trastuzumab deruxtecan-nxki (Enhertu) in various combinations for patients with HER2-positive metastatic breast cancer.³

Transcript:

I divided this talk into the 3 different types of breast cancer: ER-positive disease, triple negative, and HER2 positive. In the ER-positive realm, we saw new data from an oral PROTAC [proteolysis-targeting chimeric] [degrader] at ASCO 2025 this year. Vepdegestrant beat fulvestrant in patients with ESR1 mutations.

We also touched on the antibody-drug conjugates for patients who are refractory with HER2-positive disease. We’ve recently seen data from DESTINY-Breast09, which was at ASCO, moving trastuzumab deruxtecan up into the first line. We anticipate a label expansion coming for that. One of the newer drugs I’m highlighting is zanidatamab-hrii (Ziihera), which is a biparatopic HER2 antibody, and this is in a large registrational phase 3 trial right now in breast cancer.

In terms of triple-negative [disease], antibody-drug conjugates are still the story. There are many new ones coming. One of the newer ones with recent data in May 2025 at ESMO Breast [European Society for Medical Oncology Breast Cancer Annual Congress] was Emi-Le or emiltatug ledadotin, which is a novel antibody-drug conjugate that has a new payload but also a new target. It’s a B7-H4 with a novel auristatin payload. What was particularly significant about this trial was that almost everyone had already seen sacituzumab govitecan and quite a few patients had already seen trastuzumab deruxtecan. It was exciting to see the activity of ADC after ADC.

References

1. Hamilton E. Exciting new therapies on the horizon. Presented at: 2025 International Congress on the Future of Breast Cancer East; July 11-12, 2025; New York, NY.
2. Hamilton E, De Laurentiis M, Jhaveri K, et al. Vepdegestrant, a PROTAC estrogen receptor (ER) degrader, vs fulvestrant in ER-positive/human epidermal growth factor receptor 2 (HER2)–negative advanced breast cancer: results of the global, randomized, phase 3 VERITAC-2 study. J Clin Oncol. 2025;43(suppl 17):LBA1000. doi:10.1200/JCO.2025.43.17_suppl.LBA1000
3. Tolaney S, Jiang Z, Zhang Q, et al. Trastuzumab deruxtecan (T-DXd) + pertuzumab (P) vs taxane + trastuzumab + pertuzumab (THP) for first-line (1L) treatment of patients (pts) with human epidermal growth factor receptor 2–positive (HER2+) advanced/metastatic breast cancer (a/mBC): interim results from DESTINY-Breast09. J Clin Oncol. 2025;43(suppl 17):LBA1008.