Assessing the Future With “Promising” Antibody Drug Conjugates in Breast Cancer

CancerNetwork^® spoke with Paolo Tarantino, MD, about potential treatment advances in the breast cancer space, particularly those related to using antibody drug conjugates (ADCs).

Tarantino, a clinical research fellow at Dana-Farber Cancer Institute and Harvard Medical School, discussed data supporting topoisomerase 1 (TOP1) inhibitor ADCS in different treatment settings such as triple-negative breast cancer; investigators presented some of these findings at the 2024 American Society of Clinical Oncology (ASCO) Annual Meeting. Beyond TOP1 ADCS, he highlighted enfortumab vedotin-ejfv (Padcev) as an example of therapy with an alternative target.

Transcript:

Beyond T-DXd, datopotamab deruxtecan is similar to T-DXd but [has] a different antibody that targets TROP2 and has slightly less chemotherapy attached to the agent. This drug has positive phase 3 data in hormone receptor–positive disease, and we expect it may be approved for this disease based on the TROPION-Breast01 trial [NCT05104866].¹

Sacituzumab govitecan-hziy [Trodelvy] is also a TROP2-directed ADC with a topoisomerase 1 inhibitor approved both for triple negative breast cancer² and hormone receptor–positive disease.³ We are now running the first trial in HER2-positive breast cancer with sacituzumab govitecan called SATEEN [NCT06100874], and we also hope to find a response and activity in that setting.

Beyond all this, there was also an interesting agent, SKB264, also called sacituzumab tirumotecan, with positive phase 3 trial [NCT05347134] data presented at ASCO in pretreated triple-negative breast cancer.⁴

All of these ADCs I mentioned are all topoisomerase 1 ADCs. They all deliver different flavors of the same chemotherapy. I do hope that we’re going to move beyond that, as well. We are learning that TOP1 ADCs are extremely effective, and they can change the trajectory of disease in certain patients with metastatic breast cancer. We need to also expand upon these [treatments]. There were some data on enfortumab vedotin-ejfv [Padcev] presented by Antonio Giordano, MD, PhD, at ASCO showing about 20% rate of response.⁵ This was the biomarker selected, but maybe we can increase [the response] if we select certain biomarkers. There is a suggestion that nectin-4 amplifications may help with that.

I hope that I gave sense of how much is going on in the field, how many promising ADCs are here, and how many promising ADCs have positive data in phase 3 trials, or even just high rates of response in phase 2 trials. In the next few years, we’ll see many of those having positive phase 3 trials being approved and providing more options to treat our patients with metastatic breast cancer.

References

1. Pernas S, Im S, Hattori M, et al. Datopotamab deruxtecan (Dato-DXd) vs chemotherapy (CT) in previously treated inoperable or metastatic hormone receptor-positive, HER2-negative (HR+/HER2–) breast cancer (BC): patient-reported outcomes (PROs) from the TROPION-Breast01 study. J Clin Oncol. 2024;42(suppl 16):1006. doi:10.1200/JCO.2024.42.16_suppl.1006
2. FDA grants regular approval to sacituzumab govitecan for triple-negative breast cancer. News release. FDA. April 7, 2021. Accessed June 20, 2024. https://tinyurl.com/6p89bpuv
3. U.S FDA approves Trodelvy in pre-treated HR+/HER2- metastatic breast cancer. News release. Gilead. February 3, 2023. Accessed June 20, 2024. https://bwnews.pr/3Y0bftX
4. Xu B, Yin Y, Fan Y, et al. Sacituzumab tirumotecan (SKB264/MK-2870) in patients (pts) with previously treated locally recurrent or metastatic triple-negative breast cancer (TNBC): results from the phase III OptiTROP-Breast01 study. J Clin Oncol. 2024;42(suppl 16):104. doi:10.1200/JCO.2024.42.16_suppl.104
5. Giordano A, Awan AA, Bruce JY, et al. Enfortumab vedotin (EV) in triple-negative breast cancer (TNBC) and HR+/HER2- breast cancer (BC) cohorts of EV-202. J Clin Oncol. 2024;42(suppl 16):1005. doi:10.1200/JCO.2024.42.16_suppl.1005