T-DXd May Be the Preferred ADC in HR+/HER2– Breast Cancer

For patients with triple-negative breast cancer (TNBC), extensive data support the use of sacituzumab govitecan-hziy (Trodelvy), with the option to receive fam-trastuzumab deruxtecan-nxki (T-DXd; Enhertu) later in treatment, according to Jade E. Jones, MD.

Jones, an assistant professor in the Department of Hematology and Medical Oncology at Emory University School of Medicine and medical oncologist at the Emory Winship Cancer Institute, spoke with CancerNetwork® about how sacituzumab govitecan compares with T-DXd for the treatment of patients with either hormone receptor (HR)–positive/HER2-negative breast cancer or TNBC.

She began by expressing excitement at having both antibody-drug conjugates (ADCs) as treatment options for these patient groups before highlighting findings from the phase 3 DESTINY-Breast04 trial (NCT03734029) showing that T-DXd was associated with significantly improved progression-free survival outcomes vs standard chemotherapy in both patient groups.¹ Jones further explained that findings from the phase 3 TROPiCS-02 trial (NCT03901339) support the use of sacituzumab govitecan in both the HR-positive and TNBC populations.²

Based on prior data, she expressed that T-DXd is generally used as the first ADC option in the HR-positive population and that sacituzumab govitecan is typically used as the first option in TNBC. Furthermore, she iterated that both patient populations have the option to receive a different ADC in later lines of treatment.

Transcript:

I’m excited that we have these new antibody-drug conjugates, and both [T-DXd and sacituzumab govitecan] have shown to be effective in [HR-positive, HER2-negative BC and TNBC] populations. But in terms of which one we’re giving these drugs to, we have to go to the data: who was on the trial and where they were treated. In the phase 3 DESTINY-Breast04 study, where T-DXd was given to [patients with] predominantly HR-positive [disease]—but a small population of [patients with TNBC], about 25%—we saw a significant improvement in progression-free survival over standard chemotherapy.

In terms of the TROPiCS-02 study, which showed sacituzumab govitecan could be effective in [patients with] HR-positive [disease], we [also] have data to support them in the triple-negative population. For sacituzumab govitecan in [patients with] HR-positive [disease], the progression-free survival wasn’t as long as [with T-DXd], but they were more heavily treated. For the most part, most people are using [T-DXd] first in our HR-positive [populations], but they can still get sacituzumab govitecan.

There is also a new ADC as well: a third ADC in that population. In the [TNBC population], there are much more data for sacituzumab [govitecan]. For the most part, people are using sacituzumab [govitecan] first for our [TNBC populations], but they can still get T-DXd later in their treatment.

References

1. Modi S, Jacot W, Iwata H, et al. Trastuzumab deruxtecan (T-DXd) versus treatment of physician’s choice (TPC) in patients with HER2-low unresectable and/or metastatic breast cancer: updated survival results of the randomized, phase 3 DESTINY-Breast04 study. Ann Oncol. 2023;34(suppl 2):334-335. doi:10.1016/j.annonc.2023.09.553
2. Rugo HS, Bardia A, Marmé F, et al. Overall survival with sacituzumab govitecan in hormone receptor-positive and human epidermal growth factor receptor 2-negative metastatic breast cancer (TROPiCS-02): a randomised, open-label, multicentre, phase 3 trial. Lancet. Published online August 23, 2023. doi:10.1016/S0140-6736(23)01245-X