HER2 Expression Determines Benefit of Sacituzumab Govitecan in HR+ Breast Cancer

For those pre-treated with CDK4/6 inhibitors or prior chemotherapy for advanced hormone receptor (HR)-positive, HER2-negative breast cancer, sacituzumab govitecan (Trodelvy) is a “nice choice” for patients, according to Sara M. Tolaney, MD, MPH.

CancerNetwork^® spoke with Tolaney, chief of the Division of Breast Oncology and associate director of the Susan F. Smith Center for Women’s Cancer at Dana-Farber Cancer Institute, and associate professor of medicine at Harvard Medical School, in Boston, ahead of the FDA’s approval of sacituzumab govitecan in HR-positive, HER2-negative breast cancer.¹

Approval of sacituzumab in this patient population was supported by data from the phase 3 TROPiCS-02 trial (NCT03901339), in which the agent produced a 34% reduction in the risk of progression or death compared with standard chemotherapy.²

Tolaney also spoke about the specific benefits of sacituzumab compared with similar agents including trastuzumab deruxtecan (T-DXd; Enhertu), distinguishing their uses based on HER2 expression. “…T-DXd really is just for those patients who are HER-2 low at this time,” she explained. “So, for those patients who are HER2-zero, using sacituzumab earlier is really nice.”

Tolaney also briefly discussed the next steps in researching the use of sacituzumab in earlier clinical settings.

Transcript:

Right now, the data that we have for sacituzumab really did focus on those patients who had 2 to 4 lines of prior chemotherapy for metastatic disease. TROPiCS-02 did allow patients to have had 1 line if they had had early relapse after their adjuvant therapy. The right population [for sacituzumab] is someone who's had prior chemotherapy in the metastatic setting and prior CDK4/6 inhibition; then this agent becomes a very nice choice.

One of the conundrums that's often coming up in the clinic currently is we do have trastuzumab deruxtecan [T-DXd] as an alternative option to chemotherapy in hormone receptor-positive disease, and now we will have sacituzumab. And so, how does one think about sequencing them? Again, the T-DXd really is just for those patients who are HER2-low at this time. So, for those patients who are HER2-zero, using sacituzumab earlier is really nice. [It is] even [useful] in HER2-low [disease] given the setting where this agent was studied; it certainly can be used post–T-DXd, as well.

But it's really important that we get more data for using sacituzumab [in earlier lines of treatment]. There are actually ongoing trials addressing this. There's a first-line study in the metastatic setting looking at sacituzumab compared to standard therapy. And our group actually also has a study combining sacituzumab with immunotherapy in hormone receptor-positive disease, as well.

References

1. U.S FDA approves Trodelvy in pre-treated HR+/HER2- metastatic breast cancer. News release. Gilead. February 3, 2023. Accessed February 3, 2023. https://bwnews.pr/3Y0bftX
2. U.S. FDA accepts for priority review the supplemental biologics license application for Gilead’s Trodelvy® for pre-treated HR+/HER2- metastatic breast cancer. News release. Gilead Sciences. October 11, 2022. Accessed February 2, 2023. Bit.ly/3YifctN