Dr Aditya Bardia Highlights TROPiCS-02 Biomarker Results for Sacituzumab Govitecan in Breast Cancer

Today at the 2024 annual meeting of the American Society of Clinical Oncology, Aditya Bardia, MD, MPH, FASCO, professor, Department of Medicine, Division of Hematology/Oncology; director, Translational Research Integration; and member, Signal Transduction and Therapeutics, UCLA Health, presented, “Genomic alterations in DNA damage response (DDR) genes in HR+/HER2- metastatic breast cancer (mBC) and impact on clinical efficacy with sacituzumab govitecan (SG): biomarker results from TROPICS-02 study.”¹

The phase 3 TROPiCS-02 trial (NCT03901339) studied the antibody-drug conjugate (ADC) sacituzumab govitecan vs physician’s choice of chemotharapy for HR+/HER2– breast cancer among individuals with a treatment history of prior taxane, endocrine therapy, CDK4/6 inhibitor, and 2 to 4 prior lines of chemotherapy.²

Transcript

Can you explain the TROPiCS-02 investigation and what were your primary goals?

TROPiCS-02 was a randomized phase 3 trial looking at a Trop-2–directed antibody-drug conjugate, sacituzumab govitecan, vs chemotherapy of physician's choice for patients with hormone receptor–positive, HER2-negative metastatic breast cancer. Overall, the trial showed improvement in progression free survival and overall survival, leading to approval of sacituzumab govitecan.

At ASCO 2024, we present biomarker analysis focusing more on the payload. Sacituzumab govitecan has SN-38 as the payload, which causes inhibition of Top-1 [topoisomerase 1]. The question was, if there is damage in the DNA repair pathway, or DDR, would that predict for more benefit sacituzumab govitecan based on the mechanism. And that's exactly what was seen: That in patients who had tumors with deficiency in the DDR pathway, in the DNA damage repair pathway, their magnitude of benefit was higher with sacituzumab govitecan as compared to those patients who didn't have tumors with damage in this pathway.

The question is, should it be used in clinical practice? Not yet, because in both the subgroups, the benefit was higher with sacituzumab govitecan as compared to standard chemotherapy. So these are interesting findings, which require further investigation and could have implications for the future. But for now, the approval of sacituzumab govitecan is for patients with hormone receptor–positive, HER2-negative breast cancer, regardless of the biomarker, regardless of Trop-2 expression.

How do these newest data build upon what we already know of sacituzumab govitecan’s utility in breast cancer?

I think these biomarker results show that we have to look at both the target of the antibody as well as target of the payload in order to fully appreciate the efficacy of these antibody-drug conjugates. And in the future, as we start comparing one ADC to another, we'll have to again look at these biomarkers and see if we can identify a population that would really derive a higher benefit with these ADCs as compared to another ADC, because the ADCs come in different flavors—some targeting Trop-2, some targeting HER2, some with similar payloads. We really have to understand the construct of the ADC and biomarkers linked to that.

References

1. Bardia A, Zhang Y, Marmé F, et al. Genomic alterations in DNA damage response (DDR) genes in HR+/HER2- metastatic breast cancer (mBC) and impact on clinical efficacy with sacituzumab govitecan (SG): Biomarker results from TROPICS-02 study. Presented at: ASCO 2024; May 31-June 2, 2024; Chicago, IL. Abstract 1075. https://meetings.asco.org/abstracts-presentations/233630

2. Study of sacituzumab govitecan-hziy versus treatment of physician's choice in participants with HR+/HER2- metastatic breast cancer (TROPiCS-02). ClinicalTrials.gov. Updated November 18, 2023. Accessed June 1, 2024. https://clinicaltrials.gov/study/NCT03901339