Dr. Aditya Bardia on the Latest TROPiCS-02 Analysis Data from ASCO 2024

At the 2023 American Society of Clinical Oncology (ASCO) Annual Meeting, sacituzumab govitecan-hziy (Trodelvy) continued to show overall survival (OS) benefit in patients with pretreated, endocrine-resistant, hormone receptor (HR)–positive, HER2-negative metastatic breast cancer, according to final OS results from the phase 3 TROPiCS-02 study (NCT03901339).¹

At this year's meeting, researchers presented a biomarker analysis of genomic alterations in DNA damage response (DDR) genes. Researchers were interested in whether tumors with weakened DDR mutations would respond better to sacituzumab govitecan treatment due to a phenomenon called synthetic lethality.

The analysis looked at genetic data from a subset of patients from the TROPiCS-02 study. They found that while saciuzumab govitecan benefited all patients compared to the control group, patients with DDR mutations seemed to have an even greater improvement in progression-free survival (PFS) and OS. This suggests that sacituzumab govitecan might work better in tumors with compromised DNA repair.

The study authors recommend further research to explore how the agent might work with other drugs that target the DNA repair pathway, potentially leading to even more effective treatments for this type of breast cancer.

Here, Aditya Bardia, MD, MPH, professor in the Department of Medicine, Division of Hematology/Oncology and director of translational research integration at UCLA Health, who presented the findings at the 2024 ASCO meeting, dicusses the analysis and next steps.

Transcription:

0:05 | TROPiCS-02 was a randomized phase 3 trial looking at a Trop-2 directed antibody-drug conjugate, sacituzumab govitecan, vs chemotherapy of physicians' choice for patients with hormone receptor-positive, HER2-negative metastatic breast cancer. And 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-I. So the question was if there is damage in the DNA repair pathway, or DDR, would that predict for more benefit with sacituzumab govitecan based on the mechanism?

0:56 | 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 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 sacituzumag govitecan for patients with hormone receptor-positive, HER2-negative breast cancer regardless of the biomarker, regardless of Trop-2 expression.