Expert Point of View: William Gradishar, MD

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William Gradishar, MD, the Betsy Bramsen Professor of Breast Oncology at Northwestern University Feinberg School of Medicine and Deputy Director for the Clinical Network of the Lurie Cancer Center, commented on the findings of the ASCENT biomarker analysis in the closing panel discussion.

The primary analysis found sacituzumab govitecan yielded improvements in progression-free survival, overall survival, and response rate, compared with physician’s choice of chemotherapy.1 The current report, presented by Sara A. Hurvitz, MD, was an exploratory biomarker analysis focusing on levels of Trop-2, thought possibly to be important since sacituzumab govitecan binds to Trop-2.2

William Gradishar, MD

William Gradishar, MD

Trop-2 Expression and BRCA Germline Mutation

Specifically, the biomarker analysis asked questions that have often been raised: Does the level of Trop-2 expression impact the likelihood of benefiting from sacituzumab govitecan? Are patients with low Trop-2 expression less likely to respond and those with higher levels more likely to respond?

The analysis showed that not only was median progression-free survival—the study’s primary endpoint—higher in patients who received sacituzumab govitecan compared with those who received their physician’s choice of therapy, but this was true across all subgroups of Trop-2 expression. The magnitude of benefit was, however, greatest at the highest expression level, diminishing as Trop-2 levels dropped. With the caveat that patient subsets are small, he added, “There is no doubt there is a relative degree of benefit” by Trop-2 expression.

The investigators also examined outcomes according to the presence or absence of a germline BRCA mutation. Again, “although equally shaky” due to small subsets (34 BRCA-positive patients), Dr. Gradishar said, the advantage of sacituzumab govitecan was clear regardless of mutation status, “though it’s more so for BRCA-negative patients in each category.”

Clinical Implications

“In my own view, what the data tell me right now, is not to use Trop-2 expression as a way of discriminating who should get sacituzumab govitecan,” Dr. Gradishar concluded. “If we have other alternative treatments in this space…or we have competing results suggesting another option is better … then maybe we should be looking at Trop-2 expression. But for now, I’m not sure I would argue for its use in making treatment decisions regarding sacituzumab govitecan because it works across all groups.” 

DISCLOSURE: Dr. Gradishar disclosed industry relationships with AstraZeneca, Carrick Therapeutics, Celltrion, Genentech, Genomic Health, MacroGenics, Merck, Pfizer, and Seattle Genetics.


1. Bardia A, Tolaney SM, Loirat D, et al: ASCENT: A randomized phase III study of sacituzumab govitecan vs treatment of physician’s choice in patients with previously treated metastatic triple-negative breast cancer. ESMO Virtual Congress 2020. Abstract LBA17. Presented September 19, 2020.

2. Hurvitz SA, Tolaney SM, Punie K, et al: Biomarker evaluation in the phase 3 ASCENT study of sacituzumab govitecan versus chemotherapy in patients with metastatic triple-negative breast cancer. 2020 San Antonio Breast Cancer Symposium. Abstract GS3-06. Presented December 10, 2020.


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