Maryam B. Lustberg, MD, MPH

Maryam B. Lustberg, MD, MPH, Chief of Breast Medical Oncology at Yale Cancer Center, New Haven, shared her thoughts on TROPiCS-02 with The ASCO Post.

“The progression-free survival and overall survival results of the phase III TROPiCS-02 trial position sacituzumab govitecan-hziy as an important option for patients living with hormone receptor–positive breast cancer who have previously experienced disease progression on endocrine-based therapy and at least two additional systemic therapy options. This indication is currently under Priority Review by the U.S. Food and Drug Administration,” Dr. Lustberg noted.

“The post hoc exploratory analysis presented at the 2022 San Antonio Breast Cancer Symposium¹ showed Trop-2 expression levels are not predictive of response to sacituzumab govitecan and that responses can be observed across all expression levels. Thus, Trop-2 expression levels should not be used to select for patients most likely to benefit from sacituzumab govitecan. Similarly, in the pivotal ASCENT trial in patients with triple-negative breast cancer,² Trop-2 expression levels were high in most tumors, precluding definitive conclusions about a lack of benefit in tumors with lower Trop-2 expression levels,” she said.

In addition to sacituzumab govitecan, patients with HER2-low tumors (immunohistochemistry 1+ 2+ and fluorescent in situ hybridization–negative) have the option of treatment with an alternative antibody-drug conjugate—fam-trastuzumab deruxtecan-nxki (T-DXd)—which is currently approved for patients who have received prior chemotherapy in the metastatic setting, based on the results of DESTINY-04,³ she pointed out.

“Although the optimal sequencing of sacituzumab govitecan vs T-DXd is being debated within the oncology community, both are important options for patients with metastatic hormone receptor–positive and triple-negative tumors that have low HER2 expression levels. Given that these two antibody-drug conjugates use topoisomerase I inhibitor payloads, studies are needed to determine whether there is benefit for one of these agents after a cancer has progressed over the other,” Dr. Lustberg said.

“Although Trop-2 expression levels were not shown to be predictive of benefit with sacituzumab govitecan, ongoing research will continue to evaluate innovative prognostic and predictive biomarkers. This research will allow us to offer more comprehensive personalized medicine approaches to patients living with breast cancer,” she added. 

DISCLOSURE: Dr. Lustberg has served as a consultant or advisor to AstraZeneca, Pfizer, Novartis, Seagen, and Lilly.

REFERENCES

1. Rugo HS, Bardia A, Marmé F, et al: Sacituzumab govitecan vs treatment of physician’s choice: Efficacy by Trop-2 expression in the TROPiCS-02 study of patients with HR+/HER2– metastatic breast cancer. 2022 San Antonio Breast Cancer Symposium. Abstract GS1-11. Presented December 6, 2022.

2. Bardia A, Tolaney SM, Punie K, et al: Biomarker analyses in the phase III -ASCENT study of sacituzumab govitecan versus chemotherapy in patients with metastatic triple-negative breast cancer. Ann Oncol 32:1148-1156, 2021.

3. Modi S, Jacot W, Yamashita T, et al: Trastuzumab deruxtecan in previously treated HER2-low advanced breast cancer. N Engl J Med 387:9-20, 2022.