Sacituzumab govitecan demonstrated superior efficacy over chemotherapy as a treatment for patients with metastatic triple-negative breast cancer, with positive results seen in all Trop-2 expression cohorts, according to phase 3 study results published in Journal of Clinical Oncology.

Trop-2 is overexpressed in up to 90% of patients with triple-negative breast cancer, an aggressive and difficult-to-treat cancer subtype. Initial results of the ASCENT clinical trial, which evaluated the Trop-2-directed antibody-drug conjugate sacituzumab govitecan in patients with triple-negative breast cancer, gained FDA approval after initial results were reported.

In a final preplanned safety and efficacy analysis, researchers reported data from 529 patients, whom they randomly assigned to sacituzumab govitecan (n = 267) or to physician’s choice chemotherapy (n = 262). Treatment continued until disease progression or intolerable toxicity. Median follow-up was 11.2 months for patients assigned to sacituzumab govitecan and 6.3 months for patients assigned to chemotherapy.

In the intent-to-treat population, assignment to sacituzumab govitecan correlated with significant improvements in progression-free survival (PFS) and overall survival (OS).

In the Trop-2 evaluable population, assignment to sacituzumab govitecan (n = 168) improved PFS and OS at all H-Score expression levels, compared to chemotherapy (n = 150). For patients with an H-Score between 200 and 275, the median PFS and OS for sacituzumab govitecan were 4.8 months and 13.4 months, respectively, compared to 1.6 months and 6.5 months for chemotherapy.

HER2 expression was evaluable in 78% (n = 425) of the study population. The majority of patients (71%) expressed HER2 at IHC0, while the remaining evaluable patients (29%) were HER2-low. The researchers observed high levels of Trop-2 expression regardless of HER2 status.

In HER2-evaluable patients, assignment to sacituzumab govitecan (n = 211) was associated with superior PFS, OS, and objective response rate compared to chemotherapy (n = 204).

The safety analysis aligned with previously reported data. Treatment-emergent adverse events (grade ≥3) occurred in 73% of patients assigned to sacituzumab govitecan (n = 188) and 65% of patients assigned to chemotherapy (n = 145). Rates of treatment discontinuation due to adverse events were low (n = 12 in both cohorts), and the researchers observed no treatment-related deaths.

“These data reinforce sacituzumab govitecan as a standard-of-care treatment option in pretreated metastatic triple-negative breast cancer. Sacituzumab govitecan is currently recommended in major guidelines for treating patients with metastatic triple-negative breast cancer who received at least two previous therapies (≥1 in the metastatic setting) owing to the significant clinical benefit observed in the phase 3 ASCENT study.”

- Aditya Bardia, MD, MPH, FASCO, professor and director of translational research integration at UCLA Jonsson Comprehensive Cancer Center.

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Reference:

https://ascopubs.org/doi/10.1200/JCO.23.01409

https://clinicaltrials.gov/study/NCT02574455

Disclosures: Some authors declared financial ties to drugmakers. See full study for details. ASCENT was supported by Gilead Sciences.

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