Sacituzumab govitecan proves real-world survival benefits in metastatic breast cancer

A real-world study of the antibody-drug conjugate (ADC) sacituzumab govitecan in patients with HR+/ HER2- metastatic breast cancer (mBC) or metastatic triple-negative breast cancer (mTNBC) shows consistent survival outcomes as those seen in clinical trials.

“Among mTNBC patients, those who received fewer lines of prior chemotherapy had longer overall survival (OS), and HER2-low status was significantly associated with OS,” said lead study author Dr Akshara Raghavendra, Department of Breast Medical Oncology, University of Texas MD Anderson Cancer Center, Houston, Texas, US.

Raghavendra and her team identified a total of 472 patients (median age 51 years) with HR+/HER2- mBC or mTNBC who received sacituzumab govitecan between 2020 and 2024. They then compared OS by breast cancer subtype, treatment history, time to next treatment (TTNT), and HER2-low status, as well as explored factors associated with OS. The median follow-up time was 9.1 months.

Of the patients, 292 (62 percent) had HER2-low status at any time, and 184 (39 percent) had HER2-0 tumours. Most of the patients (n=396, 84 percent) had previously received one or more therapy in the metastatic setting, including chemotherapy (95 percent), while about a third (n=160, 34 percent) had been treated with three or more lines of therapy. [SABCS 2025, abstract PS1-09-19]

Eighty-seven (74 percent) of 118 HR+/HER2- mBC patients had previously received ≥3 lines of therapy. Among 354 patients with mTNBC, 133 (38 percent) had received prior immune checkpoint inhibitor (ICI) therapy, and 73 (21 percent) had been treated with ≥3 lines of prior therapy.

Survival outcomes

All patients had a median OS of 15.3 months (95 percent confidence interval [CI], 13.5‒17.5), while those with HR+/HER2- mBC and mTNBC had 12.1 (95 percent CI, 8.6‒14.9) and 16.5 (95 percent CI, 13.6‒21.3) months, respectively.

Patients who had primary HR+ status (hazard ratio [HR], 1.31, 95 percent CI, 1.00‒1.71; p=0.052), received anthracycline therapy in metastatic setting (HR, 1.51, 95 percent CI, 1.05‒2.18; p=0.027), and ≥3 prior lines of treatment (HR, 1.49, 95 percent CI, 1.13‒1.96; p=0.004) were more likely to have worse OS. Survival outcomes based on age, race, or prior ICI therapy did not significantly differ.

The median TTNT was 5.9 months for 223 evaluable patients, of whom 49.3 percent had a TTNT ≥6 months. Those with a TTNT ≥6 vs <6 months tended to have received ADCs as a subsequent line of treatment (30 percent vs 14 percent; p>0.001).

The median OS in 223 patients evaluable for TTNT was 16.4 months (95 percent CI, 13.7‒20.3), while that for HR+/HER2- mBC and mTNBC patients was 19.9 months (95 percent CI, 10.2-not estimable) and 16.4 months (95 percent CI, 13.6‒20.3), respectively. Notably, HER2-low status at any time point correlated with improved OS (HR, 0.68, 95 percent CI, 0.48‒0.98; p=0.036).

“TTNT ≥6 months was an independent predictor of improved survival outcomes, reinforcing its value as a pragmatic real-world surrogate for treatment benefit and disease control,” Raghavendra said.

“Prior therapy, including immunotherapy, did not impact OS, suggesting tumour biology and treatment sequencing may be more influential,” she added.