Sacituzumab govitecan proven safe, effective in metastatic breast cancer

Treatment with sacituzumab govitecan (SG) demonstrates clinically meaningful overall survival (OS) over single-agent chemotherapy in patients with pretreated, endocrine-resistant, hormone receptor–positive/HER2-negative (HR+/HER2–) metastatic breast cancer (mBC), as confirmed by the final OS analysis from the TROPiCS-02 study, presented at ASCO 2023.

“This improvement was independent of HER2-low status,” said the researchers, led by Sara M Tolaney from the Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts, US. “This analysis reinforces SG as an effective and safe treatment for this patient population with limited treatment options.”

In this study, Tolaney and her team randomized a total of 543 eligible patients with HR+/HER2– mBC who had been previously treated with taxane, endocrine therapy (ET), CDK4/6 inhibitor, and 2 to 4 prior lines of chemotherapy to receive either SG (10 mg/kg IV d1 and 8, every 21 days; n=272) or treatment of physician’s choice (TPC; n=271) until disease progression or unacceptable toxicity.

Progression-free survival by blinded independent central review per RECIST v1.1 was the primary endpoint. Secondary endpoints included OS and safety. In an exploratory analysis, Tolaney and colleagues assessed OS by HER2 immunohistochemistry (IHC).

At data cutoff on 1 December 2022, OS events occurred in 437 patients (median follow-up 12.75 months), with 47 (8.7 percent) deaths in the SG and TPC groups (22 vs 25 deaths, respectively) since the second planned interim analysis. [ASCO 2023, abstract 1003]

Continued OS benefit

In the extended follow-up, improved OS persisted for SG relative to TPC (median, 14.5 vs 11.2 months; hazard ratio [HR], 0.79, 95 percent confidence interval [CI], 0.65‒0.95; nominal p=0.01). The OS rates for SG compared with TPC were 60.9 percent vs 47.1 percent at 12 months, 39.2 percent vs 31.7 percent at 18 months, and 25.6 percent vs 21.1 percent at 24 months.

Of the patients, 92 percent were evaluable for HER2 status by IHC (HER2 IHC0, n=217; HER2-low, n=283). SG continued to demonstrate better OS than TPC in the HER2 IHC0 (median, 13.6 vs 10.8 months; HR, 0.86, 95 percent CI, 0.63‒1.13) and HER2-low (median, 15.4 vs 11.5 months; HR, 0.74, 95 percent CI, 0.57‒0.97) groups.

“Treatment of HR+/HER2– mBC includes sequential ET combined with targeted agents followed by sequential single-agent chemotherapy, which is associated with poor outcomes and quality of life,” the researchers said.

“SG is a Trop-2–directed antibody-drug conjugate approved in multiple countries for patients with metastatic triple-negative breast cancer who received ≥1 prior systemic therapy and in the US for [those] with pretreated HR+/HER2- mBC,” they noted.

In the phase III TROPiCS-02 study, treatment with SG resulted in a statistically significant OS benefit compared with TPC in patients with pretreated ET-resistant HR+/HER2– mBC at the second planned interim OS analysis, with 390 events (median, 14.4 vs 11.2 months, respectively; HR, 0.79, 95 percent CI, 0.65-0.96; p=0.02). [ESMO 2022, abstract LBA76]