Sacituzumab Govitecan Improved Outcomes in HR+/HER2– Metastatic Breast Cancer Vs Physician’s Choice

Results from a post-hoc subgroup analysis of the phase 3 TROPiCS-02 study indicated that sacituzumab govitecan improved efficacy outcomes vs physician’s choice of treatment in HER2-low and HER2 immunohistochemistry 0, hormone receptor–positive metastatic breast cancer.

Regardless of HER2 immunohistochemistry (IHC) status, sacituzumab govitecan (Trodelvy) appeared to be an effective treatment option for patients with hormone receptor–positive, HER2-negative metastatic breast cancer, according to results from a post-hoc subgroup analysis of the phase 3 TROPiCS-02 study (NCT03901339)1 that were presented at the 2022 European Society for Medical Oncology (ESMO) Congress.

The analysis assessed the efficacy of sacituzumab govitecan vs physician’s choice in several subgroups including the HER2-low, HER2 IHC0, and intent-to-treat (ITT) populations. In the HER2-low population, median progression-free survival (PFS) was 6.4 months with the sacituzumab govitecan regimen vs 4.2 months in the physician’s choice arm (Hazard ratio [HR], 0.58; 95% CI, 0.42-0.79; P <.001). For those with HER2 IHC0 disease, the median PFS was 5.0 months with sacituzumab govitecan vs 3.4 months for physician’s choice (HR, 0.72; 95% CI, 0.51-1.00; P = .05). In the ITT arm, the median PFS for those in the sacituzumab govitecan cohort was 5.5 months vs 4.0 months in the physician’s choice cohort (HR, 0.66; 95% CI, 0.53-0.83; P = .0003).

Investigators also assessed overall response rate (ORR) by HER2 status. The ORR was 26% (n = 38/149) for sacituzumab govitecan compared with 12% (n = 16/134) for physician’s choice in the HER2-low group (Odds ratio [OR], 2.52; 95% CI, 1.33-4.78). In the HER2 IHC0 group, the ORR was 16% (n = 16/101) and 15% (n = 17/116) for sacituzumab govitecan and physician’s choice, respectively. In the ITT population, the ORR was 21% (n = 57/272) and 14% (n = 38/271) in each respective arm.

A total of 543 patients enrolled on the TROPiCS-02 study and were randomly assigned 1:1 to received either the experimental arm (n = 272) or the control arm (n = 271). The study included patients with hormone receptor–positive/HER2-negative metastatic or locally recurrent inoperable breast cancer and who had undergone treatment with 2 to 4 previous lines chemotherapy for metastatic breast cancer. Patients received either 10 mg/kg of intravenous sacituzumab govitecan on days 1 and 8 every 21 days or physician’s choice of capecitabine (Xeloda), vinorelbine (Navelbine), gemcitabine (Gemzar), or eribulin (Halaven) until unacceptable toxicity or disease progression.

The primary end point was PFS, with key secondary end points including overall survival (OS), ORR, duration of response, clinical benefit rate, patient-reported outcomes, and safety.

In total, 52% of patients were HER2-low and 40% were HER2 IHC0. Moreover, 92% of patients were evaluable for HER2 by IHC testing. Baseline demographics and patient characteristics across the HER2-low, HER2 IHC0, and ITT populations were comparable.

In terms of safety, 74% of those in the HER2-low group receiving sacituzumab govitecan experienced grade 3 or higher treatment-emergent adverse effects (TEAEs) compared with 59% in the physician’s choice arm. Moreover, 71% of those in the HER2 IHC0 group treated with sacituzumab had high-grade TEAEs vs 62% in the control group. Grade 3/4 TEAEs occurred in 74% and 60% of those in the overall safety population across both respective cohorts. The analysis concluded that the safety profile of sacituzumab govitecan in the HER2-low and HER2 IHC0 groups was generally manageable and consistent with that of the TROPiCS-02 ITT population.


Schmid P, Cortés J, Marmé F, et al. Sacituzumab govitecan (SG) efficacy in hormone receptor-positive/human epidermal growth factor receptor 2-negative (HR+/HER2–) metastatic breast cancer (MBC) by HER2 immunohistochemistry (IHC) status in the phase III TROPiCS-02 study. Ann Oncol. 2022;33(suppl 7):S88-S121. doi:10.1016/annonc/annonc1040