KEY TAKEAWAYS
- A Phase III TROPiCS-02 trial compared efficacy of SG to physician’s choice chemotherapy in endocrine-resistant, HR+/HER2- breast cancer.
- The primary aim was to evaluate the PFS through a blinded independent central review.
- SG showed a 34% decrease in the likelihood of progression or mortality with a median PFS of 5.5 months versus 4.0 months with chemotherapy.
- The study included patients with limited treatment alternatives who had already been heavily treated with a history of cyclin-dependent kinase 4/6 inhibitor use.
- The median overall survival during the first planned interim analysis was not yet mature, with a hazard ratio of 0.84 and a P value of 0.14.
- SG showed significant PFS benefit over chemo with manageable safety in heavily pretreated, endocrine-resistant HR+/HER2- metastatic breast cancer.
Metastatic breast cancer that is resistant to endocrine therapy and is positive for hormone receptors (HR+) but negative for human epidermal growth factor receptor 2 (HER2-) is conventionally managed with sequential administration of single-agent chemotherapy, which has been associated with suboptimal clinical outcomes. Sacituzumab govitecan (SG) is an antibody-drug conjugate that targets trophoblast cell-surface antigen 2, an epithelial antigen expressed in breast cancer. It contains an SN-38 payload and is considered a first-in-class medication. In this randomized phase III study conducted on a global scale, the efficacy of SG was compared to that of physician’s choice chemotherapy (eribulin, vinorelbine, capecitabine, or gemcitabine) in patients with endocrine-resistant, chemotherapy-treated HR+/HER2- locally recurrent inoperable or metastatic breast cancer. The principal objective was to evaluate progression-free survival (PFS) through a blinded independent central review.
The study randomly allocated patients into SG (n = 272) and chemotherapy (n = 271). The cohort exhibited a median age of 56 years, with 95% presenting with visceral metastases and 99% having a history of cyclin-dependent kinase 4/6 inhibitor use. The median number of chemotherapy lines for the advanced disease was three. The primary endpoint demonstrated a 34% decrease in the likelihood of progression or mortality (hazard ratio, 0.66 [95% CI, 0.53 to 0.83; P = .0003]). The median progression-free survival (PFS) was 5.5 months (95% confidence interval [CI], 4.2 to 7.0) with SG and 4.0 months (95% CI, 3.1 to 4.4) with chemotherapy. The PFS at 6 and 12 months was 46% (95% CI, 39 to 53) versus 30% (95% CI, 24 to 37) and 21% (95% CI, 15 to 28) versus 7% (95% CI, 3 to 14), respectively. The median overall survival during the first planned interim analysis was not yet mature, with a hazard ratio of 0.84 and a P value of 0.14. The prominent grade ≥ 3 adverse events related to treatment, comparing SG versus chemotherapy, were neutropenia (51% versus 38%) and diarrhea (9% versus 1%). The study showed that SG exhibited a notable progression-free survival advantage compared to chemotherapy in patients with advanced breast cancer who were heavily treated, endocrine-resistant, HR+/HER2- and had limited treatment alternatives. Additionally, SG had an acceptable safety profile.
Source: https://pubmed.ncbi.nlm.nih.gov/36027558/
Clinical Trail: https://clinicaltrials.gov/ct2/show/NCT03901339
Rugo HS, Bardia A, Marmé F, Cortes J, Schmid P, Loirat D, Trédan O, Ciruelos E, Dalenc F, Pardo PG, Jhaveri KL, Delaney R, Fu O, Lin L, Verret W, Tolaney SM. Sacituzumab Govitecan in Hormone Receptor-Positive/Human Epidermal Growth Factor Receptor 2-Negative Metastatic Breast Cancer. J Clin Oncol. 2022 Oct 10;40(29):3365-3376. doi: 10.1200/JCO.22.01002. Epub 2022 Aug 26. PMID: 36027558.
