SASCIA Phase 3 Trial Evaluating Sacituzumab Govitecan in Patients with Primary HER2-Negative Breast Cancer with High Relapse Risk

Patients with triple-negative breast cancer (TNBC) who do not have a complete pathologic response and are hormone receptor (HR)-positive, HER2-negative with a clinical, pathologic stage plus estrogen receptor status and grade score ≥3 or with 2 lymph node metastases have a high risk for recurrence.¹ Postneoadjuvant therapy can enhance survival in patients with high-risk disease.¹ Sacituzumab govitecan-hziy has shown promise in patients with pretreated metastatic TNBC and HR-positive, HER2-negative breast cancer. Previous treatment with immune checkpoint inhibitors or cyclin-dependent kinase 4/6 and mTOR inhibitors yielded these findings. The phase 3 ASCENT trial confirmed efficacy in TNBC. A phase 3 trial in an HR-positive group is now underway. According to these findings, sacituzumab govitecan could be a viable option for treating resistant residual illness after routine neoadjuvant chemotherapy.¹

SASCIA is a phase 3, multicenter, randomized study in patients with HER2-negative breast cancer with residual disease after neoadjuvant chemotherapy and at high risk for recurrence with 1:1 allocation to sacituzumab govitecan or treatment of physician’s choice.¹ In patients with HR-positive breast cancer, endocrine-based therapy will be administered according to guidelines. SASCIA will randomize 1200 patients with HER2-negative, HR-positive or HR-negative breast cancer assessed preferably on tumor tissue from postneoadjuvant residual invasive disease.¹ The original trial results where sacituzumab govitecan gained US Food and Drug Administration (FDA) approval for metastatic TNBC showed that the most common adverse events occurring in ≥25% of patients were nausea, neutropenia, diarrhea, fatigue, anemia, vomiting, alopecia, constipation, rash, decreased appetite, and abdominal pain.²

SASCIA’s primary objective will be to compare invasive disease-free survival between patients treated with sacituzumab govitecan versus treatment of physician’s choice.¹ Secondary objectives will be to compare overall survival (key secondary objective), distant disease-free survival between groups, safety, compliance, patient-reported outcomes, and patient quality of life. SASCIA is investigating the efficacy and safety of sacituzumab govitecan compared with treatment of physician’s choice in patients with HER2-negative breast cancer, at risk for recurrence. Recruitment started in December 2020 and will take an estimated 36 months (42 patients per month). As of April 21, 2021, 27 of 1200 patients have been randomized in Germany, with other international groups to follow.¹

References

1. Marmé F, Stickeler E, Furlanetto J, et al. Phase III postneoadjuvant study evaluating sacituzumab govitecan, an antibody drug conjugate in primary HER2-negative breast cancer patients with high relapse risk after standard neoadjuvant treatment: SASCIA. J Clin Oncol. 2021;39(15 suppl):Abstract TPS602.
2. Wahby S, Fashoyin-Aje L, Osgood CL, et al. FDA approval summary: accelerated approval of sacituzumab govitecan-hziy for third-line treatment of metastatic triple-negative breast cancer. Clin Cancer Res. 2021;27:1850-1854.