Efficacy and Safety from the ASCENT Study

Sacituzumab govitecan-hziy (SG) is a first-in-class antibody and topoisomerase inhibitor conjugate targeting Trop-2, a compelling target in patients with metastatic triple-negative breast cancer (mTNBC). SG is indicated in unresectable locally advanced or mTNBC patients who have received ≥2 prior systemic therapies, ≥1 being for metastatic disease.¹ SG showed positive efficacy results from the phase 3 ASCENT study and demonstrated a statistically significant and clinically meaningful 59% reduction in the risk of disease worsening or death (hazard ratio, 0.41; 95% confidence interval, 0.32-0.52; P <.001).² The key takeaways from the study were that patients in the SG group lived longer with less disease progression and had more tumors that reduced in size or disappeared.³

ASCENT was a phase 3 trial with mTNBC patients designed to validate the efficacy and safety of SG observed in an earlier phase 2 study of heavily pretreated patients with mTNBC.⁴ Results from ASCENT warranted early trial cessation and were the basis for the FDA’s accelerated approval of SG for mTNBC, a disease with few other treatment options.⁴ The primary end point for the study was progression-free survival. The ASCENT study began in November 2017 and ended in March 2020. A total of 529 patients with mTNBC enrolled, and patients were randomized into an SG arm or an arm that received chemotherapy chosen by the physician (either eribulin, vinorelbine, capecitabine, or gemcitabine).³

Patients in the SG group experienced more side effects than patients in the chemotherapy group.³ Safety was assessed in any patient who received ≥1 doses of medication, SG or chemo.³ This resulted in a safety analysis of 258 patients receiving SG and 224 patients receiving chemo. The most common side effects of SG were neutropenia, diarrhea, nausea, alopecia, fatigue, and anemia.³ Neutropenia was managed by reducing or delaying treatment; oral antidiarrhea medication, such as loperamide, was used to manage patients who developed diarrhea; and nausea was managed by prompt symptomatic intervention through growth factor support and medication to treat nausea and vomiting.³ There were no treatment-related deaths in the SG group.³

ASCENT results were so compelling, the decision was made to halt the study early.⁴ The fast-track FDA approval enabled SG to be included in the National Comprehensive Cancer Network Breast Cancer Guidelines soon after approval.⁵ FDA approval of SG for mTNBC and its addition into the National Comprehensive Cancer Network Breast Cancer Guidelines has provided breast cancer patients and breast cancer oncology teams with another tool to use against a devastating disease.

References

1. Trodelvy (sacituzumab govitecan-hziy) [package insert]. Foster City, CA: Gilead Sciences, Inc; April 2021.
2. Bardia A, Hurvitz SA, Tolaney SM, et al. Sacituzumab govitecan in metastatic triple-negative breast cancer. N Engl J Med. 2021;384:1529-1541.
3. Bardia A, Hurvitz SA, Rugo HS, et al. A plain language summary of the ASCENT study: sacituzumab govitecan for metastatic triple-negative breast cancer. Future Oncol. 2021;17:3911-3924.
4. Cancer Network. Phase III ASCENT study of metastatic TNBC halted due to compelling efficacy. Updated April 2020. www.cancernetwork.com/view/phase-iii-ascent-study-metastatic-tnbc-halted-due-compelling-efficacy. Accessed December 1, 2021.
5. Gilead. Gilead statement on new NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines) recommendation for sacituzumab govitecan-hziy (Trodelvy) in second-line and later metastatic triple-negative breast cancer. Updated September 2021. www.gilead.com/news-and-press/company-statements/gilead-statement-on-new-nccn-clinical-practice-guidelines-in-oncology-nccn-guidelines-recommendation-for-sacituzumab-govitecan-hziy-trodelvy-in-second-line-and-later-metastatic-triple-negative-breast-cancer. Accessed December 1, 2021.