Dr Jhaveri on the Implications of ASCENT-07 Data for First-Line Sacituzumab Govitecan Use in HR+, HER2– Breast Cancer

"It was a negative study at end of the day. We currently still have sacituzumab govitecan available for patients who've had at least 1 line and are not candidates in the second line for T-DXd or pretreated patients…but we cannot [recommend] using this agent instead of first-line chemotherapy based on [ASCENT-07 data].”

Komal Jhaveri, MD, FACP, section head of the Endocrine Therapy Research Program, clinical director of the Early Drug Development Service, and the Patricia and James Cayne Chair for Junior Faculty at Memorial Sloan Kettering Cancer Center, discussed the implications of data from the phase 3 ASCENT-07 trial (NCT05840211), which failed to meet its primary progression-free survival (PFS) end point with sacituzumab govitecan-hziy (Trodelvy) in the first line following endocrine therapy for patients with hormone receptor–positive, HER2-negative metastatic breast cancer.

Jhaveri began by noting that this outcome was disappointing given that the agent had previously demonstrated superiority in both PFS and overall survival (OS) in more heavily pretreated settings.Results from ASCENT-07 highlight the significant heterogeneity of hormone receptor–positive disease and how different disease settings can influence treatment outcomes, she stated.

In the study population, approximately 15% to 16% of patients had primary endocrine resistance, having progressed within 6 months of receiving a CDK4/6 inhibitor, and 24% had de novo metastatic disease, Jhaveri noted. In exploratory analyses of investigator-assessed PFS, there was a numerical increase of 2 months compared with the control arm, but this did not reach statistical significance, she added. Jhaveri explained that investigators might take patients off a trial early to offer other available therapies, such as fam-trastuzumab deruxtecan-nxki (T-DXd; Enhertu), based on clinical symptoms or tumor markers before official disease progression is met.

Despite a higher proportion of patients in the control arm receiving subsequent ADCs, an OS signal emerged with a HR that was numerically more favorable than the HR for the primary end point. However, no statistical significance could be claimed for OS due to the trial's hierarchical testing structure. Although these data do not support replacing frontline chemotherapy with sacituzumab govitecan, the agent remains a standard for patients who have received at least one prior line of therapy and are not suitable candidates for T-DXd, Jhaveri concluded.