Final Results from the Phase 3 ASCENT Study: Sacituzumab Govitecan versus TPC in Patients with Previously Treated, Metastatic TNBC

Treatment goals in patients with metastatic breast cancer include extended survival and enhanced quality of life (QOL). Investigators presented the final data on SG efficacy, including progression-free survival (PFS) and overall survival (OS), and safety and QOL findings after additional follow-up, in the ASCENT trial.

SG is an antibody–drug conjugate containing an anti–Trop-2 antibody linked to the cytotoxic SN-38 payload via a hydrolyzable linker. SG is approved by the US Food and Drug Administration for patients with metastatic triple-negative breast cancer (mTNBC) who have received ≥2 previous chemotherapies, with >1 in the metastatic setting. Patients with mTNBC were randomly assigned to receive SG (10 mg/kg intravenously on days 1 and 8, every 21 days) or TPC (capecitabine, eribulin, vinorelbine, or gemcitabine) until disease progression or unacceptable toxicity. The primary end point was PFS in patients without known brain metastases at baseline. OS, safety, and health-related QOL were critical secondary end points. Patients who received ≥1 doses of SG on either arm were evaluated for safety.

At the start of the study, 468 of the 529 enrolled patients had no known brain metastases (median age, 54 years [range, 27-82 years]; median previous lines of therapy, 4 [range, 2-17]). Compared with TPC (n = 233), SG (n = 235) had significantly better median PFS (5.6 vs 1.7 months; hazard ratio [HR], 0.39; P = .0001) and median OS (12.1 vs 6.7 months; HR, 0.48; P = .0001) at the final database lock. At 24 months, OS in the SG cohort was 22.4% (95% confidence interval [CI], 16.8%-28.5%) versus only 5.2% in the TPC group (95% CI, 2.5%-9.4%). In the safety population, 482 patients received ≥1 doses of treatment. The most common treatment-related grade ≥3 adverse events with SG (n = 258) versus TPC (n = 224) were diarrhea (11% vs 0.4%), neutropenia (52% vs 33%), anemia (8% vs 5%), and febrile neutropenia (6% vs 2%), respectively. Investigators reported 1 case of grade 3 interstitial lung disease and no grade ≥3 neuropathy with SG. The TPC group had 1 treatment-related mortality owing to neutropenic sepsis, whereas the SG group had no treatment-related deaths. In both groups, treatment termination due to adverse events was ≤3%. All 5 primary focus health-related QOL domains revealed clinically relevant and significant improvements in the SG arm compared with the TPC arm.

Data analysis after ASCENT’s final database lock confirms improved survival outcomes accorded by SG compared with single-agent chemotherapy, with a tolerable safety profile and improved QOL for patients with mTNBC in the post–second-line treatment setting. These findings support SG as a feasible therapy option for this patient group.

Source

Bardia A, Tolaney SM, Loirat D, et al. Sacituzumab govitecan (SG) versus treatment of physician’s choice (TPC) in patients (pts) with previously treated, metastatic triple-negative breast cancer (mTNBC): final results from the phase 3 ASCENT study. J Clin Oncol. 2022;40:16. Abstract 1071.