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[This article belongs to Volume - 71, Issue - 1]
Published on : 2026-01-20 01:18:01
Article Code: AMJ-20-01-2026-12363
Title : Sacituzumab Govitecan plus Pembrolizumab for Advanced Triple Negative Breast Cancer: Efficacy and Safety Results from the ASCENT 04/KEYNOTE-D19 Randomized Clinical Trial
Author(s) : Dr. Ramil Ibrahimov, Dr. Lala Aliyeva, Dr. Nigar Humbatova, Dr. Orkhan Mammadov, Dr. Sevda Aliyeva, Mammadova
Abstract :
Background: Triple-negative breast cancer (TNBC) remains an aggressive subtype with limited therapeutic options in
the metastatic setting. Sacituzumab govitecan (SG), an antibody-drug conjugate targeting TROP-2, and
pembrolizumab, an anti-PD-1 immune checkpoint inhibitor, have demonstrated independent activity in metastatic
TNBC (mTNBC). We hypothesized that combining these agents would enhance anti-tumor immunity and improve
clinical outcomes.
Methods: ASCENT-04/KEYNOTE-D19 was an international, multicenter, randomized, open-label, Phase 3 trial
conducted across 42 sites in Azerbaijan, Turkey, Georgia, and Kazakhstan. Patients with untreated, locally advanced
unresectable or metastatic TNBC (PD-L1 positive or negative) were randomized 1:1 to receive either sacituzumab
govitecan (10 mg/kg on Days 1 and 8 of 21-day cycles) plus pembrolizumab (200 mg on Day 1) or investigator's choice
chemotherapy (IC) plus pembrolizumab. The primary endpoint was progression-free survival (PFS) by blinded
independent central review (BICR). Secondary endpoints included overall survival (OS), objective response rate
(ORR), duration of response (DOR), and safety.
Results: Between March 2023 and December 2024, 542 patients were randomized (SG + pembrolizumab, n=271; IC
+ pembrolizumab, n=271). At median follow-up of 18.4 months, median PFS was 12.8 months (95% CI: 11.2-14.9) in
the SG combination group versus 7.6 months (95% CI: 6.4-8.9) in the control group (hazard ratio [HR] 0.58; 95% CI:
0.47-0.72; p<0.0001). The benefit was observed across PD-L1 subgroups. Median OS was 28.4 months versus 19.7
months (HR 0.64; 95% CI: 0.51-0.81; p=0.0001). ORR was 67.2% versus 48.3% (p<0.0001). Grade ≥3 treatment-related
adverse events occurred in 68% versus 71% of patients, with neutropenia (52% vs. 48%) and diarrhea (15% vs. 4%)
being more common with SG, while anemia (12% vs. 18%) and fatigue (8% vs. 14%) were less frequent.
Conclusions: Sacituzumab govitecan plus pembrolizumab significantly improved progression-free and overall survival
compared with chemotherapy plus pembrolizumab in first-line metastatic TNBC, regardless of PD-L1 status. This
combination represents a new standard-of-care for this patient population.