ASCENT: sacituzumab govitecan doubles survival in heavily pretreated metastatic triple-negative breast cancer
In triple-negative breast cancer that had already been through at least two treatments, the TROP2 antibody-drug conjugate sacituzumab govitecan roughly doubled the time patients lived compared with standard chemotherapy.
Open-label phase 3 trial of 529 patients with relapsed or refractory metastatic triple-negative breast cancer after two or more prior chemotherapy regimens, randomised to sacituzumab govitecan or single-agent chemotherapy (eribulin, vinorelbine, capecitabine or gemcitabine). The primary endpoint was PFS in the 468 patients without brain metastases.
Median PFS was 5.6 vs 1.7 months (HR 0.41) and median overall survival 12.1 vs 6.7 months (HR 0.48). It converted the 2020 accelerated approval into a full approval and was the first ADC to show a survival benefit in TNBC.
- Median PFS 5.6 vs 1.7 months; HR 0.41 (95% CI 0.32-0.52).
- Median overall survival 12.1 vs 6.7 months; HR 0.48 (95% CI 0.38-0.59).
- Objective response rate 35% vs 5%.
- Grade 3 or higher neutropenia 51% vs 33% and diarrhoea 10% vs under 1%; UGT1A1 *28 homozygotes had more neutropenia.
- Benefit was seen regardless of TROP2 expression level and in patients with germline BRCA mutations.
Sacituzumab govitecan is a standard second-line or later treatment for metastatic triple-negative breast cancer, roughly doubling survival compared with the chemotherapies it was tested against. Patients should expect neutropenia and diarrhoea, which are manageable with growth factor support and loperamide. Trials are now testing it earlier, in first-line combinations with pembrolizumab and after surgery for residual disease.
- Open-label; PFS assessed by blinded review.
- The control chemotherapies were of modest efficacy in this setting (ORR 5%).
- Patients with brain metastases were excluded from the primary analysis and remain under-studied.
- The relatively unstable linker releases SN-38 systemically, which contributes to neutropenia and diarrhoea.
Pages like this
not linked directly; found by shared links- RoadmapTROP2 ADC roadmap: sacituzumab govitecan → Dato-DXd → sac-TMT → bispecifics and PET
Shares ASCENT-03, ASCENT, ASCENT-04 / KEYNOTE-D19, TROP2 PET to choose and sequence TROP2 ADCs.
- Key paperDESTINY-Breast03: trastuzumab deruxtecan beats T-DM1 as second-line treatment of HER2-positive metastatic breast cancer
Shares Sara A. Hurvitz, Javier Cortés, Payload (ADC), Topoisomerase-I inhibitors (and ADC payloads).
- PairingTROP2 PET → TROP2 ADC selection
Shares TROP2 PET to choose and sequence TROP2 ADCs, Sacituzumab govitecan, TROP2, Antibody-drug conjugate (ADC).
- RoadmapTNBC roadmap: from 'nothing to target' to ADC + immunotherapy first line
Shares ASCENT-03, ASCENT, ASCENT-04 / KEYNOTE-D19, ADC for residual disease after KEYNOTE-522.
- Key paperTROPION-Breast01: datopotamab deruxtecan versus chemotherapy in pretreated hormone-receptor-positive breast cancer, and why a PFS win did not translate to survival
Shares TROP2 PET to choose and sequence TROP2 ADCs, Topoisomerase-I inhibitors (and ADC payloads), TROP2, Overall survival (OS).
- TrialTROPiCS-02
Shares Hope S. Rugo, Sacituzumab govitecan, TROP2.
- TermProdrug
Shares Linker (ADC), Payload (ADC), Topoisomerase-I inhibitors (and ADC payloads), Antibody-drug conjugate (ADC).
- Key paperEV-302: enfortumab vedotin plus pembrolizumab replaces chemotherapy as first treatment for advanced bladder cancer
Shares Payload (ADC), Objective response rate (ORR), Overall survival (OS), Progression-free survival (PFS).