The first-in-class antibody–drug conjugate sacituzumab govitecan significantly improved progression-free survival (PFS) and overall survival (OS) over standard chemotherapy in the phase III ASCENT study in patients with advanced metastatic triple-negative breast cancer (TNBC), as reported in the Late-Breaking presentation today at ESMO Virtual Congress 2020 (LBA17).
Sacituzumab govitecan comprises an anti-Trop-2 antibody coupled to SN-38, the active metabolite of irinotecan, via a unique hydrolysable linker, which subsequently enables the intracellular release of SN-38 leading to bystander effects within the tumour microenvironment. The global, open-label, randomised ASCENT study was conducted across the US, Canada and Europe to support the accelerated approval of sacituzumab govitecan by the US FDA following promising phase I/II results. The study compared sacituzumab govitecan (10 mg/kg IV) with single-agent TPC (capecitabine, eribulin, vinorelbine or gemcitabine) in 468 patients with relapsed/refractory TNBC who were negative for brain metastases after two or more prior chemotherapies (including a taxane) for metastatic disease.
Median PFS by central review – the primary endpoint – was significantly longer with sacituzumab govitecan (5.6 months) versus TPC (1.7 months; hazard ratio [HR] 0.41; p<0.0001). Secondary efficacy endpoints were also significantly improved with the antibody–drug conjugate. Median OS was 12.1 months with sacituzumab govitecan compared with 6.7 months with TPC (HR 0.48; p<0.0001), and objective response rates were 35% and 5%, respectively (p<0.0001). Safety was as expected from earlier trials, and treatment-related grade ≥3 adverse events with sacituzumab govitecan versus TPC included neutropenia (51% versus 33%), diarrhoea (10% versus <1%), leukopenia (10% versus 5%) and febrile neutropenia (6% versus 2%). No deaths related to treatment with sacituzumab govitecan were reported.
For the first time, the results of the ASCENT study demonstrate significant improvements in survival measures with tailored treatment over standard treatment in patients with TNBC. These landmark results advance the treatment paradigm for this notoriously difficult-to-treat patient population who until now had limited treatment options beyond standard chemotherapy.
Abstract and session details:
- Bardia A et al. ASCENT: A randomized phase 3 study of sacituzumab govitecan (SG) vs treatment of physician’s choice (TPC) in patients (pts) with previously treated metastatic triple-negative breast cancer (mTNBC). ESMO Virtual Congress 2020, LBA17
Proffered Paper - Breast cancer, metastatic, 19.09.2020, h. 16:20 – 18:00, Channel 1
ESMO 2020 Highlights on sacituzumab govitecan in metastatic TNBC: The ASCENT study