Second-line sacituzumab govitecan improves survival in metastatic TNBC

In pretreated metastatic TNBC patients, standard of care chemotherapy is associated with low objective response rates (ORRs) and short median progression-free survival (PFS). Results of the phase 3 ASCENT trial show improved ORR rates, and improved survival.

Sacituzumab govitecan is an antibody-drug conjugate composed of an anti-Trop-2 antibody coupled to SN-38, the active metabolite of irinotecan. Trop-2 is expressed in all subtypes of breast cancer and linked to a poor prognoses. SN-38 is released both intracellularly and in the tumour microenvironment. Based on the results of a phase 1/2 trial, the FDA recently approved sacituzumab govitecan for treatment of refractory, metastatic TNBC [1].

In the phase 3 ASCENT study, 468 metastatic TNBC patients who had relapsed or had refractory disease after ≥2 prior chemotherapies in the advanced/metastatic setting were randomised 1:1 to sacituzumab govitecan (10 mg/kg IV on day 1 and 8, every 3 weeks) or single-agent chemotherapy of physicians’ choice (capecitabine, eribulin, vinorelbine, or gemcitabine) until disease progression/unacceptable toxicity [2].

Sacituzumab govitecan compared with chemotherapy significantly improved both median PFS (5.6 vs 1.7 months; HR 0.41; P<0.0001) and median overall survival (12.1 vs 6.7 months; HR 0.48; P<0.0001; see Figure). ORR was 35% for sacituzumab govitecan versus 5% for chemotherapy (P<0.0001). A benefit was observed across all subgroups.

In the safety population (n=482), treatment-related grade ≥3 adverse events were neutropenia (51% vs 33%), diarrhoea (10.5% vs <1%), anaemia (8% vs 5%), and febrile neutropenia (6% vs 2%).

Figure: Overall survival in the phase 3 ASCENT trial [2]

1. Bardia A, et al. N Engl J Med. 2019;380:741-751.
2. Bardia A. et al. ASCENT: A randomized phase III 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 2020 Virtual Meeting, abstract LBA17.