Aditya Bardia, MD, MPH of Dana-Farber Cancer Institute speaks about ESMO 20 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).
Standard of care (SOC) chemotherapy in pts with pretreated mTNBC is associated with poor objective response rates (ORRs) and limited median progression-free survival (mPFS). SG (TRODELVYTM) is a first-in-class antibody-drug conjugate (ADC) consisting of an anti-Trop-2 antibody attached to the irinotecan active metabolite, SN-38, through a specific hydrolysable linker that allows intracellular and tumor microenvironment (bystander effect) release of SN-38. SG demonstrated 33 percent ORR and an mPFS of 5.5 months (mo) in pts with mTNBC with manageable protection in phase I / II IMMU-132-01 trial, leading to accelerated US FDA approval of SG. To validate those findings, the randomized phase III ASCENT analysis was initiated.
In the ASCENT (NCT02574455) report, pts with mTNBC who had relapsed / refractory disease after ⁇ 2 previous advanced/metastatic chemotherapy (prior taxane required) were randomized 1:1 to receive either SG (10 mg/kg IV on d 1, 8 every 21 d) or single-agent TPC (capecitabine, eribulin, vinorelbine, or gemcitabine) before progression / unacceptable toxicity of the disease. The primary endpoint was PFS, measured in the brain metastases-negative population (BMneg) by central analysis per RECIST v1.1. Overall survival (OS), ORR RECIST v1.1, and protection were the primary secondary endpoints.
BMneg was 468 out of 529 pts enrolled (median era, 54 y; median preceding lines, 4). SG (n=235) substantially increased the mPFS (5.6 vs 1.7 mo; HR, 0.41; P<0.0001) and the median OS (12.1 vs 6.7 mo; HR, 0.48; P<0.0001) relative to TPC (n=233). For SG versus 5 percent for TPC (P<0.0001), ORR was 35 percent. Neutropenia (51 percent vs 33 percent), diarrhea (10.5 percent vs < 1 percent), anemia (8 percent vs 5 percent), and febrile neutropenia (6 percent vs 2 percent) were primary treatment-related grade 3 adverse events with SG (n=258) vs TPC (n=224) in the safety population (pts receiving ⁇ 1 dose of study drug; n=482). No neuropathy or interstitial lung disease grade > 3 and no treatment-related deaths with SG have been reported.
ASCENT is the first phase III ADC study with a substantial increase in PFS and OS over SOC chemotherapy in pretreated mTNBC, confirming SG monotherapy's clinical activity and safety profile.
NCT02574455 Clinical Trial Recognition.