Sacituzumab govitecan (Trodelvy) led to increased response rates and improved progression-free survival (PFS) compared with chemotherapy in heavily pretreated patients with metastatic triple-negative breast cancer (TNBC) and stable brain metastases, according to a subgroup analysis of the phase 3 ASCENT clinical trial. The drug did not lead to improved overall survival (OS) in patients with stable brain metastases. These results were presented at the 2020 San Antonio Breast Cancer Symposium (SABCS).
“Although the sample size was small, in this exploratory analysis of very poor prognosis patients with brain metastases in ASCENT, [sacituzumab govitecan] provided numerically better responses rates and PFS, but not overall survival relative to chemotherapy,” said lead investigator Véronique Diéras, MD, Oncologist, Centre Eugène-Marquis, Rennes, France.
Sacituzumab govitecan is a novel antibody–drug conjugate comprising an anti–Trop-2 monoclonal antibody conjugated to SN-38 and a hydrolysable linker. SN-38 can cross the blood–brain barrier, making it a good candidate for central nervous system tumors.
The FDA granted accelerated approval to sacituzumab govitecan in April 2020 for the treatment of patients with metastatic TNBC who have received at least 2 previous therapies in the metastatic setting.
The ASCENT Study
The primary results of the ASCENT study were presented at the 2020 European Society for Medical Oncology meeting. At SABCS 2020, Dr Diéras presented an exploratory subgroup analysis of patients in ASCENT who had stable brain metastases.
The ASCENT clinical trial enrolled 529 patients who had metastatic TNBC who had previously received at least 2 chemotherapy regimens for advanced disease. The patients were randomized in a 1:1 ratio to either sacituzumab govitecan at 10 mg/kg intravenously on days 1 and 8 of every 3-week cycle or to chemotherapy based on the physician’s choice. Patients continued treatment until disease progression or unacceptable adverse events.
In the primary analysis of the study, the median PFS was 5.6 months with sacituzumab govitecan versus 1.7 months with chemotherapy, a significant 59% improvement favoring the antibody–drug conjugate (P <.0001). The median OS was 12.1 months versus 6.7 months, respectively (P <.0001). The objective response rate (ORR) was 35% with sacituzumab govitecan versus 5% with the physician’s choice of chemotherapy.
The subgroup analysis Dr Diéras presented at SABCS included 61 patients from ASCENT who had stable brain metastases for at least 4 weeks at trial enrollment. Of the 32 patients with brain metastases in the antibody–drug conjugate arm, 6% continued to receive treatment as of data cutoff compared with none of the patients who received chemotherapy. The primary reason for treatment discontinuation was disease progression.
The patients in the subgroup analysis had a median age of approximately 52 years. The majority were white, had ECOG performance status 1, and had no BRCA1 or BRCA2 mutations. The median number of previous regimens was 5 (range, 2-10), and a total of 43% of the patients had received a previous checkpoint inhibitor.
The ORR in the patients with brain metastases was 3% with sacituzumab govitecan versus 0% with chemotherapy, and the disease control rates were 9% and 3%, respectively. The rates of stable disease were 47% in the antibody–drug conjugate arm and 31% in the chemotherapy arm, but only 2 patients in the sacituzumab govitecan group and 1 in the chemotherapy group had stable disease lasting for more than 6 months.
The median PFS was 2.8 months with sacituzumab govitecan and 1.6 months with chemotherapy. At 3 months, the PFS rate was 41.4% with sacituzumab govitecan and 27.7% with chemotherapy. By 9 months, the PFS rates were 9% and 0%, respectively.
The median OS was 6.8 with sacituzumab govitecan and 7.5 months with the physician’s choice of chemotherapy.
No new safety concerns were raised in the exploratory subgroup analysis. The most common treatment-emergent adverse events with sacituzumab govitecan were fatigue, neutropenia, diarrhea, and nausea; all were more common with sacituzumab govitecan than with chemotherapy. No treatment-related deaths were reported in either treatment arm.