An antibody-drug conjugate known as sacituzumab govitecan demonstrated significant clinical activity in heavily pretreated patients with relapsed/refractory metastatic triple-negative breast cancer (mTNBC), according to a new study.
“Metastatic TNBC is an aggressive disease with poor prognosis that tends to affect young women,” said Aditya Bardia, MBBS, MPH, of Massachusetts General Hospital Cancer Center in Boston. “Currently, there is no single standard chemotherapy available for relapsed/refractory mTNBC.”
Bardia presented results of a phase I/II trial of sacituzumab govitecan in this setting at the 2017 San Antonio Breast Cancer Symposium (SABCS), held December 5–9. The conjugate consists of SN-38, a compound derived from irinotecan, and a humanized monoclonal antibody targeting TROP-2, which is highly expressed in many epithelial cancers.
The single-arm, open-label study included 110 patients (109 women, 1 man) with mTNBC treated with 10 mg/kg of the agent on days 1 and 8 every 21 days, until progression or unacceptable toxicity. The patients, who had a median age of 55 years and had all received at least two prior lines of therapy for metastatic disease, received a median of 14.5 doses over a median of 4.9 months.
A total of 66 patients died, 30 remain in long-term follow-up, and 14 are still on the treatment. There was an objective response rate of 34%, with 3 complete responses and 34 partial responses. “The majority of patients had a reduction in the target lesion with this therapy,” Bardia said.
The median duration of response was 7.6 months according to local assessment, and 9.1 months by a central review. The median time to onset of response was 2 months, but Bardia noted that this ranged widely, with some patients responding only after several cycles of therapy. Nine long-term responders were progression-free for more than 1 year from the start of therapy.
There was no difference in response rates when stratified by age, prior regimens, or onset of metastatic disease. There were 19 patients who had received prior checkpoint inhibitor therapy, and 9 of them responded to sacituzumab govitecan (47%).
Neutropenia was among the most common adverse events (AEs), with grade 3/4 neutropenia reported in 41% of patients; however, only 7% had grade 3/4 febrile neutropenia. Bardia said AEs were managed well with supportive care, and with dose reductions (25% of patients).
“Sacituzumab govitecan as a single agent demonstrated significant clinical activity as a third line and beyond therapy in patients with relapsed/refractory mTNBC,” Bardia concluded. “Results demonstrate that sacituzumab govitecan has a predictable and manageable safety profile,” he added, and noted that other studies including in combination are now being considered. A phase III trial (ASCENT) is currently recruiting patients.