Sacituzumab Govitecan Benefit May Extend To HR-Positive, HER2-Negative Breast Cancer

Author: By Lynda Williams, Senior medwireNews Reporter 

medwireNews: Phase I/II trial findings indicate that the anti-Trop-2-SN-38 antibody–drug conjugate sacituzumab govitecan may have therapeutic potential for some patients with previously treated metastatic hormone receptor (HR)-positive, HER2-negative breast cancer. 

The IMMU-132-01 basket study results, published in the Annals of Oncology, indicate that a partial response was achieved by 31.5% of 54 women given sacituzumab govitecan 10 mg/kg on days 1 and 8 of a 21-day cycle and followed up for a median 11.5 months. The median duration of response was 8.7 months. 

When considering the further 33.3% of patients who achieved stable disease for at least 6 months, the clinical benefit rate was 44.4% in the cohort, report Kevin Kalinsky, from Columbia University in New York, USA, and co-authors. 

Further analysis revealed that the 32 patients who had previously received a CDK 4/6 inhibitor were less likely than the 22 patients who had not to achieve an objective response (25.0 vs 40.9%) or clinical benefit (37.5 vs 54.5%). 

Median progression-free survival was 5.5 months and overall survival 12.0 months in the full cohort; again patients who had previously received CDK 4/6 inhibitors had a poorer outcome than those who had not, with corresponding durations of 3.8 versus 7.6 months and 11.0 versus 21.7 months, respectively. 

The most common treatment-related adverse events at grade 3 or above were neutropenia (50.0%), anaemia (11.1%), reduced white blood cell count (9.3%) and diarrhoea (7.4%), followed by febrile neutropenia (3.7%), vomiting (3.7%), nausea (1.9%) and fatigue (1.9%). 

This safety profile is “consistent” with that previously reported from the IMMU-132-01 and TROPHY-U-01 trials of urothelial cancer and the ASCENT trial of metastatic triple-negative breast cancer, the investigators remark. 

Two patients discontinued sacituzumab govitecan because of adverse events but there were no treatment-related deaths or incidents of interstitial lung disease, severe neuropathy or grade 3–4 cardiac events. 

“This toxicity profile is unique among [antibody–drug conjugates], which may facilitate its combination with other therapies and make it an ideal backbone for therapeutic combinations in various disease settings”, comment Kevin Kalinsky et al.

Discussing the results, the investigators believe that, if confirmed, sacituzumab govitecan “could potentially provide a novel therapeutic option” for patients with pretreated HR-positive, HER2-negative metastatic breast cancer. 

They say that the phase III randomised open-label TROPiCS-02 trial will now further investigate sacituzumab govitecan with four chemotherapy regimens in patients who have progressed on between two to four chemotherapy regimens including a taxane, a hormonal therapy and/or a CDK4/6 inhibitor.  

Reference  

Kalinsky K, Diamond JR, Vahdat LT, et al. Sacituzumab govitecan in previously treated hormone receptor-positive/HER2-negative metastatic breast cancer: Final results from a phase 1/2, single-arm, basket trial. Ann Oncol; Advance online publication 14 September 2020. doi:10.1016/j.annonc.2020.09.004