medwireNews: Early data suggest almost a third of patients with metastatic breast cancer could benefit from treatment with the Trop-2-directed antibody–drug conjugate sacituzumab govitecan.
Kevin Kalinsky (Columbia University Irving Medical Center-Herbert Irving Comprehensive Cancer Center, New York, USA) and co-investigators believe their findings are “encouraging in relation to current standard-of-care chemotherapies in this setting.”
The phase 1/2 trial included 54 women (median age 54 years) with hormone receptor-positive (HR+), human epidermal growth factor receptor 2-negative (HER2–) breast cancer who had received at least one line of endocrine therapy and at least one prior chemotherapy regimen for metastatic disease.
All of the women underwent treatment with intravenous sacituzumab govitecan 10 mg/kg on days 1 and 8 of a 21-day cycle until disease progression, unacceptable toxicity, death, or withdrawal of consent.
After a median 11.5 months of follow-up, the objective response rate (ORR) was 31.5%, all of which were partial responses. A further 13.0% of patients achieved stable disease for at least 6 months, giving a clinical benefit rate of 44.4%.
Kalinsky and co-authors report in the Annals of Oncology that the treatment responses were “durable,” with a median response duration of 8.7 months and a median progression-free survival (PFS) of 5.5 months. Median overall survival (OS) was 12.0 months.
Subgroup analyses revealed that the 32 individuals with prior CDK4/6 inhibitor exposure had an ORR of 25.0%. This compared with an ORR of 40.9% among the 22 individuals with no prior CDK 4/6 inhibitor use. The corresponding PFS in these two groups was 3.8 and 7.6 months, while OS was 11.0 and 21.7 months, respectively.
The researchers describe the safety profile of sacituzumab govitecan as “manageable” in this cohort. The most common grade 3 or worse treatment-related adverse event (AE) was neutropenia, occurring in half of the patients, followed by anemia (11.1%), leukopenia (9.3%), and diarrhea (7.4%).
There were 10 treatment-related serious AEs including two cases of febrile neutropenia and one case each of neutropenia, viral pneumonia, sepsis, diarrhea, nausea, vomiting, dehydration, and acute respiratory failure.
There were no treatment-related deaths, but two patients discontinued treatment due to AEs. There was also no reported cardiac toxicity, interstitial lung disease, or severe peripheral neuropathy.
Kalinsky et al remark that the “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.”
They also note that sacituzumab govitecan was granted accelerated FDA approval in 2020 for use in metastatic triple-negative breast cancer and is now being evaluated in a randomized phase 3 trial (TROPiCS-02) among heavily treated women with metastatic HR+/HER2- disease.
medwireNews is an independent medical news service provided by Springer Healthcare Ltd. © 2020 Springer Healthcare Ltd, part of the Springer Nature Group
Ann Oncol 2020; doi:10.1016/j.annonc.2020.09.004