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Sacituzumab govitecan appears safe, effective in heavily pretreated breast cancer subtype
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Treatment with sacituzumab govitecan, a novel antibody-drug conjugate, resulted in objective responses among women with heavily pretreated hormone receptor-positive, HER-2-negative breast cancer, according to findings presented at the ASCO Annual Meeting.
The adverse events observed with sacituzumab govitecan (IMMU-132, Immunomedics) were tolerable and similar to those observed in earlier reports.
“Sacituzumab govitecan is a novel antibody-drug conjugate consisting of SN-38, the active metabolite of irinotecan, conjugated to a humanized monoclonal antibody targeting trophoblastic antigen-2, which is highly expressed in many epithelial cancers,” the researchers wrote. “A phase I/II basket trial investigated its activity in patients with advanced cancers. Results in HR-positive, HER-2-negative [patients with metastatic breast cancer] who had ≥1 prior hormonal therapy are presented here.”
Aditya Bardia, MD (MBBS), MPH, assistant professor of Medicine at Harvard Medical School, and colleagues enrolled 54 patients with estrogen receptor-positive, HER-2-negative breast cancer in this phase 1/2 basket trial. Eligible patients were aged 18 years and older, with measurable disease and an ECOG performance status of 0 to 1, and had received treatment with one or more prior therapies.
The median age of patients in this all-female cohort was 54 (range, 33-79). An ECOG performance status of 1 was reported in 56% of patients and almost all (98%) had received one or more prior lines of chemotherapy for metastatic disease. All patients (100%) had had received treatment with hormonal therapy for metastatic disease; 67% of patients had received 3 or more lines of hormonal therapy. Taxanes and anthracyclines in any setting were reported in 93% and 69% of patients, respectively.
Sacituzumab govitecan 10 mg/kg was administered on days 1 and 8 every 21 days until progression or unacceptable toxicity, with restaging scans every 8 weeks. The researchers assessed response to treatment according to RECIST 1.1 criteria and safety.
All patients received at least 1 dose of sacituzumab govitecan. The median number of doses provided was 11 (range, 1-74) and the median duration of treatment was 4 months (range, 0.2-26 months).
At the time of presentation, 23 patients had died; 1 patient was lost to follow-up at 5.3 months and 1 patient was missing, according to the study results. Of the 29 patients in long-term follow-up, 10 remained on treatment; 7 of those 10 patients achieved a partial response and the other 3 had stable disease.
Median duration of response to sacituzumab govitecan was 7.4 months (95% CI, 4.4-18.3 months). Median time to onset of response was 2.3 months (range, 1.5-7.8 months). Median PFS was 6.8 months (95% CI, 4.6-8.9 months).
The objective response rate, as determined by RECIST 1.1 criteria, was 31% (n = 17). Seventeen patients achieved a partial response; there were no complete responses. The clinical benefit rate of sacituzumab govitecan, as measured by complete responses plus partial responses plus stable disease for greater than or equal to 6 months, was 48% (n = 26).
None of the reported study deaths were attributed to sacituzumab govitecan. Adverse events were managed with additional medication or dosing changes; 28% of patients also received growth factor support.
“Sacituzumab govitecan as a single agent demonstrated significant clinical activity in heavily pre-treated [patients with HR-positive, HER-2-negative metastatic breast cancer],” the researchers wrote, with a “predictable and manageable safety profile.”
“Additional studies, including rational combinations, are currently being evaluated for metastatic breast cancer and other metastatic epithelial cancers.” – by Julia Ernst, MS
Reference:
Bardia A, et al. Abstract 1004. Presented at: ASCO Annual Meeting; June 1-5, 2018; Chicago.
Disclosure: Bardia reports serving in a consultant or advisory role for bioTheranostics, Genentech, Novartis, Pfizer and Spectrum Pharmaceuticals. Please see the study for all other authors’ relevant financial disclosures.
Perspective
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Sacituzumab govitecan is an interesting drug. It’s a monoclonal antibody directed against the Trop2 antigen, which is present in approximately 80% to 90% of breast cancers. The researchers presented data from 54 women with HR-positive, HER-2-negative breast cancer in this phase 1/2 basket trial. Median PFS was 6.8 months (95% CI, 4.6-8.9 months). This is substantially higher than what we would expect from historical controls, which is 4 to 5 months.
This was a phase 1/2 trial, so it’s preliminary data that will have to be confirmed in a larger trial, but a phase 3 trial of sacituzumab govitecan is already underway. That trial is looking at sacituzumab vs. investigator’s choice after second- or third-line therapy for triple-negative breast cancer. There will also likely be another larger trial in patients with HR-positive metastatic breast cancer.
I think people originally expected this agent to be limited to triple-negative breast cancer, but it probably won’t be. We’ll have to see – the trials need to be completed – but the bottom line is that sacituzumab may eventually be another option for ER-positive metastatic breast cancer, another tool for extending PFS besides chemotherapy, hormonal therapy and targeted therapy.
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