The FDA recently granted approval to sacituzumab govitecan-hziy (Trodelvy™, Immunomedics, Inc) for patients with metastatic triple-negative breast cancer (TNBC) who have received at least two prior therapies. Approval was based on a clinical trial (NCT01631552) that enrolled 108 patients with metastatic TNBC. In an interview with i3 Health, Sara Tolaney, MD, MPH, one of the study authors, provides insights on treating TNBC and the significance of the sacituzumab govitecan approval.
What are the most challenging aspects of treating patients with refractory metastatic TNBC?
Sara Tolaney, MD, MPH: I think to date, TNBC has been challenging for us because many patients with triple-negative disease will recur soon after presentation of their primary breast cancer and in general, survival for patients with TNBC has been limited, with the median survival being somewhere around 13 to 18 months. We have seen some improvement since the introduction of immunotherapy for triple-negative disease where the median overall survival for programmed death-ligand 1 (PD-L1)-positive triple-negative disease is probably up to 25 months. The challenge has been that patients generally have had treatment options that have predominantly been limited to chemotherapy and that their median duration of time on chemotherapy is quite limited because usually they often develop resistance very quickly to treatment.
Can you comment on the significance of the approval of sacituzumab govitecan for refractory metastatic TNBC?
Dr. Tolaney: We are all very excited about the FDA approval of sacituzumab govitecan because this agent is a unique antibody drug conjugate that has demonstrated very impressive activity in patients with refractory metastatic TNBC. In a previous basket study that had 108 patients, the agent was associated with a 33% objective response rate and median progression-free survival of about 5.5 months. This is far superior to what we generally would see with standard chemotherapy in a patient receiving third-line or beyond chemotherapy for metastatic TNBC. This agent offers a very efficacious treatment option for patients with refractory metastatic triple-negative disease.
How do you see the treatment landscape evolving in the coming years for patients with TNBC?
Dr. Tolaney: Currently our standard of care has been to use chemotherapy with immunotherapy in PD-L1 positive tumors in the first line setting for metastatic TNBC, and then predominantly use chemotherapy with subsequent lines of therapy. For patients with germline BRCA mutations, we will offer a PARP inhibitor at some point in the course of their metastatic disease.Now we will have the opportunity to use sacituzumab govitecan in the third line and beyond for our patients, which represents an important treatment option.
I think we will see treatment for triple-negative disease evolve. There are lots of promising new agents and strategies for combining these new agents. We wonder if we will be able to make immunotherapy work beyond just patients who have PD-L1–positive triple-negative tumors. There is work ongoing looking to see if adding AKT inhibition to immunotherapy and chemotherapy will allow not only better activity of the combination but also potentially allow benefit of immunotherapy even amongst PD-L1–negative tumors. I think we will need to better learn how to address patients who become refractory to immunotherapy and whether or not there would be any further benefit to expose these patients to immunotherapy in the future. We're also going to be thinking about novel combinations again for these new agents. For sacituzumab govitecan, many of us are interested to know how it would combine with immunotherapy and if it will be effective in an even earlier line of therapy. There is a trial that will be starting soon through the German Breast Group (GBG) looking at sacituzumab govitecan in patients with residual disease after preoperative therapy. I'm hopeful that many of these novel agents will potentially move into the early disease setting.
Do you have any advice for community oncologists to treat this patient population?
Dr. Tolaney: I think for patients who have metastatic triple-negative disease, it's certainly very important to test patients for PD-L1 and to offer immunotherapy for those patients who have PD-L1–positive disease and to also consider clinical trial options for these patients because there are lots of new agents in development that may offer a nice opportunity for them.
About Dr. Tolaney
Sara Tolaney, MD, MPH is a medical oncologist at Dana-Farber Cancer Institute and Brigham and Women's Hospital. She is also a clinical investigator at the Breast Oncology Center. Her research focuses on the development of novel therapies in the treatment of breast cancer.
For More Information
Clinicaltrials.gov (2020). Phase I/II study of IMMU-132 in patients with epithelial cancers. NLM Identifier: NCT01631552
Trodelvy™ (sacituzumab govitecan-hziy) prescribing information (2020). Immunomedics, Inc. Available at: https://www.accessdata.fda.gov/drugsatfda_docs/label/2020/761115s000lbl.pdf
Image Courtesy of Dana-Farber Cancer Institute
Transcript edited for clarity. Any views expressed above are the speaker's own and do not necessarily reflect those of i3 Health.