By Karuna Jaggar, Former Executive Director and SABCS Guest Writer
In April 2020, the FDA approved a new type of immunotherapy, the antibody drug conjugate sacituzumab govitecan (brand name Trodelvy), a name so unpronounceable that even doctors at SABCS struggled and generally referred to it as SG. This is the first antibody drug conjugate for metastatic triple negative breast cancer shown to help people live longer, though it comes with severe side effects, and it’s the topic of my final blog post about immunotherapy news from the 2020 San Antonio Breast Cancer Symposium.
Part one of this four-part series can be found here, with links to each of the relevant pieces.
On Thursday, updated data from the 3 ASCENT trial was shared in a late breaking presentation by Dr. Hurvitz, reporting on the evaluation of a biomarker used to identify who is likely to benefit from sacituzumab govitecan among recurrent, pre-treated triple negative breast cancer (GS3-06).
Sacituzumab govitecan is the first TROP-2-targeted drug approved by the FDA and also the first antibody conjugate approved for metastatic triple negative breast cancer (TNBC) for use after other chemotherapies have been tried. Antibodies are proteins normally made by the immune system, and an antibody conjugate binds a targeted drug with chemotherapy, allowing selective delivery of chemotherapeutic agents to tumor cells. As context, in February 2013 the FDA approved the first antibody drug conjugate for HER2+ breast cancer, T-DM1 (Trustuzumab emtansine, which is sold by Genentech under the brand name Kadcyla). Where T-DM1 targets the HER2 receptor, SG targets Trop-2, a protein overexpressed in more than 90% of patients with triple negative breast cancer.
The FDA’s April approval was made under the FDA’s accelerated approval program using data from a single-arm phase 2 study, looking at the objective response rate, which measures the percent of patients whose disease decreased (partial response or PR) and/or disappears (complete response or CR). These surrogate endpoints don’t always correlate to overall survival so it was welcome news later this summer that the drug helps people with this hard to treat breast cancer live longer: median overall survival with the addition of SG was 12.1 months compared to 6.7 months without.
Data presented from 468 patients found that all patients with metastatic triple negative breast cancer who were treated with sacituzumab govitecan lived longer, regardless of subgroup. The researchers conducted exploratory biomarker assessment to evaluate the association between Trop-2 expression or germline BRCA1/2 mutation status. The majority (90%) of triple negative breast cancers have Trop-2 on cancer cells and around 10% of these cancers are associated with a germline BRCA mutation. While the researchers found that patients with moderate or high Trop 2 expression had the greatest benefit, all patients had some benefit. Unlike HER2-positive breast cancer, there doesn’t seem to be a threshold on the cell where it’s not effective. All patients benefited from SG, irrespective of BRCA mutation.
While Dr. Hurvitz concluded that “SG is generally well tolerated and has a safety profile consistent with previous reports,” the reality is that sacituzumab govitecan carries a black box warning, indicating a serious safety risk, for severe neutropenia (low white blood cells) and severe diarrhea. The most common side effects occurring in more than one in four people taking SG included nausea, neutropenia, diarrhea, fatigue, anemia, vomiting, hair loss, constipation, decreased appetite, rash and abdominal pain. The wholesale cost of treatment is estimated to be over $16,096 for a 21-day cycle.
With few other options, SG helps people with metastatic triple negative breast cancer whose cancer has stopped responding to other treatment live longer, albeit with serious side effects. Already there is interest in researching whether introducing this drug for early stage breast cancer may help prevent metastasis in the first place. As always, the cost and toxicity will need to be carefully weighed against the potential benefit.