Dr Moore provides a detailed summary of the scope and findings from the TROPiCS-02 study.
Heather Moore, CPP, PharmD: The objective of the [phase 3] TROPiCS-02 study [NCT03901339] was looking at the efficacy and safety of sacituzumab and hormone receptor-positive, HER2-negative [HR+/HER2-] metastatic breast cancer patients who were endocrine resistant or refractory. We already had an approval for sacituzumab in the triple-negative setting, but this was looking at it in a new patient population. Just taking a step back, sacituzumab is an antibody-drug conjugate which is targeting Trop2 [transmembrane glycoprotein encoded by Tacstd2 gene] that is linked with SN-38, which is our chemotherapy and the active metabolite of irinotecan. There was a previous interim analysis that was presented with an overall survival benefit, but this is the final analysis that was presented at [the American Society of Clinical Oncology meeting].
This was an exploratory analysis of overall survival. They did use longer median follow-up with the final, and they used a total of roughly 13 months.
Patients included in the TROPiCS-02 study were HR+/HER2- metastatic breast cancer patients. They had to have received a prior taxane endocrine therapy that also included a CDK4/6 inhibitor and 2 to 4 lines of prior chemotherapy. Patients were randomized 1:1 to receive sacituzumab. This was at standard dosing, so 10 mg/kg on days 1 and day 8 of a 21-day cycle. This was compared [with] physician’s choice of chemotherapy. The primary end point of this study was looking at progression-free survival, and this was initially blinded by an independent central review board, so this was the interim analysis previously. Secondary end points looked at overall survival and safety. The exploratory end point was overall survival, but actually looking at patients with HER2 immunohistochemistry, or IHC, more so looking at the HER2-low status.
The TROPiCS-02 study included 543 patients. Patients had received on median 3 prior lines of therapy, looking at progression-free survival, which was the primary analysis. We saw 5.5 months of sacituzumab, compared [with] 4 months with chemotherapy. This also translated into the overall survival with on median, 12.5 months. Looking at overall survival rates, 60.9% of patients were still alive at 12 months with sacituzumab compared [with] 47.1% of patients who were receiving chemotherapy. When looking at 24 months, 25.6% of patients on sacituzumab compared [with] 21.1% of patients who were receiving otherwise physician’s choice of chemotherapy. Overall survival rates, 14.4 months with sacituzumab vs 11.2 months [on chemotherapy]. This was statistically significant and shown to be roughly a 3.2-month median overall survival improvement. When we break this down by the exploratory end point, which was looking at the HER2 IHC status, we saw that patients who had an IHC of zero on median was 13.6 months with sacituzumab compared with 10.8 months for patients who were receiving chemotherapy. Now for patients who were HER2-low, meaning they were 1-plus or 2-plus, the median was 15.4 months with sacituzumab compared [with] 1.5 months with physician’s choice.
From a safety perspective, grade 3 or higher adverse events took place in roughly 74% of patients. Six percent led to a treatment discontinuation; 66% of these resulted in a treatment delay, and 34% in a dose reduction. When thinking about adverse events, over half of patients, 52%, experienced either grade 3 or grade 4 neutropenia. Seven percent of patients experienced anemia that was considered grade 3 or grade 4. Thinking about [nonhematological] adverse effects, all grade diarrhea was seen in roughly 62% of patients; 59% of patients experienced nausea, and 24% of patients experienced vomiting. I do want to mention that there was one fatal event secondary to sacituzumab, and that was septic shock caused by neutropenic colitis.
TROPiCS-02 showed us that sacituzumab is a good option for HR+/HER2- metastatic breast cancer after patients have received at least 2 lines of prior chemotherapy and endocrine therapy. What was helpful to see with the study is that the survival benefit was consistent across Trop2 expression regardless of subgroup. What we saw is that regardless of how much they expressed Trop2 is that the benefit was still seen. The safety profile is pretty consistent with what we’ve seen with other studies. Thinking about the [phase 3] ASCENT study [NCT02574455] and the [phase 1/2] IMMU-132 study [NCT01631552], there weren’t any new safety signals, but we do still need to be mindful thinking about adverse effect profiles and how we manage our patients and the setting of neutropenia, nausea, diarrhea.
What we know from the TROPiCS-02 study is that sacituzumab is a good option for HR+/HER2- metastatic breast cancer patients. But what the real question is, is where do we sequence this? Based off of TROPiCS-02, we know that patients do require 2 prior lines of therapy, but we’re generally going to give trastuzumab deruxtecan, or T-DXd, after 1 prior line of chemotherapy for patients who are HER2-low based off of the efficacy rates that we’ve seen with that. Another thing to be mindful of is that when we’re thinking about mechanism is that T-DXd is also linked with a topoisomerase inhibitor, as is sacituzumab. Sometimes there can be concern for resistance when we’re giving sacituzumab after trastuzumab deruxtecan. Another thing we have to be mindful of more from an adverse effect standpoint is that when we’re thinking about how we’re managing these patients, we do tend to see quite a bit of neutropenia. Very often we’ll have patients who are in a combination of long-acting or even sometimes with short-acting growth factor just in an effort to maintain their treatment. The black box warning is very real. It’s something that we deal with on a daily basis with anecdotally half of our patients being on growth factor.
Transcript is AI-generated and edited for clarity and readability.