TROPiCS-02: Sacituzumab Govitecan in Relapsed/Refractory HR+/HER2- mBC
Expert Joyce O’Shaughnessy, MD, reviews data from the TROPiCS-02 study of sacituzumab govitecan in HR+/HER2- metastatic breast cancer.
Transcript:
Joyce A. O’Shaughnessy, MD: And I’m just going to run us through…a refresher on the [phase 3] TROPiCS-02 [trial; NCT03901339] data as well as DB-04 [the phase 3 DESTINY-Breast04 trial; NCT03734029]. Those 2 main options. And everyone is quite familiar, of course, with the antibody-drug conjugate sacituzumab targeting TROP-2, which is quite ubiquitous…it is conjugated to SN-38, the topoisomerase I inhibitor. And in TROPiCS-02, this was focused on HR [hormone receptor]-positive, HER2-negative patients. They had to have 2 to 4 prior lines of chemotherapy for metastatic disease. Very, very heavily pretreated. They had to have had a CDK4/6 inhibitor, and they were [randomly assigned] to full-dose sacituzumab, which is we know is 10 mg/kg, day 1 and day 8 on a 21-day cycle, versus single-agent chemotherapy with a primary end point of progression-free survival, but a key secondary end point of overall survival. And this, I will just point out at the bottom right, the median prior lines of chemotherapy was 3. In the metastatic setting, 95% of patients had visceral [metastases]. Almost 90% had liver [metastases], a super heavily pretreated patient population. Different than we’ll see in the DESTINY-Breast04 trial. And if we look at the top in the progression-free survival, the top left, and overall survival, top right, we see a statistically significant improvement in median PFS, which is somewhat modest. Just a 1.5 month improvement in median PFS, but it’s significant with a [hazard ratio] of 0.65, but the overall survival improved by 3.3 months. The median overall survival improved, and that was statistically significant. So you want to give your patient the best chance of survival in this later-line setting. We don’t use a single-agent chemotherapy here. We give the patient sacituzumab. Now, of course, there’s also the option of trastuzumab deruxtecan for some patients as well. We can see the response rate there, 14% with single-agent chemotherapy and 21% with sacituzumab. An analysis was done about whether there was a differential benefit of the sacituzumab in patients with high TROP-2 expression, with a H-score on the right versus lower on the left. And we see here, for example, down the bottom with regard to overall survival, we’re still seeing this 3-plus-month differential benefit on survival, regardless of high or low expression…. And then interestingly as well, the question of HER2 0 versus HER2-low status. There might be, for example, some patients who have a history of ILD [interstitial lung disease] with everolimus, and we don’t want to give the patient trastuzumab deruxtecan. But they’re HER2 low. So does sacituzumab work in those patients? And if we look at overall survival in the HER2-low patients in the bottom left, we see about a 4-month improvement in median overall survival. And then in the bottom right in the HER2 0 population, again, we see this differential benefit on survival. So regardless of HER2 status, HER low, HER2 0, we see the same differential benefit from sacituzumab compared to single-agent chemotherapy. And basically, with regard to time to deterioration and quality of life end points, it was favorable with regard to global health, quality of life, and fatigue.... The main toxicities we have to think about, and I want to hear from you, how you manage, what’s your experience with the sacituzumab? We have to watch out for grade 3, 4 neutropenia, diarrhea, 10% grade 3 or higher. Nausea is an issue as well, and alopecia and fatigue. So [it’s] mainly neutropenia and diarrhea [that] we have to be most conscious of with regard to sacituzumab.
Transcript is AI-generated and edited for clarity and readability.
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