TROPiCS-02, as you know, is a randomised multi-centre open label phase III trial that evaluated the antibody drug conjugate sacituzumab govitecan versus a menu of chemotherapy agents of physician’s choice in patients who had hormone receptor positive, HER2 negative metastatic breast cancer who were heavily pre-treated. The eligibility included at least one line of endocrine therapy in the metastatic setting, as well as two to four lines of chemotherapy given for metastatic disease and, in addition, all patients had to have received a CDK4/6 inhibitor and a taxane in any setting. The randomisation was one-to-one and patients were stratified based on a number of factors including visceral metastases, endocrine therapy for more than six months in the metastatic setting, and then the chemotherapy. The primary endpoint was progression free survival, but based on blinded independent central review, and the secondary end points included overall survival, quality of life, safety, response, duration of response, the usual suspects.
What we found in this trial were 95% of the patients had visceral metastases and the median number of lines of prior chemotherapy was three, with the range in the sacituzumab treated patients of zero to eight lines of chemotherapy in the metastatic setting. Many patients had been on long courses of prior endocrine therapy as well as CDK4/6 inhibitor therapy, with that long median time from initial diagnosis of metastatic disease of four years that sacituzumab resulted in a statistically significant improvement in progression free survival by central review. The median progression free survival was 5.5 months for sacituzumab and four months for chemotherapy, with a hazard ration of 0.66, representing a 34% relative improvement, and a p-value of 0.0003.
We looked at landmark analyses because a subset of these patients who had heavily pre-treated disease progressed rapidly in the first two months after starting treatment. At one year, 21% of patients were free from progression or death, treated with sacituzumab versus 7% of patients treated with chemotherapy, representing a three-fold difference in this landmark analysis at twelve months.
Safety is important, and in this trial there were no new safety signals, and overall safety was manageable, with the most common toxicities similar to prior studies, including neutropenia and diarrhoea. There were six deaths in patients treated with sacituzumab versus zero with chemotherapy. But only one death, a neutropenic colitis, was associated by the investigator with treatment with sacituzumab. The rest of the deaths were not related to study therapy by investigator assessment, and didn’t represent any clear pattern, for example COVID, pneumonia, and other causes.
We looked at quality of life, and overall the global quality of life scale showed improvement in patients treated with sacituzumab versus chemotherapy, as did fatigue, and the pain scales were similar. The overall response was improved, as well as the clinical benefit, rate and the duration of response in patients who were treated with sacituzumab versus chemotherapy.
So, in summary, we did show in this heavily pre-treated patient population that sacituzumab improved progression free survival, and had a manageable safety profile. In this uniformly heavily pre-treated patient population is important because now sacituzumab can offer a new treatment option in our sequential treatment options for these patients.