I had the opportunity to present the patient reported outcomes from the ASCENT-03 study. The ASCENT-03 study is a study for patients with previously untreated metastatic triple-negative breast cancer who are not candidates for immune checkpoint inhibitors. So the primary efficacy results of this study have been presented at ESMO and published in The New England Journal of Medicine and at SABCS. The results I could present were the patient-reported outcomes based on the EORTC QLQ-C30 questionnaire.

What was the study design?

In ASCENT-03 patients were randomised 1:1 to either the experimental arm with sacituzumab govitecan on day 1 and day 8 of a three-weekly cycle, while patients in the control arm received chemotherapy according to the treating physician who could either choose between paclitaxel, nab-paclitaxel and carboplatin gemcitabine. In this PRO study we evaluated the EORTC QLQ-C30 questionnaires and the key secondary endpoints were change from baseline to week 25 in physical functioning and time to deterioration in fatigue. There were many exploratory endpoints like mean change from baseline in other domains, time to first deterioration and time to improvement in all other domains, including global health status.

What were the results?

The key secondary PRO endpoint of mean change from baseline to week 25 in physical functioning favoured SG. There was clearly a gradual worsening for physical functioning in the chemotherapy group while physical functioning scores were maintained in the SG group. For the other key secondary endpoint of time to deterioration in fatigue, this was similar between treatment groups.

When we focus on the key exploratory PRO endpoints, overall they were favouring SG. For example, there was a better time to deterioration in global health status, role functioning, fatigue, pain and dyspnoea and also insomnia – the time to improvement was faster for insomnia, physical role and social functioning. Besides this, there was a faster worsening of nausea or vomiting and also diarrhoea was observed with SG more compared than with chemotherapy.

What is the clinical significance of these results?

The clinical significance that we are talking about, the first-line treatment option here but for a disease for which we know that there is a high attrition rate between the first and the second line. So it’s important, and this study confirms that also from a quality of life perspective, having impact on the disease progression, such as SG has demonstrated in this setting, is often associated with improved PRO endpoints. This is also confirmed in this setting. So it’s not only from an efficacy point of view but also from a quality of life point of view that it seems to be the better option to preserve the patients’ overall wellbeing, to delay progression and this comes in this setting also with a delay in deterioration of quality of life.

Since this is a very important endpoint in patients with advanced breast cancer, to preserve quality of life as good as possible, this is very important in this setting to have also this confirmation that SG seems to be out-performing chemotherapy in first-line metastatic triple-negative breast cancer for patients ineligible for immune checkpoint inhibitors.