We had the opportunity to present the ASCENT-03 study which was a randomised phase III study with SG or physician’s choice, which is chemotherapy, either paclitaxel, nab-paclitaxel or CarboGem, in patients who are not candidates to receive immune checkpoint inhibitors and who have first-line triple-negative breast cancer, metastatic setting. So basically, as we all know, the majority of patients with metastatic triple-negative breast cancer are not adequate to receive immune checkpoint inhibitors. The majority of them because the tumours do not express PD-L1 so we know that we require this at 10 or higher CPS score to receive immune checkpoint inhibitors; if not, it is not working, and also maybe because of some comorbidities. It is true that for those patients who receive immune checkpoint inhibitors in the early breast cancer setting we do not know if it will work or not.

So for these patients chemotherapy is the standard of care and this provides a median PFS in the range of 4-6 months maximum, so very poor outcomes. What do we do afterwards? We have different drugs, however, the most important drug in terms of the benefit shown is the anti-TROP2 antibody-drug conjugate sacituzumab govitecan. It has shown to improve not only PFS and overall response rate but also overall survival in, again, pre-treated patients with triple-negative breast cancer but also pre-treated patients with ER+ HER2- disease. So unfortunately about 50% of patients will be unable to receive subsequent lines of therapy because of death or because the quality of life is not good enough to continue with chemotherapy-based strategies.

So, based on all this data, we wanted to explore if SG was superior to chemotherapy for those patients who did not qualify for immune checkpoint inhibitors in first-line triple-negative breast cancer. So the primary endpoint of this study was progression free survival by BICR and patients were stratified based on their region and also based on their disease status.

Roughly the median progression free survival, the primary endpoint of the study, was met; the hazard ratio in favour of SG was 0.62. The median PFS with chemotherapy was 6.9 months; with SG it was 9.7 months, an absolute improvement of 7.2 months. I think it’s very important to remark that in this study those patients who were randomised to the control arm and experienced progression of disease by BICR were allowed, and it was provided by the sponsor, to receive SG in second line. Why? Because SG has been approved in many countries and it has demonstrated to improve survival, but not in all countries approved. So we gave the opportunity for those patients to receive SG.

Of course, this could have an impact on survival; let’s see with more mature data. Because at this time overall survival was only descriptive, it was immature. Nevertheless, the hazard ratio was 0.98 and it’s important to remark that for those patients who received second-line therapy 82% of them received SG in the control arm.

Of interest, progression free survival 2, PFS2, was much higher with SG compared with chemotherapy: with chemotherapy median 14 months, with SG 18.2 months, an absolute improvement of 4.2 months. Let’s see with more follow-up if we can observe also an improvement in overall survival.

Safety. I think that the good news is that the safety profile of SG is very well known, nothing was unexpected. Diarrhoea was observed in the range of 50% of patients more or less but grade 3 or higher in the range of 9%. 72% of patients developed neutropenia, 43% grade 3 or higher. Unfortunately six patients did have treatment-related deaths, all of them because of infections and in five of them we had neutropenia. These five patients qualified to be considered high risk for febrile neutropenia and none of these patients received the recommendation of prophylactic treatment with GCSF. So that’s something that we have to emphasise, the importance of giving GCSF prophylactically to these patients.

So, taking into account all these aspects, we can consider that SG is one of the best options to treat our patients in the first-line setting with metastatic triple-negative breast cancer if they do not qualify for immune checkpoint inhibitors.

I would like to compliment something here Sara Tolaney presented at ASCO 2025, the results of the ASCENT-04 study. It’s interesting to highlight that in patients who qualified for immune checkpoint inhibitors, also SG plus pembrolizumab was superior to chemotherapy and pembrolizumab.