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Joyce O’Shaughnessy, MD:
Reflecting on SABCS, I am looking forward to having a new oral SERD. We have not heretofore had anything proven effective for patients with ESR1 mutations, which are very common—45% of the EMERALD population. These mutations predict for varying degrees of ET resistance. I look forward to using elacestrant once we have it available for patients with an ESR1 mutation who are likely to be at least somewhat ET sensitive.
I was also pleased to see the KEYNOTE‑522 data. The EFS improvement in all the subgroups in the curative setting gives me confidence to tell my patients with stage II, node-negative disease that they too, will have improved outcome with ne/adjuvant pembrolizumab. The problem is we cannot predict who will recur, and so we have to give those patients every benefit of the doubt in using preoperative pembrolizumab.
I also applaud the substantial survival advantage that ribociclib showed in the first‑line setting—regardless of the subset of patients, even in the patients with the most difficult-to-treat disease. I also do not want to forget the impressive results for Dato‑DXd overall, T-DXd efficacy against brain metastases, and the impressive survival data with tucatinib for patients with CNS metastases.
Sara Tolaney, MD, MPH:
I agree with you, and I think that much of these data indicate that we are making tremendous headway in improving outcomes for our patients. I am excited about all these new agents that can help our patients.
As you point out, an oral SERD is a tremendous advantage. To have something so convenient for patients, to be able to avoid intramuscular injections and show advantage compared with fulvestrant are all important. I think it is going to shift the field because it is nice to have a new endocrine agent for metastatic disease, one that may even help patients with early‑stage disease in the future.
I think the wave of ADCs is changing our field. Dato‑DXd is one example. But we already have sacituzumab govitecan, T‑DM1, and T‑DXd, and now I think the focus will be on refining how we use and sequence ADCs, and whether they will move into early-stage disease, even a perioperative setting or perhaps adjuvant therapy for TNBC. I think we have a lot of room to figure out how to optimize the use of ADCs.
Finally, I think immunotherapy is here to stay. It took the breast cancer community some time to figure out how to use immunotherapy, but it is remarkable to see the benefits in combination with chemotherapy, the survival advantage in the metastatic setting, and the EFS benefit in the early‑stage setting.