Treatment selection following progression on endocrine therapy and CDK4/6 inhibitors remains an important clinical challenge in estrogen receptor-positive (ER+)/HER2-negative metastatic breast cancer. The emergence of ESR1 mutations can contribute to endocrine resistance, making molecular testing increasingly relevant to treatment decisions. A recent multicenter observational study conducted in Italy evaluated the effectiveness and tolerability of elacestrant in patients with ESR1-mutated disease who had previously received endocrine therapy and CDK4/6 inhibitors.
The study included 39 women treated across 13 oncology centers, with a median age of 67 years. All participants had documented ESR1 mutations identified through liquid biopsy and had experienced disease progression following prior treatment. Most patients had ESR1 mutations without concurrent PIK3CA alterations, while approximately 16% had both mutations. Investigators assessed objective response, disease control, survival outcomes, and treatment-related adverse events to better understand how elacestrant performs outside a controlled clinical trial setting.
Clinical findings showed an objective response rate of 28%, including one complete response and 10 partial responses. An additional 11 patients experienced stable disease, contributing to a reported disease control rate of 56%. Median progression-free survival was reported as approximately six months, while median overall survival had not been reached at the time of analysis. The researchers considered these outcomes generally consistent with previously published clinical trial and real-world evidence, although the relatively small study population limits broader conclusions.
The safety analysis also provided insight into treatment tolerability in routine oncology practice. Fatigue and gastrointestinal symptoms were among the reported adverse events, with most toxicities classified as mild or moderate. Approximately 64% of patients had no reported treatment-related toxicity, while 15% required dose reductions and 4% permanently discontinued treatment because of adverse events. These observations contribute to the growing body of real-world safety information available to clinicians evaluating endocrine-based treatment approaches.
Overall, the findings provide additional evidence regarding elacestrant use in patients with ESR1-mutated metastatic breast cancer following prior endocrine therapy and CDK4/6 inhibition. The investigators emphasized the importance of ESR1 mutation testing in identifying patients who may be candidates for targeted endocrine treatment. They also acknowledged that early progression remains a challenge for some patients and that additional research is needed to better understand resistance mechanisms and identify clinical characteristics associated with treatment outcomes.
Source: Greco M, et al. A Real-World Study on the Effectiveness and Safety of Elacestrant in Patients with ESR1-Mutated Metastatic Breast Cancer Progressing After CDK4/6 Inhibitors and Endocrine Therapy. PMID: 42449589. PubMed Central.