What’s Next in Breast Cancer Treatment After Endocrine Therapy Progression?
Erika Hamilton, MD, discusses how to approach treatment after progression on first-line therapy and hormone receptor-positive breast cancer.
Erika Hamilton, MD, director of Breast Cancer Research at the Sarah Cannon Research Institute, discusses how important it is to continue targeting ER after progression on endocrine therapy in patients with breast cancer.
She then highlights the available treatment options for patients who progress on CDK4/6 inhibitors and the next steps for research in this space.
Transcription:
0:09 | It is really important. There are many patients whose tumors continue to be sensitive to endocrine agents. One of the biggest unmet clinical needs right now is that we do not have a reliable way to predict which patients fall into this category. Some patients post-CDK4/6 may not benefit from further endocrine therapies, even though their tumors are still ER-positive. They may or may not have an ESR1 mutation, but we lack a strong assay to determine whose tumor remains endocrine-sensitive and whose does not.
0:40 | [From my experience] working with all these classes of agents through clinical trials at Sarah Cannon, I have seen patients stay on these novel agents for up to 2 years. It is hard to argue against trying additional endocrine therapies, with close follow-up, because some patients achieve meaningful disease control for a significant amount of time without having to move on to more toxic treatments like chemotherapy.
1:12 | Through clinical trials, we have explored many of these new agents, often based on specific mutations. For ESR1 mutations, we use lasofoxifene [Fablyn]; for PIK3CA or PTEN mutations, we consider alpelisib, or capivasertib [Truqap] in combination with fulvestrant. We still have PARP inhibitors for those with BRCA alterations, and while fulvestrant as a single agent is available, it is not very exciting in terms of activity. So, we typically use fulvestrant in combination therapies, either with everolimus or perhaps abemaciclib, based on the recent post-MONARCH data.
1:48 | For patients we suspect are endocrine-resistant—such as those who progressed on their CDK4/6 inhibitor within 6 months, when the average progression-free survival should have been closer to 24 months—this indicates that the cancer may no longer be responding to estrogen axis modulation. In these cases, we are likely moving on to antibody-drug conjugates [ADCs], which are new and have shown promise. We now have 2 ADCs approved for ER-positive breast cancer: fam-trastuzumab deruxtecan-nxki [Enhertu; T-DXd], a HER2-targeting [antibody-drug conjugate (ADC)] for those with low HER2 expression, and sacituzumab govitecan [Trodelvy], a TROP2-targeting ADC. It is definitely a rapidly evolving field.
2:26 | One of the takeaways is that genomic profiling patients' tumors are here. It used to be something we talked about being actionable in the future, and now, with ESR1, PI3K, BRCA, PTEN, this is actionable, and so we do need to think about after CDK4/6 getting this mutation data, whether this is from either tissue or a blood-based assay, and thinking about which of the options our patient in front of us may qualify for.
