AMEERA-1: Phase 1-2 Study of Amcenestrant, An Oral Selective Estrogen Receptor Degrader, With Palbociclib in Postmenopausal Women With ER+ HER2- Metastatic Breast Cancer - Episode 3
Dr Chandarlapaty elaborates on the challenges and unmet needs seen when treating ER+/HER2- metastatic breast cancer.
Sarat Chandarlapaty, MD: The challenges associated with systemic therapies is that first, we don’t know up front which is more likely to work longer. Second, the adverse effects associated with them. For the most part, these therapies work in the majority of patients, whether you choose to give endocrine therapy or chemotherapy. Most patients will derive some benefit and the cancer will eventually evolve and develop resistance. We don’t have a way of saying cancer A is most likely to benefit from CDK4 hormone combination, and cancer B is most likely to benefit from chemotherapy up front. That’s work that’s ongoing to develop biomarkers to separate those groups. In terms of chemotherapy, the other challenge is that it has more significant adverse effects associated with it, particularly myelosuppression, fatigue, and neuropathy. We have therefore largely relegated chemotherapies to later lines of therapy, mostly because of adverse effects because we can’t distinguish between chemotherapy and endocrine therapy for many patients in terms of antitumor effects.
The major problem we have is that patients do succumb to their disease in the advanced setting. We have patients who benefit for years on therapy, but their cancer evolves and develops resistance, and ultimately we can’t treat it anymore. We need agents in that setting. We need new therapies that can overcome those resistance mechanisms and even prevent the cancers from evolving. Second, as I said, most patients who develop advanced breast cancer present as a relapse of their primary breast cancer. If we had better therapies to prevent that relapse, then we could also improve our overall outcomes. Those are 2 major areas in which we need new therapies and better therapies.
Transcript edited for clarity.