Therapeutic Sequencing for ESR1m, ER+, HER2- MBC: Efficacy and Safety Considerations
Panelists highlight that oral endocrine therapies for hormone receptor-positive breast cancer are generally well tolerated with manageable mild adverse effects, whereas PI3K/AKT/mTOR inhibitors often cause more challenging toxicities such as hyperglycemia and diarrhea, leading many clinicians to prioritize better-tolerated endocrine agents initially to balance efficacy with patient quality of life.
Toxicity profiles play a critical role in selecting treatments, especially when balancing efficacy with patients’ quality of life. One oral agent used in hormone receptor-positive breast cancer is generally well tolerated, with the most common side adverse effects involving mild gastrointestinal symptoms, such as nausea. These symptoms are usually manageable with simple supportive care like such as oral antiemetics and rarely lead to treatment discontinuation. Fatigue is also reported but can be difficult to attribute solely to the drug, as underlying disease often contributes. Patients often prefer this therapy due to its oral administration, which allows greater flexibility and convenience compared to with injectable endocrine therapies.
In contrast, targeted therapies that inhibit the PI3K/AKT/mTOR pathway tend to have a more challenging toxicity profile. A major concern with these agents is hyperglycemia, which can occur in approximately 30% to 40% percent of patients. Because this side adverse effect develops rapidly, typically within the first two 2 weeks of treatment, intensive glucose monitoring is necessary early on. Monitoring protocols often include blood sugar checks within days of starting therapy and weekly measurements for the first one 1 to two 2 months. If hyperglycemia is detected, more frequent monitoring and intervention with antihyperglycemic medications may be required. This increases the clinical management burden and can impact patient quality of life.
Additionally, diarrhea is a frequent issue with these pathway inhibitors and can further complicate treatment tolerability. Due to these potential toxicities, the decision to use such agents often weighs the expected benefit against the added side adverse effect burden. Many clinicians may prefer to start with the better-tolerated oral endocrine therapy and reserve combination targeted treatments for later lines, especially when considering patient comorbidities and preferences. Overall, the goal remains to maximize efficacy while minimizing adverse effects to maintain patient well-being throughout treatment.
