Understanding the Side Effects of RLY-2608 in HR+, HER2– Breast Cancer

Investigators evaluated the updated efficacy of treatment with RLY-2608, a mutant-selective PI3Kα inhibitor, when combined with Faslodex (fulvestrant) for patients with PIK3CA-mutant hormone receptor (HR)-positive, HER2-negative advanced breast cancer during the ReDiscover trial, according to Dr. Sarah Sammons.

It was during this study that investigators found that the investigative agent demonstrated a favorable safety and tolerability for patients within this population, as well as an acceptable progression-free survival rate across PIK3CA genotypes in patients with advanced PIK3CA-mutant disease, supporting the advancement of pivotal testing for this combination, which is planned for later this year, according to the study abstract.

Additionally, treatment-related side effects which were listed included hyperglycemia, nausea and fatigue, all of which were noted to be generally low-grade, manageable and reversible.

To further discuss this topic, Sammons sat down for an interview with CURE live on site at the 2025 ASCO Annual Meeting where she discussed how RLY-2608 differs from existing PI3K inhibitors in terms of side effects, and what this might this mean for patients who have struggled with tolerability in the past.

Sammons is a senior physician at Dana-Farber Cancer Institute, in Boston, Massachusetts, where she is also the associate director of the Metastatic Breast Cancer Program. She also serves as the assistant professor of Medicine at Harvard Medical School.

Transcript:

I think it's differentiated in terms of side effects. We're still seeing some hyperglycemia, but it's generally low grade. What's very nice about it, compared to other drugs in its class, is that I'm seeing less diarrhea in my patients, very little rash and very few oral mouth sores, which can be really distressing for patients.

Of course, there are still some low-grade side effects — the "Holy Grail" would be none — but they seem to be manageable and compare favorably to other drugs in the class.

Transcript has been edited for clarity and conciseness.

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