Unmet Needs in PIK3CA-Mutated HR+/HER2-Negative Advanced Breast Cancer

Dr. Jason Mouabbi discusses remaining unmet needs and practical considerations in the management of PIK3CA-mutated HR-positive/HER2-negative advanced breast cancer. He highlights unanswered questions regarding the role of subsequent PI3K pathway inhibition after progression on first-line inavolisib-based treatment, as well as the appropriate treatment approach for patients with well-controlled diabetes who may not have met the eligibility criteria of clinical trials. He also discusses the lack of clinical trial data supporting substitution of ribociclib for palbociclib within the inavolisib-based regimen and emphasizes the need for safety data before making such changes in routine practice. Looking ahead, Dr. Mouabbi describes interest in mutant-selective PI3K inhibitors that may potentially limit treatment-related toxicities. For community oncologists, he emphasizes the importance of molecular testing at metastatic diagnosis and subsequent progression, baseline HbA1c assessment, home glucose monitoring, and proactive management of hyperglycemia. He also underscores collaboration with primary care and endocrinology for diabetes management and timely treatment modification when clinically significant hyperglycemia develops.