Abeer Alenazi, Deputy Director, PGY2 Hematology/Oncology Pharmacy Residency Program at Prince Sultan Military Medical City, shared a post on LinkedIn:
“The FDA approval of gedatolisib plus fulvestrant, with or without palbociclib, may represent more than just a new treatment option for patients with HR-positive, HER2-negative metastatic breast cancer.
It also raises important questions about how we identify patients for PI3K pathway inhibition.
Until now, PI3K- and AKT-targeted therapies have largely been reserved for patients with PIK3CA, AKT1, or PTEN alterations, reflecting the biomarker-driven approach that has shaped precision oncology.
However, gedatolisib was approved for patients with PIK3CA wild-type disease after endocrine resistance, suggesting that dependence on the PI3K pathway may not always be explained by detectable genomic alterations alone.
This leads to an important question: Is genomic profiling sufficient to identify all patients who may benefit from PI3K pathway inhibition?
The approval highlights the possibility that tumor biology extends beyond the biomarkers we currently measure and that pathway activation may be driven by mechanisms not captured through routine genomic testing.
Whether future treatment guidelines will incorporate gedatolisib into standard sequencing remains to be seen. What is already clear, however, is that this approval has reignited an important scientific discussion about whether therapy selection should rely solely on genomic alterations or evolve toward a broader understanding of pathway activation.
Sometimes, the most practice-changing innovations do not simply introduce a new drug – they challenge the framework we use to decide who should receive it.”