Matthew Kurian, Physician at St. Elizabeth Healthcare, shared on LinkedIn:
“Another major development in HR+/HER2− metastatic breast cancer!
The FDA has accepted the sNDA for gedatolisib in PIK3CA-mutated disease on November 9th, with a decision expected June 25, 2027.
The phase III VIKTORIA-1 trial demonstrated impressive results following CDK4/6 inhibitor progression:
PIK3CA-mutated cohort:
- Gedatolisib + fulvestrant + palbociclib: PFS 11.1 vs 5.6 months with alpelisib + fulvestrant (HR 0.50)
- Gedatolisib + fulvestrant: PFS 11.3 vs 5.6 months (HR 0.51; descriptive analysis)
- Grade ≥3 hyperglycemia: 0–2.6% with gedatolisib regimens vs 14.5% with alpelisib
Gedatolisib inhibits all class I PI3K isoforms and mTORC1/2, offering broader pathway inhibition than PI3Kα-selective agents.
Interestingly, adding palbociclib did not appear to provide meaningful additional PFS benefit, while substantially increasing grade ≥3 neutropenia (58.8% vs 0%)
My take
Already FDA-approved in PIK3CA wild-type disease, gedatolisib may soon become an option regardless of mutation status. I’m finding that more and more of my own patients are reaching this post-CDK4/6 treatment setting without targetable mutations, making this an increasingly relevant option.
I am finding some significant logistical barriers in my institution and others around the country I speak with to use the drug despite commercial use being available. Something that will need to be fixed in order for this to be successful strategy. We can’t wait on J-codes to treat patients that need access.
An important sequencing question remains:
How effective will oral SERDs and other PI3K/AKT/mTOR-targeted therapies be after progression on gedatolisib? As this is how I think the drug may actually be used in real world populations.”
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