Matthew Kurian, Assistant Professor of Medicine at the University of Kentucky College of Medicine and Physician at St. Elizabeth Healthcare, shared a post on LinkedIn:
“BREAKING: FDA Approves Gedatolisib with Fulvestrant (± Palbociclib) for HR+/HER2− Metastatic Breast Cancer
The FDA has approved gedatolisib combination with fulvestrant ± palbociclib for patients with HR-positive, HER2-negative, PIK3CA wild-type locally advanced or metastatic breast cancer following progression on endocrine therapy.
While this is a major milestone for patients, it also creates one of the most interesting treatment questions we’ve faced in years: How will we now navigate the expanding PI3K/AKT/mTOR landscape?
CAPItello-291 (capivasertib + fulvestrant):
- Population: PIK3CA, AKT1, or PTEN-altered tumors after progression on endocrine therapy.
- Median PFS:7.3 vs 3.1 months (HR 0.50).
- Oral therapy (4 days on/3 days off).
- Key grade ≥3 toxicities: rash (~12%), diarrhea (~9%), hyperglycemia (~2%).
INAVO120 (inavolisib + palbociclib + fulvestrant):
- PIK3CA PIK3CA-mutated disease recurring during or within 12 months of adjuvant endocrine therapy or endocrine-resistant metastatic disease.
- Median PFS: 15.0 vs 7.3 months (HR 0.43).
- An all-oral targeted option (plus monthly fulvestrant).
- Personally, I don’t encounter many patients relapsing within 12 months of adjuvant endocrine therapy with CDK4/6 available, so I’m curious how often others are using this regimen.
VIKTORIA-1 (gedatolisib + fulvestrant ± palbociclib):
- Population: PIK3CA wild-type disease after progression on CDK4/6 inhibitor + aromatase inhibitor.
- Triplet arm: Median PFS 9.3 vs 2.0 months (HR 0.24; 76% reduction in risk of progression or death).
- Doublet arm: Median PFS 7.4 vs 2.0 months (HR 0.33).
- Weekly IV therapy (3 weeks on, 1 week off) plus monthly fulvestrant.
One practical consideration that isn’t discussed enough is access. Practicing in Kentucky, many of my patients travel 2–3 hours for treatment. A weekly infusion schedule can be a significant burden. On the other hand, some patients prefer IV therapy because they appreciate the routine monitoring and regular interaction with their care team. Highly impressive in PIK3CA wild type. Some question regarding if fulvestrant alone is a fair comparison or not, but overall great data and I think a compelling option.
As our options continue to grow, choosing therapy will be about much more than efficacy – it will require balancing biology, biomarkers, toxicity, logistics, and patient preferences.
How are you planning to use capivasertib, inavolisib, and now gedatolisib in your practice?”
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