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:
“CAPItello-291 Final OS Update at ESMO Breast 2026
At first glance, some may see this as a ‘negative’ OS study. But that’s an oversimplification.
In the PIK3CA/AKT1/PTEN-altered population:
- Capivasertib + fulvestrant
- Placebo + fulvestrant
Median OS: 28.5 vs 30.4 months
HR 0.83
p = 0.201
But:
- This was a secondary endpoint
- The trial was never powered for OS
And in HR+/HER2− metastatic breast cancer, proving OS benefit is incredibly difficult because:
- Patients often live years after progression
- Multiple subsequent therapies dilute OS effects
- Post-progression treatment imbalance matters
In fact, CAPItello-291 showed more subsequent targeted/CDK4/6 therapy use in the control arm after progression. So a ‘non-significant OS’ result here does not equate to a proof that no OS benefit exists.
Importantly:
- Strong biomarker-driven PFS benefit (~50% risk reduction)
- Delayed subsequent therapy/PFS2 benefit (In the PIK3CA/AKT1/PTEN-altered population, median PFS2 was 15.9 months with capivasertib plus fulvestrant versus 11.1 months with placebo plus fulvestrant, with a hazard ratio of 0.68)
- Maintained quality of life
- No OS detriment signal
And let’s not forget the phase II FAKTION trial:
- OS: 39.0 vs 20.0 months
- HR 0.46
- p = 0.005
That provides real biologic plausibility that AKT pathway inhibition matters long term.
In modern HR+ metastatic breast cancer, OS is becoming an increasingly blunt endpoint for targeted therapies given crossover, sequencing, and long post-progression survival. The OS headline may not have crossed the statistical line, but biologically and clinically, capivasertib remains a very relevant option in my opinion.”
