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Adding the AKT inhibitor capivasertib to fulvestrant doubled progression-free time, especially in tumours with PI3K-pathway mutations.
CAPItello-291, trial NCT04305496 sponsored by AstraZeneca and reported in 2022, showed that adding the AKT inhibitor capivasertib to fulvestrant doubled progression-free time in HR-positive, HER2-negative advanced breast cancer after an aromatase inhibitor, with the largest effect in tumours carrying PIK3CA, AKT1 or PTEN alterations. It randomised 708 women, about seventy percent of whom had received CDK4/6 inhibitors, met its primary progression-free survival endpoints in both the overall and the altered populations, and led to a 2023 FDA label restricted to the altered population, with diarrhoea, rash and hyperglycaemia as the main toxicities. OnCo links it to AKT and PIK3CA as targets, capivasertib, fulvestrant and Nicholas Turner. Final overall survival is awaited, and whether unaltered tumours benefit enough to widen the label is the open question.
Numbers are from the trial as recorded here; see the source links in the table below. This is orientation, not medical advice: ask your team how closely the trial population matches you.
708 randomised.
| Endpoint | Arm | n | Value | HR (95% CI) | p | Source |
|---|---|---|---|---|---|---|
| Progression-free survival (overall)primary | Capivasertib + fulvestrant | 355 | 7.2 months | 0.6 (0.51 to 0.71) | <0.001 | link |
| Placebo + fulvestrant | 353 | 3.6 months | ||||
| Progression-free survival (AKT-pathway-altered)primary | Capivasertib + fulvestrant | 155 | 7.3 months | 0.5 (0.38 to 0.65) | <0.001 | link |
| Placebo + fulvestrant | 134 | 3.1 months |
Shares PI3K, AKT and mTOR inhibitors, Capivasertib, Fulvestrant, AstraZeneca.
Shares PI3K, AKT and mTOR inhibitors, Capivasertib, Fulvestrant, AstraZeneca.
Shares PI3K, AKT and mTOR inhibitors, HR-positive metastatic breast cancer after CDK4/6 inhibitors, Fulvestrant, Hormonal therapy roadmap: removing the ovaries → tamoxifen → oral degraders switched by a blood test.
Shares AKT, PI3K, AKT and mTOR inhibitors, Capivasertib, Hormonal therapy roadmap: removing the ovaries → tamoxifen → oral degraders switched by a blood test.
Shares AKT, Capivasertib, Fulvestrant, PIK3CA / PI3K-alpha.
Shares PI3K, AKT and mTOR inhibitors, HR-positive metastatic breast cancer after CDK4/6 inhibitors, Fulvestrant, HR-positive / HER2-negative breast cancer.
Shares PI3K, AKT and mTOR inhibitors, Capivasertib, Fulvestrant, AstraZeneca.
Shares PI3K, AKT and mTOR inhibitors, HR-positive metastatic breast cancer after CDK4/6 inhibitors, Fulvestrant, HR-positive / HER2-negative breast cancer.