Capivasertib plus fulvestrant shows numerical overall-survival gain in PIK3CA/AKT1/PTEN-altered advanced breast cancer

The CAPItello-291 phase III trial enrolled 708 patients with advanced breast cancer and randomized them 1:1 to receive capivasertib (400 mg twice daily on a 4‑on/3‑off schedule) plus fulvestrant, or placebo plus fulvestrant, after progression on aromatase‑inhibitor therapy. More than half of the participants had previously been treated with CDK4/6 inhibitors.

Overall survival was essentially unchanged across the entire study population (hazard ratio 1.00). In the subgroup with PIK3CA, AKT1 or PTEN alterations, overall survival was numerically better with capivasertib (HR 0.83), though the difference did not reach statistical significance and the analysis had only 53 % power.

A more pronounced signal emerged among patients with altered tumors who had prior CDK4/6 inhibitor exposure, showing a median overall‑survival extension of 6.9 months (HR 0.78). The authors advise cautious interpretation of this finding.

Secondary endpoints after progression also favored the experimental arm, with a longer time to first subsequent chemotherapy-11 months versus 6 months in the altered‑tumor group, and 11 months versus 7 months overall.

Safety was consistent with known AKT‑inhibitor effects, the most common adverse events being diarrhea (77 %) and rash (41 %). Dose reductions occurred in 21.9 % of patients and treatment discontinuations due to adverse events in 6.5 %.