IPATunity130

IPATunity130 (NCT03337724) was a double-blind placebo-controlled phase 3 trial whose cohort A randomised 255 taxane-eligible patients with PIK3CA, AKT1 or PTEN-altered measurable advanced triple-negative breast cancer and no prior chemotherapy for advanced disease 2 to 1 (168 to 87) between February 2018 and April 2020 to ipatasertib 400 mg on days 1 to 21 or placebo, both with paclitaxel 80 mg/m2 on days 1, 8 and 15 every 28 days. The primary endpoint, investigator-assessed progression-free survival, showed no difference (hazard ratio 1.02, 95 percent confidence interval 0.71 to 1.45; medians 7.4 versus 6.1 months), and final overall survival was 24.4 versus 24.9 months (hazard ratio 1.08, 0.73 to 1.58). Ipatasertib added grade 3 or worse diarrhoea (9 versus 2 percent) and dose reductions (39 versus 14 percent) with similar overall grade 3 or worse adverse events (51 versus 46 percent); exploratory PAM50 and Burstein subtype analyses were inconsistent. The randomised phase 2 LOTUS trial had suggested a progression-free survival gain in the biomarker-altered subgroup that this trial did not validate; with CAPItello-290 (capivasertib) it shows that PI3K, AKT or PTEN alteration does not select triple-negative tumours for AKT inhibition. UK sites (registry, 7): Velindre Cardiff, University Hospital Coventry, Beatson Glasgow, Royal Marsden London and Sutton, Derriford Plymouth, Royal Stoke.