Schmid P, Abraham J, Chan S, et al. - Whether the addition of capivasertib (AKT inhibitor) to paclitaxel would afford a safe and efficacious first-line therapy for triple-negative breast cancer (TNBC), was determined in this double-blind, placebo-controlled, randomized phase II trial, named the PAKT trial. Participants were women (n = 140) with untreated metastatic TNBC. The participants were randomly allocated (1:1) to receive paclitaxel 90 mg/m² (days 1, 8, 15) with either capivasertib (400 mg twice daily) or placebo (days 2-5, 9-12, 16-19) every 28 days until progression of the disease or unacceptable toxicity. In the capivasertib plus paclitaxel arm vs placebo plus paclitaxel arm, the median progression-free survival (PFS) was 5.9 months vs 4.2 months, respectively, and the median overall survival (OS) was 19.1 months vs 12.6 months, respectively. Median PFS of 9.3 months and 3.7 months was reported in relation to capivasertib plus paclitaxel and placebo plus paclitaxel, respectively, in patients with PIK3CA/AKT1/PTEN-altered tumors (n = 28). Overall, a significantly longer PFS and OS was achieved with the addition of capivasertib to first-line paclitaxel therapy for TNBC. Patients with PIK3CA/AKT1/PTEN-altered tumors experienced more pronounced benefits.