Purpose In LOTUS (NCT02162719), adding the oral AKT inhibitor ipatasertib to first-line paclitaxel for locally advanced/metastatic triple-negative breast cancer (aTNBC) improved progression-free survival (PFS; primary endpoint), with an enhanced effect in patients with PIK3CA/AKT1/PTEN -altered tumors (FoundationOne next-generation sequencing NGS assay). We report final overall survival (OS) results. Methods Eligible patients had measurable previously untreated aTNBC. Patients were stratified by prior (neo)adjuvant therapy, chemotherapy-free interval, and tumor immunohistochemistry PTEN status, and were randomized 1:1 to paclitaxel 80 mg/m 2 (days 1, 8, 15) plus ipatasertib 400 mg or placebo (days 1–21) every 28 days until disease progression or unacceptable toxicity. OS (intent-to-treat ITT, immunohistochemistry PTEN-low, and PI3K/AKT pathway-activated NGS PIK3CA/AKT1/PTEN -altered populations) was a secondary endpoint. Results Median follow-up was 19.0 versus 16.0 months in the ipatasertib–paclitaxel versus placebo–paclitaxel arms, respectively. In the ITT population ( n  = 124), median OS was numerically longer with ipatasertib–paclitaxel than placebo–paclitaxel (hazard ratio 0.80, 95% CI 0.50–1.28; median 25.8 vs 16.9 months, respectively; 1-year OS 83% vs 68%). Likewise, median OS favored ipatasertib–paclitaxel in the PTEN-low ( n  = 48; 23.1 vs 15.8 months; hazard ratio 0.83) and PIK3CA/AKT1/PTEN -altered ( n  = 42; 25.8 vs 22.1 months; hazard ratio 1.13) subgroups. The ipatasertib–paclitaxel safety profile was unchanged. Conclusions Final OS results show a numerical trend favoring ipatasertib–paclitaxel and median OS exceeding 2 years with ipatasertib–paclitaxel. Overall, results are consistent with the reported PFS benefit; interpretation within biomarker-defined subgroups is complicated by small sample sizes and TNBC heterogeneity.