Background: In LOTUS (NCT02162719), adding the oral AKT inhibitor IPAT to first-line PAC for mTNBC improved progression-free survival (PFS; primary endpoint) [Kim, Lancet Oncol 2017]. The stratified PFS hazard ratio (HR) in the intent-to-treat (ITT) population (n = 124) was 0.60 (95% CI 0.37–0.98; p = 0.037; median PFS 6.2 vs 4.9 months with IPAT vs PBO, respectively). In prespecified analyses of patients (pts) with PIK3CA/AKT1/PTEN-altered tumors, the unstratified PFS HR was 0.44 (95% CI 0.20–0.99; median 9.0 vs 4.9 months). We now report updated OS results in the ITT population after OS events in ~50% of pts. OS results in the PIK3CA/AKT1/PTEN-altered subgroup are immature. Methods: Eligible pts had measurable inoperable mTNBC previously untreated with systemic therapy. Pts were stratified by prior (neo)adjuvant therapy, chemotherapy-free interval (6–12 months vs > 12 months vs not applicable) and tumor IHC PTEN status, and randomized 1:1 to PAC 80 mg/m² (d1, 8, & 15) with either IPAT 400 mg or PBO (d1–21) q28d until progression or unacceptable toxicity. OS was a prespecified secondary endpoint. Results: The table shows results after 23 months’ follow-up (data cutoff 26 July, 2017). No new safety signals were seen. Conclusions: The previously observed PFS improvement with IPAT was followed by a trend toward improved OS (~5-month difference in the medians) at the updated OS analysis. Post-progression therapy was similar. These findings support further evaluation of first-line IPAT + PAC for mTNBC in the ongoing IPATunity130 (NCT03337724) randomized phase 3 trial. Final OS results from LOTUS are expected in 2019. Clinical trial information: NCT02162719

^an = 61 in IPAT + PAC arm