Capivasertib-paclitaxel fails to improve overall survival in metastatic TNBC

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Annals of oncology : official journal of the European Society for Medical Oncology Published May 1, 2026 Medically reviewed May 8, 2026 Study authors: Schmid P, McArthur H L, Cortés J, Xu B, Cardoso F, Casalnuovo M, Demirci U, Freitas-Junior R, Ghosh … PubMed ↗ DOI ↗ By Dr. Sofia Müller, MD · Lifespan & Whole-Person Care

Key Takeaway

Consider that capivasertib-paclitaxel did not significantly improve overall survival in metastatic TNBC despite PFS gains.

This global phase III randomized trial evaluated capivasertib 400 mg twice daily (days 2-5, weeks 1-3) plus paclitaxel 80 mg/m2 (day 1, weeks 1-3) versus placebo plus paclitaxel in 812 patients with previously untreated metastatic triple-negative breast cancer. The primary outcome was overall survival (OS) in the overall population and in patients with PIK3CA/AKT1/PTEN-altered tumours.

In the overall population, median OS was 17.7 months with capivasertib-paclitaxel versus 18.0 months with placebo-paclitaxel (HR 0.92; 95% CI 0.78-1.08; P=0.3239). In patients with PIK3CA/AKT1/PTEN-altered tumours, median OS was 20.4 months in both arms (HR 1.05; 95% CI 0.77-1.43; P=0.7602). Progression-free survival (PFS) numerically favored capivasertib-paclitaxel in the overall population (median 5.6 vs 5.1 months; HR 0.72; 95% CI 0.61-0.84) and in the altered subgroup (median 7.5 vs 5.6 months; HR 0.70; 95% CI 0.52-0.95).

Safety was generally manageable. Grade ≥3 diarrhea occurred in 12.7% of capivasertib-paclitaxel patients versus 0.7% with placebo-paclitaxel. Discontinuation rates were 8.5% versus 4.9%. Serious adverse events were not reported. Limitations include a short median follow-up of 0.9 months and lack of reported absolute differences.

Capivasertib-paclitaxel did not meet the prespecified boundary for improving OS in either population. While PFS improvements were observed, the lack of OS benefit limits clinical utility. These findings do not support routine use of this combination in previously untreated metastatic TNBC.

Study Details

Study typeRct

Sample sizen = 812

EvidenceLevel 2

Follow-up0.9 mo

PublishedMay 2026

PMID41422862

View Original Abstract ↓

BACKGROUND: Adding the pan-Akt serine/threonine kinase (AKT) inhibitor capivasertib to first-line paclitaxel in metastatic triple-negative breast cancer (TNBC) led to significantly longer progression-free survival (PFS) and overall survival (OS) versus placebo-paclitaxel in the phase II PAKT trial. CAPItello-290 was designed to further assess capivasertib-paclitaxel, including in patients with PIK3CA/AKT1/PTEN-altered tumours. PATIENTS AND METHODS: Patients with previously untreated metastatic TNBC were randomised 1 : 1 to paclitaxel 80 mg/m [day 1, weeks 1-3 (4-week cycle)] plus capivasertib 400 mg or placebo twice daily (days 2-5, weeks 1-3). PIK3CA/AKT1/PTEN alterations were analysed by retrospective central molecular testing. Dual primary endpoints were OS in the overall population and in patients with PIK3CA/AKT1/PTEN-altered tumours; investigator-assessed PFS was a key secondary endpoint. RESULTS: From July 2019 to February 2022, 812 patients were randomised; 30.7% of patients had PIK3CA/AKT1/PTEN tumour alterations. At final analysis [data cut-off (DCO) 18 March 2024], the median OS for the overall population was 17.7 and 18.0 months with capivasertib-paclitaxel and placebo-paclitaxel, respectively [hazard ratio (HR) 0.92, 95% confidence interval (CI) 0.78-1.08, P = 0.3239] and for patients with PIK3CA/AKT1/PTEN-altered tumours, it was 20.4 months in both arms (HR 1.05, 95% CI 0.77-1.43, P = 0.7602). At PFS DCO (25 May 2022), the median PFS in the overall population numerically favoured capivasertib-paclitaxel (5.6 versus 5.1 months placebo-paclitaxel; HR 0.72, 95% CI 0.61-0.84); this was also the case in patients with PIK3CA/AKT1/PTEN-altered tumours (7.5 versus 5.6 months placebo-paclitaxel; HR 0.70, 95% CI 0.52-0.95). The most frequent adverse event (AE) of grade ≥3 was diarrhoea [12.7% versus 0.7% placebo-paclitaxel (overall population)]. Capivasertib was discontinued due to AEs in 8.5% of patients (4.9% placebo-paclitaxel; overall population); AEs led to death in 4.2% of all patients. CONCLUSIONS: Capivasertib-paclitaxel did not meet the prespecified boundary for improving OS in either population; PFS numerically favoured the combination, especially in PIK3CA/AKT1/PTEN-altered tumours. The safety of capivasertib-paclitaxel was generally manageable and consistent with prior studies.