First-line capivasertib improves PFS but not OS in metastatic TNBC

First-line treatment with the AKT inhibitor capivasertib in combination with paclitaxel did not improve overall survival (OS) in patients with metastatic triple-negative breast cancer (TNBC), despite favouring response rate (ORR) and progression-free survival (PFS) in the phase 3 CAPItello-290 trial.

Capivasertib is an oral inhibitor of all 3 AKT isoforms and demonstrated, in combination with paclitaxel, promising results in patients with advanced/metastatic TNBC or HR+ breast cancer [1,2]. The phase 3 CAPItello-290 trial (NCT03997123) evaluated the effectiveness of first-line treatment with capivasertib in patients with metastatic TNBC.

CAPItello-290 enrolled 812 participants, previously untreated for metastatic disease. They were randomised 1:1 to first-line capivasertib/paclitaxel or placebo/paclitaxel [3]. The dual primary endpoint was OS in the overall population (n=404) and OS in the PIK3CA/AKT1/PTEN-altered population (n=249). Key secondary endpoints were PFS, ORR, and safety. Prof. Heather McArthur (UT Southwestern Medical Center, TX, USA) presented the results.

The primary endpoint of CAPItello-290 was not met. The median OS in the overall population was 17.7 months versus 18.0 months in the capivasertib and placebo arm, respectively (HR 0.92; P=0.32). The median OS in the PIK3CA/AKT1/PTEN-altered population was 20.4 months versus 20.4 months in the capivasertib and placebo arm, respectively (HR 1.05; P=0.76). The OS result could not be attributed to any specific (prespecified) subgroup.

Conversely, PFS numerically favoured capivasertib over placebo, both in the overall population and the PIK3CA/AKT1/PTEN-altered population. The median PFS in the overall population was 5.6 months versus 5.1 months in the capivasertib and placebo arm, respectively (HR 0.72). The median PFS in the PIK3CA/AKT1/PTEN-altered population was 7.5 months versus 5.6 months in the capivasertib and placebo arm, respectively (HR 0.70). In addition, ORR favoured capivasertib: 50.1% versus 37.6% (OR 1.68; 95% CI 1.27–2.23) in the overall population and 54.1% versus 41.9% (OR 1.63; 95% CI 0.99–2.72) in the PIK3CA/AKT1/PTEN-altered population.

“CAPItello-290 did not meet its endpoint,” Prof. McArthur concluded. These results prompted discussant Prof. Karen Gelmon (University of British Columbia, Canada) to wonder whether the AKT pathway is in fact an important driver in TNBC.

1. Schmid P, et al. J Clin Oncol. 2020;38:423-433.
2. Turner N, et al. N Engl J Med 2023;388:2058-2070.
3. Schmid P, et al. Capivasertib (C) + paclitaxel (P) as first-line treatment of metastatic triple-negative breast cancer (mTNBC): The CAPItello-290 phase III trial. Abstract LBA19, ESMO Congress 2024, 13–17 September, Barcelona, Spain.

 

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Posted on 4 November 2024