CAPItello-290 Trial of Capivasertib/Paclitaxel Fails to Improve OS in TNBC

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The phase 3 CAPItello-290 trial (NCT03997123) evaluating capivasertib (Truqap) combined with paclitaxel failed to meet its dual primary end points of improved overall survival (OS) compared with paclitaxel plus placebo in both the overall trial population of patients with locally advanced or metastatic triple-negative breast cancer (TNBC), as well as in a subgroup of patients with tumors harboring PIK3CA, AKT1, or PTEN alterations.¹

For safety, the combination of capivasertib with paclitaxel had a similar safety profile in this study compared with that of each agent alone. Additionally, no new safety signals were identified.

Full data from the study will be shared at a later time.

“Despite modest advances, triple-negative breast cancer remains one of the most challenging forms of disease to treat due to the lack of known actionable biomarker targets, and chemotherapy-based regimens continue to be the mainstay of treatment. While the CAPItello-290 trial results have not shown what we hoped, they provide important information to further understand this aggressive form of breast cancer where patients are in urgent need of new treatments,” said Peter Schmid, MD, Barts Cancer Institute, London, UK, and principal investigator for the trial, in a press release.

The phase 3, double-blind, randomized CAPItello-290 trial is assessing the safety and efficacy of capivasertib plus paclitaxel vs placebo and paclitaxel for the frontline treatment of patients with locally advanced/metastatic TNBC.²

A total of 923 adult patients were included in the study if they had histologically confirmed locally advanced or metastatic TNBC, an ECOG or World Health Organization performance status of 0 or 1, measurable disease according to RECIST 1.1, and a formalin-fixed paraffin-embedded tumor sample from primary/recurrent cancer.

The dual primary end points of the study are OS in the overall patient population and in a population of patients whose tumors have alterations in the PI3K/AKT pathway, including PIK3CA, AKT1, or PTEN alterations. Secondary end points include progression-free survival (PFS), investigator assessment of PFS2, overall response rate, safety and tolerability, duration of response, clinical benefit rate, and pharmacokinetics.

In addition to this trial, capivasertib is undergoing investigation in the phase 3 CAPItello-292 trial (NCT04862663) for the treatment of breast cancer and in the CAPItello-280 (NCT05348577) and CAPItello-281 (NCT04493853) trials for the treatment of prostate cancer in combination with docetaxel and abiraterone (Zytiga).¹

“We are committed to advancing science for patients in some of the most challenging cancers, including this heterogeneous subtype of breast cancer. While we are disappointed in the CAPItello-290 outcome, these results will further our understanding of the role of the PI3K/AKT pathway in breast cancer as we continue our clinical research across the [capivasertib] clinical development programme and across our pipeline,” added said Susan Galbraith, executive vice president, oncology research and development, AstraZeneca, in the press release.¹

REFERENCES:

1. Update on the CAPItello-290 phase III trial for Truqap plus chemotherapy in advanced or metastatic triple-negative breast cancer. News release. AstraZeneca. June 18, 2024. Accessed June 19, 2024. https://tinyurl.com/45z9h3fy

2. Capivasertib+paclitaxel as first line treatment for patients with locally advanced or metastatic TNBC (CAPItello-290). ClinicalTrials.gov. Updated January 17, 2024. Accessed June 19, 2024. https://classic.clinicaltrials.gov/ct2/show/NCT03997123