CAPItello-291 clinical trial

In this video, Prof Dr Javier Cortès comments on the poster he presented at SABCS 2024: “Prevalence of PIK3CA/AKT1/PTEN and other genomic alterations in primary and recurrent tumour tissue: an exploratory analysis from the Phase 3 CAPItello-291 clinical trial.”

The CAPItello-291 study is a Phase III trial that evaluated the efficacy of adding capivasertib to fulvestrant in patients with advanced breast cancer, specifically focusing on its impact on PFS. The trial targeted patients with PIK3CA-altered pathways, defined as mutations in PIK3CA, AKT, and/or PTEN, as well as the overall population (all-comers).

The results were encouraging. The primary endpoint, PFS, showed significant improvement in both groups. In the PIK3CA-altered pathway group, the hazard ratio was 0.50, indicating a 50% reduction in the risk of progression or death compared to fulvestrant alone. In the overall population, the hazard ratiio was 0.60, reflecting a 40% risk reduction. This underscores the strong efficacy of capivasertib in improving outcomes, particularly in patients with PIK3CA pathway alterations.

An exploratory biomarker analysis offered deeper insights. When comparing mutations between primary and metastatic samples, certain mutations such as AKT, PIK3CA, and PTEN were consistently present across both stages. However, other mutations appeared more frequently in either primary tumours or metastatic settings. For example, MAP3K and CDH1 mutations were observed more frequently in the PIK3CA-altered population, a pattern also noted in earlier studies like SOLAR-1.

This observation opens avenues for future research. The distinct mutation patterns in altered and non-altered populations suggest potential mechanisms of resistance to therapies like capivasertib. Exploring strategies to overcome resistance, such as combining drugs targeting multiple pathways, could optimise treatment. These findings emphasise the importance of integrating biomarker analyses into clinical trials, as they provide a framework for designing tailored and more effective therapeutic approaches.

In conclusion, CAPItello-291 highlights not only the therapeutic potential of capivasertib in combination with fulvestrant but also the value of biomarker-driven research in advancing precision medicine for breast cancer. Prospective trials that build on these findings could pave the way for more personalised and effective treatments.