KEY TAKEAWAYS
- The CAPItello-291 phase III trial aimed to refine the understanding of PFS within the AKT pathway-altered population by analyzing outcomes by individual genes affected.
- The results demonstrated that capivasertib combined with fulvestrant consistently prolonged PFS across all three key AKT pathway gene alterations in HR+/HER2-negative advanced breast cancer.
In the CAPItello-291 Phase 3 trial, Sacha Howel and his research team aimed to analyze the progression free survival (PFS) in response to capivasertib, a potent pan-AKT inhibitor, combined with fulvestrant compared to placebo + fulvestrant in patients with aromatase inhibitor-resistant, hormone receptor-positive/human epidermal growth factor receptor 2-negative advanced breast cancer.
Patients were randomly assigned in a 1:1 ratio to receive fulvestrant (500 mg intramuscularly on days 1 and 15 of cycle 1, and day 1 of each subsequent 28-day cycle) along with either placebo or capivasertib (400 mg twice daily; 4 days on, 3 days off). AKT pathway-alteration status, determined post-randomization using next-generation sequencing in tumor tissue, required at least one qualifying alteration in the genes PIK3CA, AKT1, or PTEN. HRs were calculated employing Cox proportional hazards models.
Among the 708 randomized patients, 41% (n=289) had AKT pathway-altered tumors (capivasertib-fulvestrant n=155; placebo-fulvestrant n=134). In this population, 43% had liver metastases, and 40% exhibited primary endocrine therapy resistance. Prior therapy for advanced disease included: ≥1 line in 89% of patients, prior cyclin-dependent kinase 4 and 6 inhibitors in 71%, and prior chemotherapy in 18%. Baseline characteristics were well-balanced between treatment groups.
Majority of AKT pathway-altered tumors (94%) exhibited a single detectable alteration (272/289). Co-occurring alterations included PIK3CA and PTEN in 13 patients (capivasertib-fulvestrant n=4; placebo-fulvestrant n=9) and PIK3CA and AKT1 in four patients (capivasertib-fulvestrant n=2; placebo-fulvestrant n=2). Capivasertib-fulvestrant demonstrated consistent PFS benefit over placebo-fulvestrant across all alterations. The safety profile of capivasertib-fulvestrant in the AKT pathway-altered population remained consistent with the overall population.
The study found that capivasertib significantly boosted PFS across all key AKT pathway genes in HR+/HER2-negative ABC compared to fulvestrant alone. The research is sponsored by AstraZeneca.
Source: https://atgproductions.net/atgclients/sabcs/2023_SABCS_Abstract_Report-12-1-23_Compressed.pdf
Clinical Trial: https://clinicaltrials.gov/study/NCT04305496
Howell S, Rugo H, Oliveira M, et al.(2023)’’Capivasertib and fulvestrant for patients with aromatase inhibitor-resistant HR positive/HER2-negative advanced breast cancer: exploratory analysis of PFS by AKT pathway gene from the Phase 3 CAPItello-291 trial.’’ Presented at SABCS 2023 (PS17-03)
