Capivasertib plus fulvestrant improves clinical outcomes in advanced breast cancer

December 2022 Cancer trials Nalinee Pandey

The addition of the novel, pan-AKT kinase inhibitor capivasertib to fulvestrant significantly prolongs the progression-free survival (PFS) in patients with hormone receptor-positive, HER2-negative breast cancer. These findings were recently presented at the San Antonio Breast Cancer Symposium.

A phase III randomised CAPItello-291 trial was conducted to investigate the efficacy and safety of capivasertib for breast cancer patients.

Study Design

The randomized, phase III CAPItello-291 trial enrolled 708 patients with histologically confirmed hormone receptor-positive, HER2-negative locally advanced or metastatic breast cancer. All the participants experienced disease progression or recurrence during or after aromatase inhibitor therapy, with or without a cyclin-dependent kinase 4/6 inhibitor. The enrolled participants were randomly (1:1) divided to receive fulvestrant and either capivasertib (n = 355) or placebo (n = 353). The study’s primary endpoint was the progression-free survival (PFS) in overall population and subgroup with altered AKT-pathway. The secondary points were overall survival (OS) and objective response rate (ORR).

Results

The researchers reported an extended PFS of 7.2 months in the capivasertib group than placebo (3.6 months, HR = 0.6; 95% CI, 0.51-0.71). Furthermore, a higher ORR was seen in the capivasertib arm compared to the control arm (22.9% vs. 12.2%).

Among the subgroup with AKT mutations (41%) too, an increased PFS (7.3 months vs 3.1 months; adjusted HR = 0.5; 95% CI, 0.38-0.65) and ORR (28.8% vs. 9.7%) was observed with administration of capivasertib. The remaining patients with no alteration in the AKT pathway also had longer PFS (7.2 months vs 3.7 months; HR = 0.7; 95% CI, 0.56-0.88) with capivasertib.

The AKT inhibitor capivasertib had a safe and manageable safety profile. The common grade 3 or higher adverse events included rash (12.1%), diarrhoea (9.3%) and hyperglycemia (2.3%). Further, more patients treated with capivasertib discontinued treatment than with placebo (13% vs 2.3%).

Conclusion

The results of the CAPItello-219 trial demonstrate the clinical efficacy and safety of capivasertib. Its combination with fulvestrant has the potential to become a treatment option for hormone receptor-positive advanced breast cancer patients.

Reference

Turner N, et al. Abstract GS3-04. Presented at: San Antonio Breast Cancer Symposium; Dec. 6-10, 2022.

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