CAPItello-291
Trial question
What is the role of capivasertib/fulvestrant in patients with HR+ advanced breast cancer whose disease had progressed during or after previous aromatase inhibitor therapy?
Study design
Multi-center
Double blinded
RCT
Population
Characteristics of study participants
99.0% female
1.0% male
N = 708
708 patients (701 female, 7 male).
Inclusion criteria: patients with HR+ advanced breast cancer whose disease had progressed during or after previous aromatase inhibitor with or without previous CDK4/6 inhibitor therapy.
Key exclusion criteria: symptomatic visceral disease; ≥ 2 lines of endocrine therapy or ≥ 1 line of chemotherapy for unresectable locally advanced or metastatic disease; prior treatment with any chemotherapy, immunotherapy, immunosuppressant medication (other than corticosteroids), or anticancer agents within 3 weeks prior to study treatment initiation; clinically significant abnormalities of glucose metabolism; abnormalities in coagulation; pregnancy or lactation.
Interventions
N=355 capivasertib plus fulvestrant (capivasertib 400 mg BID given on an intermittent weekly dosing schedule plus fulvestrant 500 mg injections on day 1 of weeks 1 and 3 of cycle 1, and then on day 1 of week 1 of each cycle thereafter).
N=353 placebo plus fulvestrant (matching placebo BID given on an intermittent weekly dosing schedule plus fulvestrant 500 mg injections on day 1 of weeks 1 and 3 of cycle 1, and then on day 1 of week 1 of each cycle thereafter).
Primary outcome
Median progression-free survival in overall population
7.2 months
3.6 months
7.2 months
5.4 months
3.6 months
1.8 months
0.0 months
Capivasertib plus
fulvestrant
Placebo plus
fulvestrant
Significant
increase ▲
Significant increase in median progression-free survival in overall population (7.2 months vs. 3.6 months; HR 1.67, 95% CI 1.41 to 1.96).
Secondary outcomes
Significant increase in median progression-free survival in AKT pathway-altered population (7.3 months vs. 3.1 months; HR 2, 95% CI 1.54 to 2.63).
Significant increase in overall survival at 18 months in overall population (73.9% vs. 65%; HR 1.35, 95% CI 1.02 to 1.79).
Significantly longer median time to deterioration in global health status and QoL (24.9 months vs. 12 months; HR 1.43, 95% CI 1.09 to 1.89).
Safety outcomes
Significant differences in diarrhea (72.4% vs. 20.0%), rash (38.0% vs. 7.1%).
Conclusion
In patients with HR+ advanced breast cancer whose disease had progressed during or after previous aromatase inhibitor with or without previous CDK4/6 inhibitor therapy, capivasertib plus fulvestrant was superior to placebo plus fulvestrant with respect to median progression-free survival in overall population.
Reference
Nicholas C Turner, Mafalda Oliveira, Sacha J Howell et al. Capivasertib in Hormone Receptor-Positive Advanced Breast Cancer. N Engl J Med. 2023 Jun 1;388(22):2058-2070.
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