187O Capivasertib and fulvestrant for patients (pts) with aromatase inhibitor (AI)-resistant HR+/HER2– advanced breast cancer (ABC): Subgroup analyses from the phase III CAPItello-291 trial

Capivasertib is a potent, selective pan-AKT inhibitor. In the phase III CAPItello-291 trial in pts with AI-resistant, HR+/HER2– ABC, the addition of capivasertib to fulvestrant (fulv) significantly improved the dual primary endpoints of PFS in the overall (hazard ratio [HR] 0.60; 95% confidence interval [CI] 0.51–0.71; p<0.001) and AKT pathway-altered population (HR 0.50; 95% CI 0.38–0.65; p<0.001) compared with placebo plus fulv. Here we report PFS in key clinically relevant subgroups (data cut-off Aug 15, 2022). Pts were randomised 1:1 to receive fulv (500 mg IM on days 1 and 15 of cycle 1, and day 1 of each subsequent 28-day cycle) with either placebo or capivasertib (400 mg twice daily; 4 days on, 3 days off). Randomisation was stratified by the presence of liver metastases, prior use of CDK4/6 inhibitor (CDK4/6i) and region. Preplanned exploratory PFS analyses included prior use of CDK4/6i, prior chemotherapy (CT) for ABC, and presence of liver metastases. Overall, 708 pts were randomised to capivasertib-fulv (n=355) or placebo-fulv (n=353): 289 pts (40.8%) had AKT pathway-altered tumours; 496 pts (70.1%) had received prior CDK4/6i; 129 pts (18.2%) had received prior CT for ABC, and 306 pts (43.2%) had liver metastases. PFS benefit of capivasertib-fulv over placebo-fulv was broadly consistent across key clinical subgroups (Table). In cross-subgroup comparison, placebo-fulv efficacy was lower in pts with prior CDK4/6i exposure and pts with liver metastases. Findings in the AKT pathway-altered population were consistent with the overall population and will be presented.Table: 187OPFS in the overall populationnMedian PFS, months (95% CI)HR (95% CI) (unadjusted)Capivasertib-fulvPlacebo-fulvPrior CDK4/6iYes4965.5 (3.9–6.8)2.6 (2.0–3.5)0.62 (0.51–0.75)No21210.9 (7.4–13.0)7.2 (4.8–7.9)0.65 (0.47–0.91)Prior CT for ABCYes1293.8 (3.0–7.3)2.1 (1.9–3.6)0.61 (0.41–0.91)No5797.3 (5.6–8.2)3.7 (3.4–5.1)0.65 (0.54–0.78)Liver metastasesYes3063.8 (3.5–5.5)1.9 (1.8–1.9)0.61 (0.48–0.78)No4029.2 (7.4–11.1)5.5 (3.9–5.8)0.62 (0.49–0.79) Open table in a new tab Exploratory PFS analyses confirmed a consistent benefit of treatment with capivasertib-fulv vs fulv alone in clinically relevant subgroups, including pts with prior CDK4/6i exposure or liver metastases, subgroups with poor prognosis on fulv alone.