Capivasertib (C) and fulvestrant (F) for patients (pts) with aromatase inhibitor (AI)-resistant HR+/HER2– advanced breast cancer (ABC): Characterization and management of common adverse events (AEs) from the phase 3 CAPItello-291 trial.

Abstract

1067 Background: In the CAPItello-291 trial in eligible pts with AI-resistant HR+/HER2– ABC, the addition of C (a potent, selective pan-AKT inhibitor) to F significantly improved PFS (primary endpoint) compared with placebo (P) in the overall (HR 0.60; 95% 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). We report a detailed analysis of AEs. Methods: Pts were randomized 1:1 to receive F (500 mg IM on days 1 and 15 of cycle 1, and day 1 of each subsequent 28-day cycle) with either P or C (400 mg BID; 4 days on, 3 days off). Pts with HbA1c <8.0% and diabetes not requiring insulin were eligible. Incidence, management, and time to onset were summarized for common AEs (>10% any grade and >2.0% grade ≥3; CTCAE v5.0). Results: Overall, 708 pts were randomized to C+F (n=355) vs P+F (n=353); safety population C+F (n=355) vs P+F (n=350). Baseline risk factors potentially associated with hyperglycemia were a history of diabetes in 34 pts (10%) in the C+F arm vs 20 pts (6%) in the P+F arm (baseline median [range] HbA1c 5.4% [4.0–8.3] vs 5.4% [3.9–7.7]), median weight 65.0 kg (34–150) vs 66.5 kg (37–147) and 54% vs 53% of pts overweight/obese in the C+F vs P+F arms, respectively. Common AEs were diarrhea, rash, and hyperglycemia; maximum AE grade was mostly 1/2 and led to low rates of discontinuation. In the C+F arm, medications for the management of AEs were used in 151/257 pts (59%) with diarrhea (mostly loperamide; n=135), 109/135 pts (81%) with rash (mostly antihistamines; n=75/topical corticosteroids; n=64), and 28/60 pts (47%) with hyperglycemia (mostly metformin; n=18). Conclusions: Diarrhea, rash, and hyperglycemia, the most commonly reported AEs associated with AKT pathway inhibition, occur early in treatment with C+F, are generally low grade and manageable, and are associated with low rates of dose modifications/discontinuations. Clinical trial information: NCT04305496 . [Table: see text]