Single center study of efficacy and safety of capivasertib in hormone receptor–positive (HR+), HER2-negative metastatic breast cancer (MBC).

Abstract

e13101 Background: Capivasertib and alpelisib have shown efficacy in clinical trials of HR+/HER2- MBC when used in patients (pts) with PI3K pathway alterations after progression on endocrine therapy. However, gaps remain in understanding their real-world efficacy and safety, particularly for capivasertib in pts whose clinical characteristics differ from trial populations and those previously treated with alpelisib. Methods: We conducted a retrospective analysis of 34 HR+/HER2- MBC pts treated with capivasertib at Moffitt Cancer Center after its approval in 11/2023. The primary endpoint was progression-free survival (PFS), defined as the time from capivasertib initiation to radiographic progression, last follow-up, or death. Secondary endpoints included PFS without (PFS1) and with prior alpelisib treatment (PFS2) and the adverse effects (AE) of capivasertib. Results: Median age of pts at capivasertib initiation was 61 years (range: 31–74). Most were Caucasian (88.2%), had ECOG performance status 0–1 (93.9%), and presented with HR+/HER2-low disease (73.5%). At capivasertib initiation, 85.3% had bone metastases, 76.5% had visceral disease, and 17.6% had brain metastases. Median number of prior therapies in the metastatic setting was 2 (range: 1-9). All pts were treated with CDK4/6 inhibitors, 44.1% received prior T-DXd, and 44.1% received other chemotherapy. Thirteen pts (38.2%) had been treated with alpelisib, including two who transitioned to capivasertib without intervening therapies. Thirteen pts remain on treatment with capivasertib as of data cut off on 1/24/2025. Most common mutations in PI3K pathway included- PIK3CA (85.3%), AKT (23.5%), and PTEN (17.6%). Additionally, 26.5% had co-mutations in ESR1. Four pts had partial response and 6 had stable disease (3 had durable response > 24 weeks) as best overall response. With a median follow-up of 6 months (range: 0.9–13 months), the median PFS was 3.5 months (95% CI 2.4-7.6) for the entire group. Median PFS1 (6.3 months, 95% CI 2.3-NR) and median PFS2 (3.4 months, 95% CI 2.4-NR) were comparable (HR 0.75, 95% CI 0.31–1.82, p = 0.53). The most common AE of any grade attributed to capivasertib included diarrhea (52.9%), nausea (35.3%), loss of appetite (35.3%), fatigue (29.4%), and hyperglycemia (14.7%). Grade ≥3 AE were limited to diarrhea and hyperglycemia, each occurring in one pt. Dose interruptions and reductions due to AE were required in 9.4% and 6.3% of pts, respectively. Conclusions: Our findings suggest that capivasertib could be an option for pts previously treated with alpelisib, with a manageable toxicity. The shorter PFS observed in our study compared to the CAPItello-291 trial is likely due to relatively short follow-up period, with 13 pts still on treatment at last follow-up, and the inclusion of a heavily pretreated population, many of whom had received multiple lines of chemotherapy, including T-DXd.