Abstract PS5-04-03: Real world outcomes of use of Capivasertib in patients with HR positive HER2 negative metastatic breast cancer: A single center study

Abstract Introduction: Capivasertib in combination with Fulvestrant is approved for a second or later line treatment option for metastatic ER/PR positive HER2 negative breast cancer, for patients harboring one or more PIK3CA, AKT1, and PTEN alterations, especially after use of CDK4/6 inhibitors. These mutations are seen in ∼55% patients with HR+ mBC. There is limited real-world data on the use of the combination. The purpose of this analysis is to assess the real-world efficacy and safety of this regimen in patients with HR positive metastatic breast cancer. Methods: We conducted a single-center, IRB-approved retrospective chart review of patients diagnosed with metastatic breast cancer (mBC) who received capivasertib in combination with Fulvestrant, with the last follow-up date as of June 30, 2025. Patient-specific demographic, clinical, pathological, and treatment data were collected. Data was summarized using descriptive statistics. Time to treatment failure (discontinuation either because of progression or adverse effects) and PFS were calculated by the Kaplan-Meier method. Results: We identified 28 patients who received Capivasertib; median age - 57 years (IQR 49-66.5). 21 (75%) had PICK3CA, 5 (17.9%) PTEN, and 4 (14.3%) AKT1 mutation with 2 patients had both PICK3CA and PTEN mutation. All the patients had received prior CDK4/6 inhibitors and 11 had exposure to prior chemotherapy. The median follow-up was 7.6 months (IQR, 4.1-12.3) compared to 13 months (IQR 9·1-16·7) in CAPItello-291, with a median time to treatment failure of 5 +/- 0.5 months (5.8 months in CAPItello-291). Median PFS was 6 +/- 0.5 months (7.2 months in CAPItello-291). Treatment was discontinued in 19 (67.9%) patients due to disease progression and in 3 (10.7%) patients because of adverse effects. The reason for discontinuation was hyperglycemia, liver injury, and skin rashes. Medications were either discontinued or reduced for 10/28 (34%). Skin rash was the most common reason for dose reduction. 7/28 (25%) patients died by the last follow-up date, with 4/7 (57.1%) having prior exposure to chemotherapy. 4/7 (57.1%) Patients had either visceral or treated brain metastases before starting capivasertib. 1/4 (25%) of patients with treated brain metastasis and 3/15 (20%) with one or more visceral metastases died during the study period. Conclusion: In this single-center experience, the findings of CAPItello-291 was validated, that a combination of capivasertib and fulvestrant is an effective treatment in second or later-line therapy for metastatic HR+ HER2- breast cancer patients harboring AKT pathway alterations, with a similar discontinuation rate. Citation Format: V. Singh, A. Al-Alwan, S. Kabraji, E. Levine, V. Gupta. Real world outcomes of use of Capivasertib in patients with HR positive HER2 negative metastatic breast cancer: A single center study abstract. In: Proceedings of the San Antonio Breast Cancer Symposium 2025; 2025 Dec 9-12; San Antonio, TX. Philadelphia (PA): AACR; Clin Cancer Res 2026;32(4 Suppl):Abstract nr PS5-04-03.