Adebrelimab in combination with dalpiciclib and endocrine therapy as neoadjuvant treatment for HR+/HER2- early breast cancer: an exploratory study.

BACKGROUND

Hormone receptor-positive (HR+)/HER2- breast cancer (BC) exhibits limited sensitivity to neoadjuvant chemotherapy, with low pathologic complete response (pCR) rates. While CDK4/6 inhibitors (CDK 4/6i) combined with endocrine therapy have demonstrated efficacy, the immunogenicity of HR+/HER2- tumors remains low, limiting the benefit of immunotherapy. Emerging evidence suggests potential synergy between CDK4/6 inhibition and immune checkpoint blockade. This study explores the neoadjuvant combination of adebrelimab, dalpiciclib, and endocrine therapy in patients with stage II-III HR+/HER2- BC.

METHODS

This single-arm, exploratory study enrolled postmenopausal women with histologically confirmed stage II-III HR+/HER2- BC. Eligible patients received neoadjuvant therapy comprising adebrelimab (1200 mg intravenously, day 1), dalpiciclib (125 mg orally, once daily on days 1-21), and letrozole. Treatment was administered over five 28-day cycles prior to surgery. The primary endpoint was total pCR (tpCR; defined as ypT0-is/ypN0).

RESULTS

Between October 2024 and March 2025 patients (median age 61.5 years) with stage II-III HR+/HER2- BC were enrolled. Most patients had T2 tumors (85%) and N1 disease (55%). All patients received ≥1 treatment cycle; 17 completed surgery. Radiological partial response was observed in 13 patients (65%), with an overall objective response rate (ORR) of 65%. One patient (5%) achieved tpCR. Three patients discontinued due to adverse events (AE; one death, one hepatitis, and one pneumonia). Common grade ≥ 3 AEs included neutropenia (50%), leukopenia (25%), and elevated liver enzymes.

CONCLUSION

This triplet regimen demonstrated modest clinical activity in HR+/HER2- early BC, with the safety profile of this regimen remains a concern and warrants particular attention in clinical practice.