Efficacy and safety of dalpiciclib plus toremifene in advanced HR-positive HER2-negative breast cancer as first-line treatment: A multicenter, single-arm phase II trial.

e13062 Background: Dalpiciclib is a CDK4/6 inhibitor approved to treat metastatic hormone receptor-positive (HR+) breast cancer (mBC) in combination with endocrine therapy. Toremifene, a selective estrogen receptor modulator, has shown encouraging efficacy for HR+ mBC. Previous studies have demonstrated the effectiveness of combining CDK4/6 inhibitors with selective estrogen receptor modulators in reducing recurrence risk in early-stage breast cancer. This study aimed to evaluate the efficacy and safety of dalpiciclib combined with toremifene as first-line treatment for HR+/HER2- mBC. Methods: This multicenter, open-label, single-arm, phase II trial enrolled patients with HR+/HER2- advanced breast cancer (BC) who had not received prior therapy for mBC. Ovarian suppression was recommended for premenopausal women. The primary endpoint was progression-free survival (PFS). Secondary objectives included the objective response rate (ORR), clinical benefit rate (CBR), overall survival (OS) and safety. Results: From Jun 1, 2024, to January 15, 2025 (data cut-off), 26 patients were enrolled with 18 evaluable for efficacy. Among these, 17 had visceral metastasis. The median age was 59.5 years (range 45–73). The median follow-up was 7.5 months (range 8.63–NA). Median PFS was not yet reached. The overall ORR was 16.7%, with higher rate observed in patients with de novo mBC (39%) compared to those with recurrent BC (21%). CBR was 64% overall, with 78% in de novo mBC and 50% in recurrent BC. Best response per RECIST 1.1 included 16.7% of patients achieving partial response (PR), 77.8% with stable disease (SD), and 5.6% with progressive disease (PD). The most common adverse events (AEs) were decreased white blood cell count, neutropenia, generalized malaise, decreased lymphocyte count, constipation, and nausea. No grade 4 AEs occurred and grade 3 AEs included decreased white blood cell count (23.08%), neutropenia (23.08%), and decreased lymphocyte count (7.69%). Quality of Life (QoL) assessed via EORTC Measurement Scale QLQ-C30 (V3.0) showed a baseline mean global health status (GHS) score of 72.75. The mean scores in the functional domains (somatic, role, emotional, cognitive, and social) exceeded 90 after two treatment cycles. By the 6 th cycle, the mean GHS score improved by 7.78 points from baseline. Symptom domains including fatigue, nausea and vomiting, shortness of breath, insomnia, loss of appetite, constipation, and financial difficulties correlated with treatment cycles. Fatigue was the most reported symptom, indicating its impact on QoL. Conclusions: The combination of dalpiciclib and toremifene indicated a manageable, expected safety profile. This regimen may offer an viable first-line treatment option for HR+/HER2- mBC, especially for patients intolerant to aromatase inhibitors. Clinical trial information: NCT06495515 .