Abstract P2-09-28: Dalpiciclib plus endocrine therapy for visceral crisis in advanced breast cancer: a multicenter, prospective, external controlled phase 2 study

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Abstract Background: Patients with visceral crisis due to advanced breast cancer (ABC) have a poor prognosis, even with first-line chemotherapy. Visceral crisis has been a common exclusion criterion in clinical trials for patients with ABC. Thus, data on their efficacy in ABC patients with visceral crisis is limited. This study aims to explore the efficacy and safety of dalpiciclib plus ET in hormone receptor-positive, human epidermal growth factor receptor 2-negative (HR+/HER2−) ABC patients with visceral crisis. Methods: This multi-center, prospective phase 2 study used a Simon two-stage design to evaluate HR+/HER2− ABC patients with visceral crisis, defined as pleural effusion; ascites; abdominal pain from liver or peritoneal metastasis; dyspnea from pleural effusion or lymphangitic spread in the lungs; elevated liver enzymes (> 2 × ULN); rapid bilirubin increase (> 1.5 × ULN) without Gilbert syndrome or biliary obstruction; pathologically confirmed bone marrow metastasis; and hemoglobin < 100 g/dL. Patients were treated with dalpiciclib (150 mg/day for 21 days, followed by 7 days off) plus the investigator’s choice of ET (experimental group). If 9 or more subjects had survived at 6 months in the first stage, then 35 additional subjects would be enrolled. The null hypothesis would be rejected if 28 or more subjects out of a total of 53 had survived beyond 6 months. Results were compared to real-world data from an external control group receiving chemotherapy, which followed the same inclusion and exclusion criteria. Inverse probability of treatment weighting (IPTW) approach was used to estimate the average treatment effect on the treated (ATT). Variables in propensity-score-adjustment including age, ECOG, disease recurrence, number of metastatic sites, lines of prior treatment, and classification of visceral crisis. Primary endpoint was the 6-month survival rate. Secondary endpoints included but not limited to OS, PFS, 3-month treatment failure rate (TFR), time to treatment failure (TTF), duration of disease control (DDC), and safety. Results: Between February 2023 and May 2024, 17 of 18 patients in the experimental group survived 6 months of treatment in the first stage and proceeded to the next stage. Subsequently, an additional 35 patients were enrolled in the second stage. Of the 53 patients in total, 12 were not followed up for 6 months, while 37 survived 6 months, successfully rejecting the null hypothesis that the 6-month survival rate was ≤ 44%. In the external control group, 157 patients were included. After IPTW adjustment, the effective sample size was approximately 50 patients. Compared to the chemotherapy, dalpiciclib plus ET was associated with substantially longer PFS (median 9.03 months [95% CI 7.20-12.65] vs 4.63 months [95% CI 2.92, 5.65]; HR = 0.334 [95% CI 0.200-0.557], P < 0.001) and longer TTF (median 9.46 months [95% CI 6.41-12.48] vs 4.14 months [95% CI 2.53-5.13]; HR = 0.34 [95% CI 0.207-0.570], P < 0.001). The 3-month TFR in the experimental group (22.6% [95% CI 12.28-36.21]) was considerably lower than in the external control group (40.0% [95% CI 26.41-54.82], P = 0.0876). Median DDC was 8.67 months (95% CI 7.13-NE) in the experimental group, and 4.76 months (95% CI 3.65-6.05) in the external control group, respectively. Treatment-related adverse events occurred in 100% of patients in the experimental group and in 93.6% of patients in the external control group. Lower rates of abnormal liver function were observed in the dalpiciclib plus ET versus chemotherapy group (increased alanine aminotransferase: 17% vs. 28.7%; increased aspartate aminotransferase: 22.6% vs. 40.1%). Conclusions: Compared with chemotherapy, dalpiciclib plus ET promotes better PFS for patients with HR+/HER2− advanced breast cancer experiencing a visceral crisis, with a manageable safety profile. Clinical trial identification: NCT05431504 Citation Format: Hongnan Mo, Yuee Teng, Li Cai, Huihui Li, Xinhong Wu, Jing Yao, Yu Wang, Fei Ma. Dalpiciclib plus endocrine therapy for visceral crisis in advanced breast cancer: a multicenter, prospective, external controlled phase 2 study [abstract]. In: Proceedings of the San Antonio Breast Cancer Symposium 2024; 2024 Dec 10-13; San Antonio, TX. Philadelphia (PA): AACR; Clin Cancer Res 2025;31(12 Suppl):Abstract nr P2-09-28.

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