Multicenter phase 2 trial of dalpiciclib plus endocrine therapy in women with HR+/HER2- advanced breast cancer and visceral crisis

Visceral crisis in advanced breast cancer (aBC) represents a major challenge. The multicenter phase 2 DARVIN trial in China evaluated the combination of dalpiciclib and endocine therapy (ET) in women with HR+/HER2- aBC experiencing visceral crisis. The primary endpoint was 6-month survival rate. Among 53 patients, 49 survived beyond 6 months, yielding a 6-month survival rate of 92.5% (95% CI 81.9-97.9), meeting the primary endpoint. The objective response rate was 26.4%, the disease control rate was 79.2%, and the 3-month treatment failure rate was 22.6%. The median progression-free survival was 11.2 months (95% CI 7.6-19.3), the median duration of disease control was 14.1 months (8.4-21.5), the median time to treatment failure was 10.2 months (6.4-15.6), and the median overall survival was not reached. The most common grade ≥3 adverse events were decrease of neutrophil count (77.4%) and of white blood cell count (54.7%). Exploratory analyses indicated that a baseline monocyte-derived cfDNA level below 0.0581 was associated with worse OS (HR 4.79; p=0.0394), indicating a ‘molecular crisis’. The authors conclude that these findings support further evaluation of dalpiciclib plus ET in patients with aBC with visceral crisis.