Dalpiciclib plus endocrine therapy in women with HR+/HER2− advanced breast cancer and visceral crisis: a multicenter, nonrandomized, phase 2 DARVIN trial

Visceral crisis in advanced breast cancer (ABC) represents a major challenge. Here we conducted a phase 2 study to evaluate dalpiciclib plus endocrine therapy (ET) in women with HR+/HER2− ABC experiencing visceral crisis.
The primary endpoint was the 6-month survival rate; secondary endpoints included overall survival (OS), progression-free survival (PFS), time to treatment failure (TTF), 3-month treatment failure rate (TFR), duration of disease control (DDC), objective response rate (ORR), disease control rate (DCR) and safety. Among 53 participants, 49 survived beyond 6 months, yielding a 6-month survival rate of 92.5% (95% confidence interval (CI): 81.8–97.9), meeting the primary endpoint.
The ORR was 26.4%, DCR was 79.2% and 3-month TFR was 22.6%.
The median PFS was 11.2 months (95% CI: 7.6–19.3), DDC was 14.1 months (95% CI: 8.4–21.5) and TTF was 10.2 months (95% CI: 6.4–15.6); the median OS was not reached.
The most common grade ≥3 adverse events were neutrophil count decreased (77.4%) and white blood cell count decreased (54.7%). Exploratory analyses indicated that a baseline monocyte-derived cfDNA level below 0.0581 was associated with worse OS (hazard ratio: 4.79, 95% CI: 1.05–45.47, P = 0.0394), indicating a ‘molecular crisis’.
These findings support further evaluation of dalpiciclib plus ET in persons with ABC with visceral crisis (ClinicalTrials.gov: NCT05431504).