Journal Publication

Dalpiciclib plus endocrine therapy hits 92.5% six-month survival in visceral crisis

The DARVIN phase 2 trial met its primary endpoint in a population usually excluded from CDK4/6-inhibitor studies, with a cfDNA marker flagging who does worst.

The DARVIN phase 2 trial reported that dalpiciclib plus endocrine therapy produced a 92.5% six-month overall survival rate in HR-positive/HER2-negative advanced breast cancer patients with visceral crisis, meeting its primary endpoint.

By AppliedXLJuly 21, 2026Trial NCT05431504

Executive Summary

A phase 2 trial testing dalpiciclib, an oral CDK4/6 inhibitor, alongside endocrine therapy met its primary survival endpoint in a population of breast cancer patients experiencing organ-threatening disease flares, a group usually steered straight to chemotherapy rather than targeted therapy.
Visceral crisis, defined by symptomatic organ compromise from metastatic spread, is an exclusion criterion in most CDK4/6-inhibitor trials, so this single-arm study addresses a question the pivotal trials for this drug class never answered directly.
The survival benefit came with a high rate of severe blood-count suppression, a tolerability signal that carries added weight in patients whose organs are already compromised by their cancer.
A cfDNA-based biomarker distinguished patients at markedly higher risk of death within this cohort, a finding that, if confirmed, could help select which visceral crisis patients are appropriate for this approach versus chemotherapy.

The finding

Researchers from the Cancer Institute and Hospital, Chinese Academy of Medical Sciences, reported that dalpiciclib plus endocrine therapy met the primary endpoint of the DARVIN trial: a six-month overall survival rate of 92.5% (95% CI: 81.8-97.9), with 49 of 53 enrolled patients surviving past six months. The trial enrolled postmenopausal, premenopausal and perimenopausal women with HR-positive, HER2-negative advanced breast cancer experiencing visceral crisis, a state of symptomatic organ compromise from liver, lung, or bone marrow involvement that typically excludes patients from CDK4/6-inhibitor studies and pushes them toward chemotherapy instead. Dalpiciclib+1

Probability of Success

Endpoint Met25%

Completes67%

Clinical Significance17%

Regulatory89%

How it was done

The DARVIN trial was a multicenter, nonrandomized, open-label phase 2 study with a single treatment arm and no comparator, run in China. Fifty-three patients received oral dalpiciclib plus endocrine therapy, with the primary endpoint set as the six-month overall survival rate and nine prespecified secondary endpoints covering overall survival, progression-free survival, response rate, duration of response and safety. Patients with prior CDK4/6-inhibitor exposure, primary endocrine resistance, or more than three prior lines of endocrine therapy were excluded. NCT05431504

Beyond the primary endpoint

Secondary measures showed an objective response rate of 26.4%, a disease control rate of 79.2%, and a three-month treatment failure rate of 22.6%. Median progression-free survival reached 11.2 months (95% CI: 7.6-19.3) and median duration of disease control reached 14.1 months (95% CI: 8.4-21.5), while median overall survival had not been reached at the time of reporting. Those durability figures, in a population defined by acute organ-threatening disease, sit alongside the tolerability data as the two findings that carry the most weight for how this result should be read. Dalpiciclib

The safety tradeoff

The most common grade 3 or higher adverse events were decreased neutrophil count, in 77.4% of patients, and decreased white blood cell count, in 54.7%. Myelosuppression is an established class effect of CDK4/6 inhibitors, but the rate here occurred in patients whose organs were already compromised by their cancer at enrollment, raising the practical question of how closely blood counts need to be monitored in this specific subgroup versus the broader HR-positive population where dalpiciclib and similar agents are already used. Dalpiciclib

A biomarker signal

An exploratory analysis found that a baseline monocyte-derived circulating free DNA (cfDNA) level below 0.0581 was associated with worse overall survival, with a hazard ratio of 4.79 (95% CI: 1.05-45.47, P = 0.0394), a finding the authors described as marking a molecular crisis distinct from the clinical visceral crisis definition. The wide confidence interval reflects the small number of events behind it, but the signal offers a testable hypothesis for identifying which visceral crisis patients are most likely to fail this regimen early. Dalpiciclib

Where this sits in the field

Dalpiciclib already has an established evidentiary base in HR-positive, HER2-negative breast cancer outside visceral crisis, with other ongoing trials of the drug testing it in earlier lines and adjuvant settings. The competitive field around the CDK4/6 target is broad, spanning ribociclib, palbociclib, and abemaciclib along with newer entrants, but DARVIN is distinguished less by mechanism than by population: it tests the class specifically in patients that pivotal trials for this drug class have excluded. For that population, the working comparator is chemotherapy, not another CDK4/6 inhibitor, since no other identified trial in this class enrolls visceral crisis patients directly. NCT05431504

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