Lancet oncol: Can endocrine therapy with Pabosinib further improve prognostication in patients with early breast cancer?

Palbociclib (Pabosini) combined endocrine therapy can improve the progression-free survival of hormone-positive, HER2-negative metastatic breast cancer.
PALAS trial was designed to investigate whether pabosinib, which was added for 2 years in assisted endocrine therapy, could further improve the survival rate of hormone-positive, HER2-negative early breast cancer patients with non-invasive diseases compared to endocrine therapy alone.
PALLAS trial is an ongoing multi-center, open-label, randomized Phase 3 trial that recruited histologically diagnosed stage II-III hormone-positive, HER2-negative breast cancer patients in 406 cancer centers in 21 countries (and required to be in the group within 12 months of initial diagnosis).
The subjects were randomly divided into two groups (1:1) to receive Pabosini plus auxiliary endocrine therapy (thamoxyfen or aromatase inhibitors ±promostogen-promoting hormone-releasing hormone excitants) or simply assisted endocrine therapy.
end of the disease is the survival of non-invasive diseases.
September 1, 2015 - November 30, 2018, a total of 5,760 patients were randomly divided into two groups: 2,883 in the joint group and 2,877 in the single endocrine therapy group.
the scheduled second interim analysis, the medium follow-up was 23.7 months (IQR 16.9-29.2), with 170 and 181 survival events for non-invasive diseases in the joint and single endocrine treatment groups, respectively.
3-year non-invasive disease survival rates were 88.2% and 88.5%, respectively, in the joint group and the single endocrine therapy group (risk ratio 0.93, 95% CI 0.76-1.15, P=0.51).
as a test statistic to compare non-invasive survival rates between groups, exceeding the predetermined invalid boundaries, the Independent Data Monitoring Board recommended that the combined group of patients deactivate Pabosini.
most common level 3-4 adverse reactions were neogenic granulocyte reduction (combined group 61.3% vs single endocrine group 0.3%), lecemia (30.2% vs. 0.1%) and fatigue (2.1% vs 0.3%).
351 cases (12.4%) and 220 (7.6%) severe adverse reactions occurred in the joint group and single endocrine group, respectively.
treatment-related deaths.
scheduled secondary midterm analysis showed that two years of assisted endocrine therapy plus Pabosini treatment did not further improve the survival rate of non-invasive diseases in patients with early breast cancer on the basis of endocrine therapy alone.
based on the results of this study, the scheme is not recommended for application in this context.
follow-up and related studies are under way in patients with the trial.