Statistical analyses
tumor
TUMOR, LIVER METASTASES, PRIMARY TUMOR, EVENT, METASTATIC DISEASE, SECONDARY, REGRESSION
The primary endpoint was the confirmed ORR evaluated by investigator assessment using RECIST 1.1. The secondary endpoints included duration of response, PFS, OS and clinical benefit rate evaluated on the FAS and per cohort. Safety was evaluated on the safety population and per cohort. The required number of assessable patients for cohort 1 (The primary endpoint was reported for each cohort, and comparisons were considered exploratory. Comparison between cohorts was performed using the chi-square test or Fisher’s exact test for qualitative variables and the Kruskal–Wallis test for continuous variables; and multivariable analysis was performed using logistic regression model adjusted for hormone receptor status of primary tumor (hormone receptor-positive versus hormone receptor-negative), time from initial diagnosis to metastatic disease (0–3 months versus >3 months), time from diagnosis of metastatic disease to inclusion (0–24 months versus 24–60 months versus >60 months), number of metastatic sites (<3 versus ≥3 sites), presence of liver metastases (yes versus no) and ECOG performance status (0 versus 1) at inclusion. ORs were estimated with corresponding 95% CI. The best tumor shrinkage of target lesions was plotted on a waterfall plot and compared between cohorts using the Kruskal–Wallis test. Time to event endpoints (PFS and duration of response) were estimated using the Kaplan–Meier method, and comparison between groups was performed using the log-rank test. Multivariable analysis was performed using Cox proportional hazards model adjusted for the same variables used for the confirmed objective response. HRs were estimated with corresponding 95% CI. In the exploratory objective of modulation of tumor microenvironment, comparisons of each biomarker at baseline and on-treatment were performed using the Wilcoxon matched-pairs signed-rank test. Cell distance analysis 