Statistical methods
death, tumour, neutropenia
DISEASE PROGRESSION, METASTASIS, LIVER METASTASES, NEUTROPENIA, MUTANT, LUNG METASTASES, TUMOUR, REGRESSION
Descriptive statistics were used to summarise baseline patient and clinical characteristics, TEAEs, ECOG PS, and QoL. Median and 95% confidence intervals (CIs) were reported for survival analyses and were estimated using the Kaplan-Meier method. For the PFS analysis, patients without disease progression or death before or at the last visit (including patients withdrawn for commercial availability), were censored at the date of the last evaluable tumour assessment. For the time to ECOG PS deterioration analysis, patients not reaching an ECOG PS of ≥2 and not dead, were censored at the last recorded ECOG PS assessment.A Cox proportional hazards model with time-dependent variable was used to explore the association between neutropenia and PFS. A Cox proportional hazards model including a stepwise selection process (including/retaining factors significant at the 10% level; Wald chi-square test) was used to explore potential prognostic factors for PFS. Factors considered for inclusion in the model were: time since diagnosis of the 1st metastasis (< 18 versus ≥18 months); number of metastatic sites (1–2 versus ≥3); ECOG PS (0 versus 1); presence of liver metastases (yes versus no); presence of lung metastases (yes versus no); presence of lymph node metastases (yes versus no); BMI group (< 18.5 versus ≥18.5; < 25 versus ≥25; < 30 versus ≥30); RAS status (wild versus mutant); side of primary tumour site (right versus left); gender (male versus female); age group (< 70 years versus ≥70 years); previous treatment with an anti-VEGF (yes versus no); previous treatment with regorafenib (yes versus no); and baseline haemoglobin (< 110 versus ≥110 g/l), white blood cell count (< 10 versus ≥10 × 10A logistic regression model including a stepwise selection process was used to explore risk factors for neutropenia, with the same factors as for PFS described above with the addition of number of previous lines of treatment (≤2 versus > 2).All statistical analyses were performed using SAS (V.9.2) software under the responsibility of Global Biostatistics of the sponsor (I.R.I.S).