Recently, laboratory parameters have been explored as potential prognostic biomarkers in several tumour types. Here we present our findings in the population enrolled in the interim analysis of the DISTINCTIVE trial (NCT04252456), a prospectively stratified, biologically enriched phase II study of second-line FOLFIRI-aflibercept in RAS wild type (wt) metastatic colorectal cancer (mCRC) patients (pts) progressing after first-line anti-epidermal growth factor receptor (EGFR) drugs.
RAS wt mCRC pts resistant to first-line oxaliplatin-based chemotherapy + anti-EGFR are administered second-line FOLFIRI-aflibercept. Primary endpoint is overall survival (OS) according to VEGFR2 levels, whereas secondary endpoints are OS, progression free survival (PFS), response rate, safety and angiogenic factors levels. Clinical and laboratory data are collected to evaluate their correlation with outcome. Statistical analysis is performed with MedCalc (survival distribution: Kaplan-Meier; survival comparison: log-rank test; cut off: ROC curves).
Of 73 pts enrolled from 04/2018 to 06/2020, 44 were eligible for interim analysis. Among the laboratory values assessed, monocytes (M), red blood cells (RBC) and M/RBC ratio (MRR) were of particular interest. Better OS was related to lower (≤0.7x103/μl) M (14.2 months [95%CI:10.4-14.2] vs 6.8 months [95%CI:0.5-6.8], HR 0.003, p=0.0002) and higher (>3.81x106/μl) RBC (14.2 months [95%CI:10.4-14.2] vs 6.8 months [95%CI:0.5-9.1], HR 0.005, p< 0.0001). Longer PFS was correlated with lower M (8.5 months [95% CI:5.3-24.2] vs 4.2 months [95%CI:3.9-5.8], HR 0.18, p=0.0266) and higher RBC (8.5 months [95%CI:5.7-24.2) vs 2.5 months [95%CI:2.1-4.2], HR 0.04, p=0.0007). Lower MRR (≤1528) was related to improved OS (14.2 months [95%CI:10.4-14.2] vs 6.8 months [95%CI:0.5-6.8], HR 0.004, p=0.0003) and PFS (8.5 months [95%CI:5.3-24.2] vs 4.2 months [95%CI:3.9-5.8], HR 0.24, p=0.0492).
Our analysis confirmed the prognostic role of some haematologic parameters and an innovative and easy-to assess ratio in RAS wt mCRC pts receiving FOLFIRI-aflibercept.
Clinical trial identification
Legal entity responsible for the study
GISCAD (Gruppo Italiano per lo Studio dei Carcinomi dell'Apparato Digerente).
GISCAD; this study was partially supported by Sanofi Genzyme.
M. Scartozzi: Financial Interests, Personal, Advisory Board: Amgen; Sanofi; MSD; Eisai; Merck; Bayer; Financial Interests, Personal, Speaker’s Bureau: Amgen; Sanofi; MSD; Eisai; Merck; Bayer; Financial Interests, Personal, Other, Consultant: Amgen; Sanofi; MSD; Eisai; Merck; Bayer; All other authors have declared no conflicts of interest.