Pooled Analysis of Clinical Outcome of Patients with Chemorefractory Metastatic Colorectal Cancer Treated within Phase I/II Clinical Studies Based on Individual Biomarkers of Susceptibility: A Single-Institution Experience

摘要: Patients with metastatic colorectal cancer (mCRC) refractory to standard therapies have a poor prognosis. In this setting, recruitment into clinical trials is warranted, and studies driven by selection according individual tumor molecular characteristics are expected provide added value. We retrospectively analyzed data from patients mCRC or following failure of who were enrolled phase I/II at the Niguarda Cancer Center based on presence specific profile represent target susceptibility experimental drug(s). From June 2011 May 2016, 2044 underwent screening. Eighty (3.9%) in ad hoc studies; median age was 60 years (range 36–86) number previous treatment lines five 2–8). Molecular exploited within these MGMT promoter hypermethylation (48.7%), HER2 amplification (28.8%), BRAF V600E mutation (20%), novel gene fusions involving ALK NTRK (2.5%). One patient (1%) had RECIST (Response Evaluation Criteria Solid Tumors) complete response (CR), 13 (16.5%) experienced partial (PR), 28 (35%) stable disease (SD). Median progression-free survival (PFS) 2.8 months 2.63–3.83), 24% displaying PFS >5 months. growth modulation index (GMI) 0.85 0–15.61) 32.5% GMI >1.33. KRAS exon 2 mutations found 38.5% patients, among 78 known status, those wild-type tumors longer than mutated (3.80 [95% CI 2.80–5.03] vs. 2.13 months 1.77–2.87], respectively, p = 0.001). overall (OS) 7.83 months 7.17–9.33) for all OS (7.83 7.33–10.80] 7.18 months 5.63–9.33], p = 0.06). This single-institution retrospective study indicates that heavily pretreated population approximately 4% display potential actionable context suitable therapeutic intervention. Application challenging but improves outcome even later treatment.