Phase II trial of target-guided personalized chemotherapy in first-line metastatic colorectal.

Abstract

3543 Background: Chemotherapy (Ch) options for patients (pts) with colorectal cancer (CRC) have increased in the last years. However, there are no validated prospective molecular markers in CRC to select which agents are better to treat any individual case. The aim of this study was to determine the efficacy in terms of progression free survival (PFS) of a biomarker panel to guide treatment selection in this setting. Methods: Treatment naive, ECOG 0-1, metastatic CRC pts were accrued. Pts were prospectively analyzed with a predefined set of 10 molecular targets, including: KRAS, BRAF, and PI3K mutations and Topoisomerase-1(Top-1), ERCC-1, Thymidylate synthase (TS) and Thymidine phosphorylase (TP) expression by inmunohistochemistry ( IHC) performed in a tumor biopsy. Ch combination schema plus Cetuximab (C) or Bevacizumab (B) at standard doses was customized based on: Topo-1 +:Irinotecan (I). Topo-1- and ERCC-1 -:Oxaliplatin(O). Topo-1- and ERCC1 +:investigator option (I or O). TS -:Fluoropyrimidines (FP).TS +:No FP. TP -:5-FU, TP +:Capecitabine. Maintenance C or B treatment was allowed. Primary outcome measure was PFS. Results: 74 pts were accrued and all of them received biomarker guide treatment. All of them began personalized. Interim analysis on 61 pts (38 males, median age 65) showed.Topo-1 + in 33 pts (54%),ERCC-1- in 36( 59%) TS + in 44 (73%), TP – in 61 ( 100%), K-ras nativein 34 ( 55%), BRaf mutated in 2 (3,2%). With a median follow up time of 9,1 months (m). Median PFS (95% CI) is 8,6 (6,2-10,9) m, with a 41,3% (27,4-55,2) 12mPFS . Overall clinical benefit (Response + Stabilizations) was 74,5% (65,6-83,4).Toxicities Grade ≥ 3 included 18% neutropenia, 4,9% asthenia and 3,3% anemia. 12 pts (23%) received loco-regional treatment ( surgery or radiosurgery). Median Overall survival has not been reached. Conclusions: Target- Guided Personalized Ch in first line CRC pts is feasible and results in promising PFS with low toxicity. Update of final results and more detailed data will be presented. Clinical trial information: NCT01453257.