• mCRC

The present work focuses on clinical and translational results from the no-profit phase III randomized TRIPLETE trial conducted by the Gruppo Oncologico del Nord Ovest (GONO) and coordinated by the Unit of Medical Oncology 2 at the Azienda Ospedaliero-Universitaria Pisana. The study aimed at comparing the efficacy of a preplanned strategy of upfront exposure to the three cytotoxic drugs in the modified FOLFOXIRI (fluorouracil, leucovorin, irinotecan and oxaliplatin) regimen plus panitumumab respect to the standard of treatment with mFOLFOX6 + panitumumab in previously untreated metastatic colorectal cancer patients.
The first chapter of the present thesis describes the current landscape of the first-line treatment of metastatic colorectal cancer patients, with a particular focus on the use of intensified treatment strategies and previous experiences during the last years about this topic. The aim of this chapter is to provide the reader with a frame to properly understand the background of the design of the TRIPLETE trial and the unmet needs that the study attempted to address.
The second chapter focuses on potential role of translational analyses in a target treatment such that used in the TRIPLETE trial: current evidences on resistance mechanisms are exposed to underline how could the molecular selection improve the correct selection and clinical management of our patients both at baseline and during the treatment. Moreover, an in-depth analysis of the potential role of cfDNA in anticipate the insurgence of resistance mechanisms is described.
Finally, the third chapter describes clinical and translational results of project moving from the TRIPLETE study: a comprehensive genomic profiling by means of a next-generation sequencing (NGS) approach both on tissue and blood samples. Other translational projects including samples from patients enrolled in the TRIPLETE study are currently ongoing and will help to throw light on the complex molecular landscape of metastatic colorectal cancer and on the optimization of the treatment based on anti-EGFRs, by an improved selection of candidate patients potentially resistant to this strategy.