FOLFIRI+bevacizumab induction chemotherapy followed by bevacizumab or observation in metastatic colorectal cancer, a phase III trial (PRODIGE 9 – FFCD 0802)

During the last 15 years, treatment of patients with metastatic olorectal cancer (mCRC) has undergone major improvements. irst-line treatment combination regimen with 5-fluorouracil and rinotecan (FOLFIRI) was associated with a significant increase in verall survival [1]. The addition of biological agents to chemotherpy, such as the anti-vascular endothelial growth factor and nti-epidermal growth factor receptor monoclonal antibodies evacizumab and cetuximab [2,3] increased survival compared o chemotherapy alone. The duration of first-line combination hemotherapy has been questioned because of toxicities during ong treatments, with a negative impact on patient quality of life. hree phase III studies evaluating sequential chemotherapy (firstine fluoropyrimidine monotherapy followed by second-line dual hemotherapy in case of progressive disease) revealed no survival dvantage compared to first-line combination [4–6]. Therefore, a step-up” strategy became an option in mCRC but has never been valuated with regimens including biological agents. To avoid toxicities, the concept of chemotherapy-free intervals CFIs) as a “top-down” strategy was proposed in different studies 7,8]. In the study by Labianca et al., the experimental arm was the epetition of sequences consisting of 2 months with FOLFIRI folowed by 2 months without chemotherapy, even in the absence f tumour progression [8]: overall survival was the same comared to the arm with continuous chemotherapy. In the OPTIMOX I study, chemotherapy was re-introduced only in case of progresion based on baseline status, and this strategy was less efficient han continuous chemotherapy [7]. Further to these two trials, an lternative therapy is the re-introduction of chemotherapy as soon s progression is detected, i.e. based on last tumour assessment uring chemotherapy; this could increase survival and allow longer