P-276 Safety and Efficacy of mFOLFOX6 + Panitumumab Combination Therapy and 5-FU/LV + Panitumumab Combination Therapy in Patients with Chemotherapy-Naïve Metastatic Colorectal Cancer (SAPPHIRE)

Abstract

Background: In Japan, oxaliplatin/5-FU/leucovorin (mFOLFOX6) is the most frequent first-line chemotherapy backbone for metastatic colorectal cancer (mCRC). However, peripheral nerve disorders caused by oxaliplatin (OXA), part of mFOLFOX6 therapy, decrease patients' quality of life. For patients who discontinue OXA after taking it for a certain period with no peripheral nerve disorders, OXA re-introduction at a later stage may be an option. This «stop and go» OXA approach with 5-FU/leucovorin maintenance was explored in OPTIMOX-1 study and showed similar efficacy as with continuous OXA administration. The present study evaluates the safety and efficacy of mFOLFOX6 plus panitumumab induction with 5-FU/leucovorin+ panitumumab maintenance in first line mCRC patients. Methods: This phase II, multi-center, open-label, randomized, controlled study was designed to evaluate efficacy and safety in patients with chemotherapy-naïve, unresectable, advanced/recurrent KRAS wild-type colorectal cancer after 6 cycles of mFOLFOX6 + panitumumab combination therapy and subsequently assigning them to a group continuing mFOLFOX6 + panitumumab combination therapy (Group A) and a group in which OXA is discontinued and 5-FU/LV + panitumumab combination therapy is provided (Group B). Eligible patients will be treated with 6 cycles of mFOLFOX6 + panitumumab combination therapy. Patients for whom continuation of mFOLFOX6 + panitumumab combination therapy is appropriate on the basis of examination before the 7th cycle and imaging after the 6th cycle will be randomly assigned to either Group A or Group B at a ratio of 1:1. After randomization, Group A or Group B treatment will be continued until the criteria for discontinuation of treatment are met. The primary efficacy endpoint is progression-free survival (PFS) 9 months after the day of randomization. Secondary endpoints include PFS, overall survival, response rate, and time to treatment failure. Safety will be evaluated based on the incidence of adverse events and their severity, including the incidences of peripheral nerve disorders and skin disorders. Enrollment began in September 2014 and 100 pts after randomization will be recruited. The final analysis will be carried out when patients have been followed up for >24 months. This Phase II has been planned in order to elucidate the appropriate option for the treatment of mCRC. Clinical trial information: NCT02337946.