Optimal treatment strategy in KRAS wild type (wt) metastatic colorectal cancer (mCRC): Cetuximab plus FOLFIRI followed by FOLFOX4 with or without cetuximab-The Capri trial from the Gruppo Oncologico Dell’Italia Meridionale (GOIM).

BACKGROUND: Cetuximab in combination with standard doublet chemotherapy is an effective treatment in KRAS wt mCRC patients (pts). The present study investigated a treatment strategy of cetuximab in combination with FOLFOX4 as a second line therapy for KRAS wt mCRC pts treated in first line with cetuximab plus FOLFIRI. METHODS: KRAS wt m CRC pts were treated in first line with cetuximab plus FOLFIRI and at progression were randomized (1:1) to receive FOLFOX alone (Arm A) or in combination with cetuximab (Arm B). Primary endpoint for each treatment line was progression-free survival (PFS), with secondary endpoints overall survival (OS), response rate (RR), disease control rate and safety. 221 events would be required to statistically differentiate PFS between the two arms with 80% power for the second line treatment. Here we report the results of first line cetuximab plus FOLFIRI treatment. RESULTS: From July 2009, 344 pts were enrolled: 58% males, median age 63 years (range, 20-81 years), ECOG performance status, 0 (85%); 1 (15%); synchronous metastasis (75%). For the 319 evaluable patients, median PFS was 10 months; overall response rate (ORR) was 55% with 47% partial responses (PR), 8% complete responses (CR) and 35% stable disease (SD) for a disease control rate (DCR) of 90%. The most common grade 3/4 adverse events were: skin reactions (15%), diarrhea (9%) and neutropenia (6%). As of January 31 2013, 118 pts have progressed and have been enrolled in second line treatment (58 Arm A; 60 Arm B). CONCLUSIONS: The results of first line treatment with cetuximab plus FOLFIRI confirm in a multicenter trial in prospectively selected KRAS wt mCRC pts the efficacy and tolerability of this combination. The randomized second line part of the study is currently ongoing. Multiple gene next generation sequencing to characterize a 24 genes mutation profile is currently ongoing. Clinical trial information: 2009-014041-81.