Second‐line cetuximab/irinotecan versus oxaliplatin/fluoropyrimidines for metastatic colorectal cancer with wild‐type KRAS

The goal of the present study was to compare the efficacy of the combination of cetuximab and irinotecan to the combination of oxaliplatin and fluoropyrimidines as second‐line chemotherapy in patients with irinotecan‐refractory and oxaliplatin‐naïve metastatic colorectal cancer ( mCRC ) harboring wild‐type KRAS . The study included 120 patients with mCRC who had progressed after irinotecan‐containing first‐line chemotherapy and were never treated with oxaliplatin; 40 patients with wild‐type KRAS were accrued prospectively in the experimental arm (arm A), and 80 patients accrued retrospectively were divided into control arms B ( n  =   46) and C ( n =  34) according to KRAS genotype. Second‐line treatments consisted of cetuximab plus irinotecan for arm A, and oxaliplatin plus either 5‐fluorouracil ( FOLFOX ) or capecitabine ( C ape OX ) for the control arms. The median progression‐free survival ( PFS ) was 8.3, 5.8 and 3.9 months, for arms A, B and C, respectively, with statistical significance favoring arm A ( P  = 0.007). Differences in overall survival did not reach statistical significance (18.3 vs 12.6 vs 12.9, P  = 0.138), although there was a trend toward longer overall survival in arm A. In terms of benefit from oxaliplatin‐containing regimens either as second‐line or third‐line therapy, the median PFS was 5.0 months in arms B and C as second‐line therapy, and 4.0 months in arm A as third‐line therapy, with no statistical significance ( P  = 0.385). Second‐line cetuximab plus irinotecan is a valid treatment strategy for mCRC patients with irinotecan‐refractory and oxaliplatin‐naïve tumors harboring wild‐type KRAS . Oxaliplatin‐containing chemotherapy resulted in equivalent PFS both as a second‐line and a third‐line therapy, enabling delay of the administration of FOLFOX and C ape OX until subsequent treatment cycles.