title: Second-line cetuximab/irinotecan versus oxaliplatin/fluoropyrimidines for metastatic colorectal cancer with wild-type KRAS.
abstract: 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 (CapeOX) 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 CapeOX until subsequent treatment cycles.
authors.affiliation: Department of Oncology, Asan Medical Center, Seoul, Korea.
authors.forename: Yong Sang
authors.initials: YS
authors.lastname: Hong
authors.forename: Hwa Jung
authors.initials: HJ
authors.lastname: Kim
authors.forename: Seong Joon
authors.initials: SJ
authors.lastname: Park
authors.forename: Kyu-Pyo
authors.initials: KP
authors.lastname: Kim
authors.forename: Jae-Lyun
authors.initials: JL
authors.lastname: Lee
authors.forename: Jin Hong
authors.initials: JH
authors.lastname: Park
authors.forename: Jong Hoon
authors.initials: JH
authors.lastname: Kim
authors.forename: Seok-Byung
authors.initials: SB
authors.lastname: Lim
authors.forename: Chang Sik
authors.initials: CS
authors.lastname: Yu
authors.forename: Jin Cheon
authors.initials: JC
authors.lastname: Kim
authors.forename: Ji Yeon
authors.initials: JY
authors.lastname: Baek
authors.forename: Sun Young
authors.initials: SY
authors.lastname: Kim
authors.forename: Tae Won
authors.initials: TW
authors.lastname: Kim
mesh_terms: D000328:Adult; D000368:Aged; D061067:Antibodies, Monoclonal, Humanized / Q000008:administration & dosage*; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D002166:Camptothecin / Q000008:administration & dosage / Q000031:analogs & derivatives*; D000068818:Cetuximab; D015179:Colorectal Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000401:mortality; D018572:Disease-Free Survival; D004334:Drug Administration Schedule; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage*; D006801:Humans; D000077146:Irinotecan; D008297:Male; D008875:Middle Aged; D009154:Mutation; D009362:Neoplasm Metastasis; D009944:Organoplatinum Compounds / Q000008:administration & dosage*; D000077150:Oxaliplatin; D011518:Proto-Oncogene Proteins / Q000235:genetics*; D016283:Proto-Oncogene Proteins p21(ras); D019233:Retreatment; D055815:Young Adult; D018631:ras Proteins / Q000235:genetics*
chemical_list: D061067:Antibodies, Monoclonal, Humanized; C117307:KRAS protein, human; D009944:Organoplatinum Compounds; D011518:Proto-Oncogene Proteins; D000077150:Oxaliplatin; D000077146:Irinotecan; D016283:Proto-Oncogene Proteins p21(ras); D018631:ras Proteins; D000068818:Cetuximab; D005472:Fluorouracil; D002166:Camptothecin