Early tumor shrinkage in patients with metastatic colorectal cancer receiving first-line treatment with cetuximab combined with either CAPIRI or CAPOX: an analysis of the German AIO KRK 0104 trial

Acta Oncol. 2013 Jun;52(5):956-62. doi: 10.3109/0284186X.2012.752580. Epub 2012 Dec 18.

Abstract

Purpose: This study investigated the impact of early tumor shrinkage (ETS) on progression-free- (PFS) and overall survival (OS) in patients with metastatic colorectal cancer (mCRC) treated within the AIO KRK 0104 trial as first-line therapy. Moreover, correlations of ETS with clinical characteristics and prognostic markers were evaluated.

Patients and methods: In total, 121 patients were included into this analysis. Patients were treated with cetuximab combined with either CAPIRI or CAPOX. ETS at six weeks was defined as a relative change of ≥ 20% in the sum of the longest diameters of target lesions compared to baseline. Survival times were compared between patients with ETS ≥ 20% versus no-ETS.

Results: ETS ≥ 20% was observed in 59% of all patients with KRAS wild-type tumors. In these patients ETS ≥ 20% was associated with higher overall response rate (82% vs. 19%, p < 0.001). Also, PFS (8.9 vs. 4.7 months, p < 0.001) and OS (31.6 vs. 15.8 months, p = 0.005) were significantly superior in ETS ≥ 20% of patients compared to no-ETS. In patients with KRAS mutant mCRC ETS ≥ 20% neither had an effect on PFS nor OS. Cetuximab-induced skin toxicity correlated with the occurrence of ETS ≥ 20% (p = 0.002).

Conclusion: In patients with KRAS wild-type tumors treated with cetuximab plus capecitabine-based chemotherapy ETS ≥ 20% is an important predictor of favorable outcome.

Publication types

  • Clinical Trial, Phase II
  • Multicenter Study
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Antibodies, Monoclonal, Humanized / administration & dosage
  • Antineoplastic Combined Chemotherapy Protocols / administration & dosage
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use*
  • Camptothecin / administration & dosage
  • Camptothecin / analogs & derivatives
  • Capecitabine
  • Cetuximab
  • Colorectal Neoplasms / drug therapy*
  • Colorectal Neoplasms / genetics
  • Colorectal Neoplasms / pathology
  • Deoxycytidine / administration & dosage
  • Deoxycytidine / analogs & derivatives
  • Disease-Free Survival
  • Drug Combinations
  • Female
  • Fluorouracil / administration & dosage
  • Fluorouracil / analogs & derivatives
  • Humans
  • Male
  • Middle Aged
  • Mutation
  • Organoplatinum Compounds / administration & dosage
  • Oxaliplatin
  • Proto-Oncogene Proteins / genetics
  • Proto-Oncogene Proteins p21(ras)
  • Treatment Outcome
  • Tumor Burden*
  • ras Proteins / genetics

Substances

  • Antibodies, Monoclonal, Humanized
  • Drug Combinations
  • KRAS protein, human
  • Organoplatinum Compounds
  • Proto-Oncogene Proteins
  • Oxaliplatin
  • Deoxycytidine
  • Capecitabine
  • Proto-Oncogene Proteins p21(ras)
  • ras Proteins
  • Cetuximab
  • Fluorouracil
  • Camptothecin

Supplementary concepts

  • capecitabine-irinotecan combination