Cetuximab plus irinotecan after irinotecan failure in elderly metastatic colorectal cancer patients: clinical outcome according to KRAS and BRAF mutational status

Crit Rev Oncol Hematol. 2011 Jun;78(3):243-51. doi: 10.1016/j.critrevonc.2010.06.003. Epub 2010 Jul 8.

Abstract

Background: Scarce data are available about safety and efficacy of cetuximab in elderly metastatic colorectal cancer (mCRC) patients.

Patients and methods: We retrospectively analysed 54 irinotecan-refractory mCRC patients aged≥70 years treated with cetuximab plus irinotecan and evaluated clinical outcome according to KRAS and BRAF mutational status.

Results: Median age was 73 years (70-82). Main grade 3-4 toxicities were skin rash (15%), diarrhea (19%) and neutropenia (13%). Irinotecan dose reduction was necessary in 39% of patients. Fifty-two (96%) patients were analysed for KRAS and BRAF status. The 29 KRAS wild-type patients achieved better RR (31% vs 4%; p=0.030) and median PFS (4.21 months vs 3.95 months; p=0.034; HR: 0.50, 95% CI: 0.27-0.95) when compared with KRAS mutated ones. RR (41% vs 3%; p=0.001) and mPFS (4.57 months vs 3.78 months, p=0.001; HR: 0.35, 95% CI: 0.19-0.66) were significantly higher among the 22 KRAS and BRAF wild-type patients compared to the 30 KRAS or BRAF mutated ones.

Conclusion: Cetuximab plus irinotecan has a favourable safety profile in elderly mCRC patients, but a reduced dose of irinotecan should be considered. Such a combination can be a useful option for elderly KRAS and BRAF wild-type patients.

MeSH terms

  • Aged
  • Aged, 80 and over
  • Antibodies, Monoclonal / administration & dosage
  • Antibodies, Monoclonal / adverse effects
  • Antibodies, Monoclonal / therapeutic use*
  • Antibodies, Monoclonal, Humanized
  • Antineoplastic Combined Chemotherapy Protocols / administration & dosage
  • Antineoplastic Combined Chemotherapy Protocols / adverse effects
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use*
  • Camptothecin / administration & dosage
  • Camptothecin / adverse effects
  • Camptothecin / analogs & derivatives*
  • Camptothecin / therapeutic use
  • Cetuximab
  • Colorectal Neoplasms / drug therapy*
  • Colorectal Neoplasms / genetics*
  • Colorectal Neoplasms / pathology
  • Female
  • Humans
  • Irinotecan
  • Male
  • Mutation / genetics
  • Neoplasm Metastasis
  • Proto-Oncogene Proteins / genetics*
  • Proto-Oncogene Proteins B-raf / genetics*
  • Proto-Oncogene Proteins p21(ras)
  • Retrospective Studies
  • Treatment Failure
  • ras Proteins / genetics*

Substances

  • Antibodies, Monoclonal
  • Antibodies, Monoclonal, Humanized
  • KRAS protein, human
  • Proto-Oncogene Proteins
  • Irinotecan
  • BRAF protein, human
  • Proto-Oncogene Proteins B-raf
  • Proto-Oncogene Proteins p21(ras)
  • ras Proteins
  • Cetuximab
  • Camptothecin