Outcomes of Older Patients (≥ 70 Years) Treated With Targeted Therapy in Metastatic Chemorefractory Colorectal Cancer: Retrospective Analysis of NCIC CTG CO.17 and CO.20

Clin Colorectal Cancer. 2019 Mar;18(1):e140-e149. doi: 10.1016/j.clcc.2018.11.006. Epub 2018 Nov 28.

Abstract

Background: The safety and efficacy of targeted therapy in older patients (≥ 70 years) with metastatic colorectal cancer is not well evaluated.

Patients and methods: Outcomes of older patients (including overall survival [OS], progression-free survival [PFS], toxicity, and quality of life [QoL]) were compared to young patients using data from 2 large previously reported clinical trials, CO.17 (cetuximab vs. best supportive care) and CO.20 (cetuximab plus placebo vs. cetuximab plus brivanib). Only patients with wild-type KRAS tumors were included.

Results: A total of 251 (26.3%) of 955 patients were ≥ 70 years old. No significant differences in OS, PFS, or grade 3/4 adverse events were observed between older and younger patients treated with cetuximab (or cetuximab with placebo) in either trial. Younger patients trended toward superior OS in both CO.17 (hazard ratio = 1.80; P = .16) and CO.20 (hazard ratio = 1.34; P = .07). QoL maintenance favored younger patients in CO.17 (3.6 vs. 5.7 months; P = .046) but no difference of QoL maintenance was observed in the larger CO.20 trial (1.7 vs. 1.8 months; P = .64). Combination therapy of cetuximab and brivanib was significantly more toxic in older adults (87% vs. 77%; P = .03).

Conclusion: OS, PFS, and toxicities were similar between older and younger patients with wild-type KRAS metastatic colorectal cancer when treated with cetuximab. Both age groups likely experience similar QoL maintenance with cetuximab. Dual targeted therapy was significantly more toxic in older patients.

Keywords: Cetuximab; Comorbidity; Elderly; Quality of life; Survival; Toxicity.

MeSH terms

  • Age Factors
  • Aged
  • Alanine / administration & dosage
  • Alanine / analogs & derivatives
  • Antineoplastic Combined Chemotherapy Protocols / administration & dosage
  • Antineoplastic Combined Chemotherapy Protocols / adverse effects
  • Cetuximab / administration & dosage*
  • Cetuximab / adverse effects
  • Clinical Trials, Phase III as Topic
  • Colorectal Neoplasms / drug therapy*
  • Colorectal Neoplasms / genetics
  • Colorectal Neoplasms / pathology
  • Disease-Free Survival
  • Female
  • Humans
  • Male
  • Molecular Targeted Therapy*
  • Neoplasm Metastasis
  • Proto-Oncogene Proteins p21(ras) / genetics
  • Quality of Life*
  • Randomized Controlled Trials as Topic
  • Retrospective Studies
  • Survival Rate
  • Triazines / administration & dosage

Substances

  • KRAS protein, human
  • Triazines
  • brivanib
  • Proto-Oncogene Proteins p21(ras)
  • Alanine
  • Cetuximab