Chemotherapy and biologic use in the routine management of metastatic colorectal cancer in Australia: is clinical practice following the evidence?

Intern Med J. 2019 Apr;49(4):446-454. doi: 10.1111/imj.14115.

Abstract

Background: Emerging evidence on the optimal use of chemotherapy and biologics in patients with metastatic colorectal cancer should impact management in routine care. Recent studies have demonstrated benefits for initial triplet chemotherapy (5-fluorouracil, oxaliplatin and irinotecan, FOLFOXIRI) and for initial treatment with an epidermal growth factor receptor inhibitor (EGFRi) in patients with a RAS wild-type tumour and a left-sided primary tumour.

Aim: To explore evolving pattern of metastatic colorectal cancer care over time in Australia.

Methods: We analysed data from the Treatment of Recurrent and Advanced Colorectal Cancer registry.

Results: From July 2009 to December 2017, 2552 metastatic colorectal cancer patients were entered into the Treatment of Recurrent and Advanced Colorectal Cancer registry. Of 1585 patients who initially underwent chemotherapy, treatment was with a doublet in 76%. FOLFOXIRI was given to 22 patients (1.4%), mostly young patients and those with potentially resectable disease. Along with first-line chemotherapy, 61% received bevacizumab, while 3.3% received an EGFRi, predominantly over the last 2 years. Within the KRAS wild-type left-sided tumour cohort, EGFRi use increased from 9% in 2015 to 37% in 2017. Across treatment sites, there was a wide variation in the utilisation of FOLFOXIRI and EGFRi therapy; bevacizumab use was more consistent. A clear impact on survival outcomes from these regimens is not evident, potentially due to multiple confounders.

Conclusion: Doublet chemotherapy + bevacizumab remains the dominant initial strategy, with limited uptake of triplet chemotherapy and of EGFRi. Potential explanations include uncertainty about the significance of post hoc analyses for EGFRi and concerns regarding adverse events for both strategies.

Keywords: bevacizumab; cetuximab; metastatic colorectal cancer; panitumumab; real-world outcomes.

Publication types

  • Multicenter Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Aged, 80 and over
  • Angiogenesis Inhibitors / therapeutic use
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use*
  • Australia / epidemiology
  • Bevacizumab / therapeutic use*
  • Biological Products / therapeutic use*
  • Colorectal Neoplasms / drug therapy*
  • Disease-Free Survival
  • Female
  • Fluorouracil / therapeutic use
  • Humans
  • Leucovorin / therapeutic use
  • Male
  • Middle Aged
  • Neoplasm Metastasis
  • Organoplatinum Compounds / therapeutic use
  • Registries
  • Treatment Outcome
  • Young Adult

Substances

  • Angiogenesis Inhibitors
  • Biological Products
  • Organoplatinum Compounds
  • Bevacizumab
  • Leucovorin
  • Fluorouracil