Panitumumab-based maintenance after oxaliplatin discontinuation in metastatic colorectal cancer: A retrospective analysis of two randomised trials

Int J Cancer. 2019 Jul 15;145(2):576-585. doi: 10.1002/ijc.32110. Epub 2019 Jan 24.

Abstract

Panitumumab is approved for RAS wild-type metastatic colorectal cancer and was evaluated in Phase III (PRIME, NCT00364013) and Phase II (PEAK, NCT00819780) first-line randomised studies. This retrospective analysis of these trials investigated efficacy and toxicity of panitumumab-based maintenance after oxaliplatin discontinuation in RAS wild-type patients. First-line regimens were FOLFOX4 ± panitumumab in PRIME and mFOLFOX6 plus panitumumab or mFOLFOX6 plus bevacizumab in PEAK. Outcomes included median progression-free survival (PFS) and overall survival (OS), from randomisation and oxaliplatin discontinuation, and toxicity. Overall, median duration of panitumumab plus 5-fluorouracil/leucovorin (5-FU/LV) maintenance was 21 (interquartile range: 11-41) weeks; that of 5-FU/LV ± bevacizumab maintenance was 16 (6-31) weeks. Median OS from randomisation was 40.2 (95% confidence interval: 30.3-50.4) and 39.1 (34.2-63.0) months for panitumumab plus 5-FU/LV maintenance and 24.1 (17.7-33.0) and 28.9 (21.0-32.0) months for 5-FU/LV ± bevacizumab maintenance in PRIME and PEAK, respectively. Median PFS from randomisation was 16.6 (11.3-23.6) and 15.4 (11.6-18.4) months for panitumumab plus 5-FU/LV maintenance and 12.6 (9.4-16.2) and 13.1 (9.5-16.6) months for 5-FU/LV ± bevacizumab maintenance in PRIME and PEAK, respectively. From oxaliplatin discontinuation, median OS was 33.9 (24.7-42.8) and 33.5 (24.5-54.9) months for panitumumab plus 5-FU/LV maintenance and 16.4 (12.4-24.1) and 23.3 (15.7-26.3) months for 5-FU/LV ± bevacizumab maintenance in PRIME and PEAK, respectively; PFS was 11.7 (7.8-19.2) and 9.7 (5.8-14.8) months and 7.1 (5.6-10.2) and 7.0 (3.9-10.6) months, respectively. The most frequently reported adverse events were rash, fatigue and diarrhoea. Maintenance of panitumumab plus 5-FU/LV after oxaliplatin discontinuation was well tolerated and may be an acceptable treatment paradigm for patients demonstrating a good response to first-line treatment. Prospective studies are warranted.

Keywords: epidermal growth factor receptor; maintenance; metastatic colorectal cancer; panitumumab; survival; toxicity.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Antineoplastic Combined Chemotherapy Protocols / administration & dosage*
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use
  • Bevacizumab / administration & dosage*
  • Bevacizumab / therapeutic use
  • Clinical Trials, Phase II as Topic
  • Clinical Trials, Phase III as Topic
  • Colorectal Neoplasms / drug therapy*
  • Female
  • Fluorouracil / administration & dosage
  • Fluorouracil / therapeutic use
  • Humans
  • Leucovorin / administration & dosage
  • Leucovorin / therapeutic use
  • Maintenance Chemotherapy
  • Male
  • Middle Aged
  • Neoplasm Metastasis / drug therapy*
  • Organoplatinum Compounds / administration & dosage
  • Organoplatinum Compounds / therapeutic use
  • Oxaliplatin / administration & dosage
  • Oxaliplatin / therapeutic use
  • Panitumumab / administration & dosage*
  • Panitumumab / therapeutic use
  • Randomized Controlled Trials as Topic
  • Retrospective Studies
  • Survival Analysis
  • Treatment Outcome

Substances

  • Organoplatinum Compounds
  • Oxaliplatin
  • Bevacizumab
  • Panitumumab
  • Leucovorin
  • Fluorouracil

Supplementary concepts

  • Folfox protocol

Associated data

  • ClinicalTrials.gov/NCT00364013
  • ClinicalTrials.gov/NCT00819780