Affordable Access

deepdyve-link
Publisher Website

Frequency of S492R mutations in the epidermal growth factor receptor: analysis of plasma DNA from patients with metastatic colorectal cancer treated with panitumumab or cetuximab monotherapy

Authors
  • Price, Timothy1
  • Ang, Agnes2
  • Boedigheimer, Michael2
  • Kim, Tae Won3
  • Li, Jin4
  • Cascinu, Stefano5
  • Ruff, Paul6
  • Satya Suresh, Attili7
  • Thomas, Anne8
  • Tjulandin, Sergei9
  • Peeters, Marc10
  • 1 Clinical Oncology Research and Haematology and Medical Oncology Service Departments, The Queen Elizabeth Hospital and University of Adelaide, Woodville, Australia;
  • 2 Amgen Inc, USA
  • 3 Asan Medical Center, University of Ulsan College of Medicine, South Korea
  • 4 Tongji University East Hospital, China , (China)
  • 5 Universita Politecnica delle Marche, Italy , (Italy)
  • 6 University of Witwatersrand, South Africa , (South Africa)
  • 7 Apollo Hospital, India , (India)
  • 8 University of Leicester, UK
  • 9 N. N. Blokhin Cancer Research Center of RAMS, Russia
  • 10 Antwerp University Hospital, Belgium , (Belgium)
Type
Published Article
Journal
Cancer Biology & Therapy
Publisher
Landes Bioscience
Publication Date
Oct 07, 2020
Volume
21
Issue
10
Pages
891–898
Identifiers
DOI: 10.1080/15384047.2020.1798695
PMID: 33026965
PMCID: PMC7583702
Source
PubMed Central
Keywords
Disciplines
  • Research Paper
License
Unknown

Abstract

Background Antibodies against epidermal growth factor receptor (EGFR), panitumumab, a fully human monoclonal antibody, and cetuximab, a human/mouse chimeric monoclonal antibody, have shown clinical efficacy in metastatic colorectal cancer (mCRC). In the phase 3 noninferiority ASPECCT (ClinicalTrials.gov, NCT01001377) study, panitumumab was demonstrated to be noninferior to cetuximab and provided a similar overall survival benefit for patients with chemotherapy-refractory wild-type KRAS exon 2 mCRC. However, some patients eventually develop resistance to anti-EGFR therapy. EGFR p.S492R mutation was previously identified as conferring resistance to cetuximab, but not to panitumumab. Methods This biomarker study analyzed plasma samples from ASPECCT collected at both baseline and posttreatment. Results No EGFR p.S492R mutations were identified at baseline; however, after treatment the EGFR p.S492R mutation was detected in 1% of patients treated with panitumumab versus 16% of those treated with cetuximab, supporting that, in a large population, this mutation is more likely to be induced by cetuximab than by panitumumab. There were, however, no significant differences in progression-free survival or overall survival between patients who were wild-type compared with those with the S492R mutation within the cetuximab arm or the overall population. Conclusions These results may support targeting treatment to small patient subgroups based on the presence of emerging EGFR mutations and provide a molecular rationale for rechallenging with a different anti-EGFR agent in patients who develop resistance. Prospective studies are needed to evaluate the efficacy of panitumumab in the EGFR p.S492R mutant population.

Report this publication

Statistics

Seen <100 times