First-Line Cetuximab Monotherapy in KRAS/NRAS/BRAF Mutation-Negative Colorectal Cancer Patients

Clinical Drug Investigation
Vladimir M MoiseyenkoEvgeny N Imyanitov

Abstract

Colorectal carcinomas (CRCs) are sensitive to treatment by anti-epidermal growth factor receptor (EGFR) antibodies only if they do not carry activating mutations in down-stream EGFR targets (KRAS/NRAS/BRAF). Most clinical trials for chemo-naive CRC patients involved combination of targeted agents and chemotherapy, while single-agent cetuximab or panitumumab studies included either heavily pretreated patients or subjects who were not selected on the basis of molecular tests. We hypothesized that anti-EGFR therapy would have significant efficacy in chemo-naive patients with KRAS/NRAS/BRAF mutation-negative CRC. Nineteen patients were prospectively included in the study. Two (11%) patients experienced partial response (PR) and 11 (58%) subjects showed stable disease (SD). Median time to progression approached 6.1 months (range 1.6-15.0 months). Cetuximab efficacy did not correlate with RNA expression of EGFR and insulin-like growth factor 2 (IGF2). Only one tumor carried PIK3CA mutation, and this CRC responded to cetuximab. Exome analysis of patients with progressive disease (PD) revealed 1 CRC with high-level microsatellite instability and 1 instance of HER2 oncogene amplification; 3 of 4 remaining patients with PD had allergic r...Continue Reading

References

Jan 29, 2005·Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology·Ki Young ChungLeonard B Saltz
Dec 13, 2007·Annals of Oncology : Official Journal of the European Society for Medical Oncology·A PessinoA Sobrero
Sep 17, 2008·Clinical Colorectal Cancer·Usman Shah, Richard M Goldberg
Mar 17, 2009·Japanese Journal of Clinical Oncology·Kei MuroDaisuke Asahi
Mar 25, 2010·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·J Randolph HechtJordan Berlin
Mar 26, 2011·International Journal of Clinical Oncology·Ayako MizotaKei Muro
Nov 20, 2013·Clinical Oncology : a Journal of the Royal College of Radiologists·I E G van HellemondR H T Koornstra
Feb 28, 2014·World Journal of Gastroenterology : WJG·Alexander Stein, Carsten Bokemeyer
Sep 6, 2014·Annals of Oncology : Official Journal of the European Society for Medical Oncology·E Van CutsemUNKNOWN ESMO Guidelines Working Group
Sep 24, 2014·Neoplasia : an International Journal for Oncology Research·Giampietro GaspariniAntonio Marchetti
Feb 13, 2015·European Journal of Cancer : Official Journal for European Organization for Research and Treatment of Cancer (EORTC) [and] European Association for Cancer Research (EACR)·Filippo PietrantonioSandro Barni
May 16, 2015·Cancer Metastasis Reviews·Stefan Zimmermann, Solange Peters
Jun 2, 2015·The New England Journal of Medicine·Dung T LeLuis A Diaz
Jun 20, 2015·Critical Reviews in Oncology/hematology·Filippo PietrantonioRoberto Iacovelli
Feb 3, 2016·Drug Resistance Updates : Reviews and Commentaries in Antimicrobial and Anticancer Chemotherapy·Edith A Perez
Feb 6, 2016·Advances in Anatomic Pathology·Raju K PillaiScott D Patterson
Apr 12, 2016·International Journal of Urology : Official Journal of the Japanese Urological Association·Masaki Shiota, Masatoshi Eto

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Citations

Jun 10, 2020·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Marloes ZoetemelkPatrycja Nowak-Sliwinska

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