title: Single agent panitumumab in KRAS wild-type metastatic colorectal cancer patients following cetuximab-based regimens: Clinical outcome and biomarkers of efficacy.
abstract: BACKGROUND
  Few data are available outlining outcomes of panitumumab in advanced colorectal cancer patients benefiting from prior cetuximab-based regimens.
  
  
  METHODS
  Thirty patients with KRAS wild type metastatic colorectal cancer with clinical benefit from prior cetuximab-based regimens between May 2004 and October 2011 were reviewed at nine Italian Institutions. Inclusion key criteria included interruption of cetuximab for reasons other than progressive disease. Patients were classified according to prior regimens (0 or ≥1), prior response or stabilization, surgery of metastases, and Köhne prognostic score. At the time of subsequent progression, patients were treated with single agent panitumumab until progressive disease, unacceptable toxicity, or consent withdrawal.
  
  
  RESULTS
  Panitumumab obtained 67% disease control rate and 30% objective response rate, with median PFS of 4.2 and median OS of 9.6 mo. Patients with BRAF/NRAS/PI3KCA and KRAS (by mutant enriched technique) wild-type tumors had the best chance of response to panitumumab.
  
  
  CONCLUSIONS
  Single agent panitumumab provided significant clinical benefit in heavily pretreated patients without acquired resistance to prior cetuximab-based regimens.
authors.affiliation: Medical Oncology Department; Fondazione I.R.C.C.S. Istituto Nazionale Tumori; Milan, Italy.
authors.forename: Filippo
authors.initials: F
authors.lastname: Pietrantonio
authors.affiliation: Department of Pathology; Fondazione I.R.C.C.S. Istituto Nazionale Tumori; Milan, Italy.
authors.forename: Federica
authors.initials: F
authors.lastname: Perrone
authors.affiliation: Medical Oncology Department; Fondazione I.R.C.C.S. Istituto Nazionale Tumori; Milan, Italy.
authors.forename: Pamela
authors.initials: P
authors.lastname: Biondani
authors.affiliation: Medical Oncology Department; Fondazione I.R.C.C.S. Istituto Nazionale Tumori; Milan, Italy.
authors.forename: Claudia
authors.initials: C
authors.lastname: Maggi
authors.affiliation: Department of Pathology; Fondazione I.R.C.C.S. Istituto Nazionale Tumori; Milan, Italy.
authors.forename: Andrea
authors.initials: A
authors.lastname: Lampis
authors.affiliation: Department of Pathology; Fondazione I.R.C.C.S. Istituto Nazionale Tumori; Milan, Italy.
authors.forename: Claudia
authors.initials: C
authors.lastname: Bertan
authors.affiliation: Medical Oncology Unit; Ospedale Niguarda Ca' Granda; Milan, Italy.
authors.forename: Filippo
authors.initials: F
authors.lastname: Venturini
authors.affiliation: Oncology Department; Azienda Ospedaliera Universitaria Integrata di Verona; Borgo Trento Hospital; Verona, Italy.
authors.forename: Luca
authors.initials: L
authors.lastname: Tondulli
authors.affiliation: Medical Oncology Unit; A.O. San Paolo; Milan, Italy.
authors.forename: Daris
authors.initials: D
authors.lastname: Ferrari
authors.affiliation: Department of Oncology; Istituto Scientifico San Raffaele; Milan, Italy.
authors.forename: Vincenzo
authors.initials: V
authors.lastname: Ricci
authors.affiliation: Medical Oncology Unit; Az Ospedale S. Gerardo; Monza, Italy.
authors.forename: Federica
authors.initials: F
authors.lastname: Villa
authors.affiliation: Medical Oncology Unit; Policlinico San Marco; Zingonia (Bergamo), Italy.
authors.forename: Gloria
authors.initials: G
authors.lastname: Barone
authors.affiliation: Medical Oncology Unit; IDO Policlinico; Monza, Italy.
authors.forename: Nadia
authors.initials: N
authors.lastname: Bianco
authors.affiliation: Casa di Cura Igea; Milan, Italy.
authors.forename: Antonio
authors.initials: A
authors.lastname: Ghidini
authors.affiliation: Medical Oncology Department; Fondazione I.R.C.C.S. Istituto Nazionale Tumori; Milan, Italy.
authors.forename: Ilaria
authors.initials: I
authors.lastname: Bossi
authors.affiliation: Medical Oncology Department; Fondazione I.R.C.C.S. Istituto Nazionale Tumori; Milan, Italy.
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Fanetti
authors.affiliation: Medical Oncology Department; Fondazione I.R.C.C.S. Istituto Nazionale Tumori; Milan, Italy.
authors.forename: Maria
authors.initials: M
authors.lastname: Di Bartolomeo
authors.affiliation: Medical Oncology Department; Fondazione I.R.C.C.S. Istituto Nazionale Tumori; Milan, Italy.
authors.forename: Filippo
authors.initials: F
authors.lastname: de Braud
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000911:Antibodies, Monoclonal / Q000627:therapeutic use*; D061067:Antibodies, Monoclonal, Humanized / Q000627:therapeutic use*; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D000068818:Cetuximab; D015179:Colorectal Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009362:Neoplasm Metastasis; D000077544:Panitumumab; D011518:Proto-Oncogene Proteins / Q000235:genetics*; D016283:Proto-Oncogene Proteins p21(ras); D018631:ras Proteins / Q000235:genetics*
chemical_list: D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D000970:Antineoplastic Agents; C117307:KRAS protein, human; D011518:Proto-Oncogene Proteins; D000077544:Panitumumab; D016283:Proto-Oncogene Proteins p21(ras); D018631:ras Proteins; D000068818:Cetuximab
keywords: KRAS; cetuximab; colorectal cancer; panitumumab; rechallenge
references.citation: J Clin Oncol. 2008 Dec 10;26(35):5705-12
references.pmid: 19001320
references.citation: J Clin Oncol. 2004 Apr 1;22(7):1201-8
references.pmid: 14993230
references.citation: Neuro Oncol. 2009 Dec;11(6):725-36
references.pmid: 19246520
references.citation: Oncologist. 2012;17(1):14
references.pmid: 22210091
references.citation: Cancer. 2011 Oct 15;117(20):4623-32
references.pmid: 21456008
references.citation: Clin Cancer Res. 2011 Jul 15;17(14):4901-14
references.pmid: 21632860
references.citation: J Clin Oncol. 2007 May 1;25(13):1658-64
references.pmid: 17470858
references.citation: N Engl J Med. 2009 Apr 2;360(14):1408-17
references.pmid: 19339720
references.citation: Nature. 2012 Jun 28;486(7404):532-6
references.pmid: 22722830
references.citation: JAMA. 2010 Oct 27;304(16):1812-20
references.pmid: 20978259
references.citation: Ann Oncol. 2009 Jan;20(1):84-90
references.pmid: 18669866
references.citation: J Clin Oncol. 2013 Feb 20;31(6):759-65
references.pmid: 23182985
references.citation: Eur J Cancer. 2009 Jan;45(2):228-47
references.pmid: 19097774
references.citation: Ann Oncol. 2002 Feb;13(2):308-17
references.pmid: 11886010
references.citation: Lancet Oncol. 2010 Aug;11(8):753-62
references.pmid: 20619739
references.citation: N Engl J Med. 2008 Oct 23;359(17):1757-65
references.pmid: 18946061
references.citation: N Engl J Med. 2007 Nov 15;357(20):2040-8
references.pmid: 18003960
references.citation: Biochim Biophys Acta. 2008 Feb;1780(2):75-88
references.pmid: 18047841
references.citation: Ann Oncol. 2011 Jul;22(7):1535-1546
references.pmid: 21228335
references.citation: Nat Med. 2012 Jan 22;18(2):221-3
references.pmid: 22270724
references.citation: Clin Colorectal Cancer. 2010 Dec;9(5):315-8
references.pmid: 21208847
references.citation: Cancer Chemother Pharmacol. 2009 May;63(6):1017-22
references.pmid: 18781300
references.citation: Eur J Cancer. 2012 Jul;48(10):1466-75
references.pmid: 22446022
references.citation: Ann Oncol. 2012 Sep;23(9):2313-2318
references.pmid: 22396447
references.citation: J Clin Oncol. 2010 Nov 1;28(31):4697-705
references.pmid: 20921465