title: Vemurafenib and panitumumab combination tailored therapy in BRAF-mutated metastatic colorectal cancer: a case report.
abstract: As the knowledge on cancer genetic alterations progresses, it fosters the need for more personalized therapeutic intervention in modern cancer management. Recently, mutations in KRAS, BRAF, and PIK3CA genes have emerged as important mechanisms of resistance to EGFR-targeted therapy in metastatic colorectal cancer (mCRC). Here we report the first case of a mCRC patient whose disease had progressed on standard lines of treatment and for which we devised a personalized therapeutic approach consisting of vemurafenib (Zelboraf) and panitumumab (Vectibix), based on the following molecular profile: BRAF(V600E)-mutant, amplified EGFR (double positive) and WT KRAS, WT PIK3CA, not-amplified HER2 (triple negative). This new combination therapy was well tolerated and resulted in a strong control of the disease. In particular, the vemurafenib-panitumumab combination appears to limit the typical toxicity of single agents, since no cutaneous toxic effects typically associated with vemurafenib were observed. Here we report the first clinical evidence that the combination of an anti-EGFR (panitumumab) and an inhibitor of BRAF(V600E) (vemurafenib) is well tolerated and results in a strong disease control in an extensively pretreated mCRC patient.
authors.affiliation: Department of Molecular Medicine; Sapienza University of Rome; Rome, Italy; Medical Oncology; IDI IRCCS; Rome, Italy.
authors.forename: Carlo
authors.initials: C
authors.lastname: Capalbo
authors.affiliation: Medical Oncology; IDI IRCCS; Rome, Italy; Department of Clinical and Molecular Medicine; Sapienza University of Rome; Rome, Italy.
authors.forename: Paolo
authors.initials: P
authors.lastname: Marchetti
authors.affiliation: Department of Experimental Medicine; Sapienza University of Rome; Rome, Italy.
authors.forename: Anna
authors.initials: A
authors.lastname: Coppa
authors.affiliation: Department of Medical-Surgical Sciences and Biotechnologies; Sapienza University of Rome; Rome, Italy.
authors.forename: Antonella
authors.initials: A
authors.lastname: Calogero
authors.affiliation: Department of Molecular Medicine; Sapienza University of Rome; Rome, Italy.
authors.forename: Emanuela
authors.initials: E
authors.lastname: Anastasi
authors.affiliation: Department of Molecular Medicine; Sapienza University of Rome; Rome, Italy.
authors.forename: Amelia
authors.initials: A
authors.lastname: Buffone
authors.affiliation: Department of Molecular Medicine; Sapienza University of Rome; Rome, Italy.
authors.forename: Francesca
authors.initials: F
authors.lastname: Belardinilli
authors.affiliation: Department of Anatomical, Histological, Forensic Medicine and Orthopedic Science; Forensic Medicine Section; Sapienza University of Rome; Rome, Italy.
authors.forename: Matteo
authors.initials: M
authors.lastname: Gulino
authors.affiliation: Department of Anatomical, Histological, Forensic Medicine and Orthopedic Science; Forensic Medicine Section; Sapienza University of Rome; Rome, Italy; Neuromed IRCCS; Pozzilli, Italy.
authors.forename: Paola
authors.initials: P
authors.lastname: Frati
authors.affiliation: Department of Radiological, Oncological and Pathological Sciences; Sapienza University of Rome; Rome, Italy.
authors.forename: Carlo
authors.initials: C
authors.lastname: Catalano
authors.affiliation: Department of Radiological, Oncological and Pathological Sciences; Sapienza University of Rome; Rome, Italy.
authors.forename: Enrico
authors.initials: E
authors.lastname: Cortesi
authors.affiliation: Department of Molecular Medicine; Sapienza University of Rome; Rome, Italy.
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Giannini
authors.affiliation: Neuromed IRCCS; Pozzilli, Italy; Department of Molecular Medicine; Center for Life Nanoscience@Sapienza; Italian Institute of Technology and Istituto Pasteur; Fondazione Cenci-Bolognetti; Sapienza University of Rome; Rome, Italy.
authors.forename: Alberto
authors.initials: A
authors.lastname: Gulino
mesh_terms: D000230:Adenocarcinoma / Q000188:drug therapy* / Q000235:genetics / Q000556:secondary; D000911:Antibodies, Monoclonal / Q000008:administration & dosage; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D015179:Colorectal Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology; D006801:Humans; D007211:Indoles / Q000008:administration & dosage; D008297:Male; D008875:Middle Aged; D009154:Mutation; D000077544:Panitumumab; D048493:Proto-Oncogene Proteins B-raf / Q000235:genetics*; D013449:Sulfonamides / Q000008:administration & dosage; D000077484:Vemurafenib
chemical_list: D000911:Antibodies, Monoclonal; D007211:Indoles; D013449:Sulfonamides; D000077484:Vemurafenib; D000077544:Panitumumab; C482119:BRAF protein, human; D048493:Proto-Oncogene Proteins B-raf
keywords: BRAF; EGFR; colorectal cancer; cutaneous toxicity; panitumumab; personalized medicine; target therapy; vemurafenib
references.citation: N Engl J Med. 2012 Feb 23;366(8):707-14
references.pmid: 22356324
references.citation: N Engl J Med. 2010 Aug 26;363(9):809-19
references.pmid: 20818844
references.citation: J Clin Oncol. 2010 Mar 1;28(7):1254-61
references.pmid: 20100961
references.citation: Cancer Biol Ther. 2013 Aug;14(8):703-10
references.pmid: 23792568
references.citation: Therap Adv Gastroenterol. 2013 Sep;6(5):381-95
references.pmid: 24003339
references.citation: Nat Med. 2013 Nov;19(11):1389-400
references.pmid: 24202392
references.citation: Cancer Cell. 2011 Jan 18;19(1):11-5
references.pmid: 21251612
references.citation: Nature. 2010 Mar 18;464(7287):427-30
references.pmid: 20179705
references.citation: Nat Med. 2013 May;19(5):619-25
references.pmid: 23584089
references.citation: Nature. 2013 Feb 14;494(7436):251-5
references.pmid: 23302800
references.citation: Cancer Discov. 2013 Jul;3(7):742-50
references.pmid: 23614898
references.citation: Ecancermedicalscience. 2014 Jan 16;8:387
references.pmid: 24482672
references.citation: J Clin Oncol. 2009 Dec 10;27(35):5931-7
references.pmid: 19884549
references.citation: N Engl J Med. 2013 Sep 12;369(11):1023-34
references.pmid: 24024839
references.citation: J Hematol Oncol. 2013 Apr 25;6:30
references.pmid: 23617957
references.citation: Expert Rev Anticancer Ther. 2013 May;13(5):597-611
references.pmid: 23617351
references.citation: Oncologist. 2011;16(8):1061-8
references.pmid: 21737577
references.citation: Nature. 2010 Dec 16;468(7326):973-7
references.pmid: 21107323
references.citation: Nature. 2012 Jan 26;483(7387):100-3
references.pmid: 22281684
references.citation: Curr Oncol Rep. 2013 Jun;15(3):249-59
references.pmid: 23463215
references.citation: N Engl J Med. 2011 Jun 30;364(26):2507-16
references.pmid: 21639808
references.citation: Med J Aust. 2013 Oct 7;199(7):471-3
references.pmid: 24099207
references.citation: Cancer Res. 2012 Feb 1;72(3):779-89
references.pmid: 22180495
references.citation: Cancer Res. 2012 Feb 15;72(4):969-78
references.pmid: 22205714
references.citation: Cancer Cell. 2012 Nov 13;22(5):668-82
references.pmid: 23153539
references.citation: Cancer Discov. 2012 Mar;2(3):227-35
references.pmid: 22448344
references.citation: Cancer Cell. 2010 Dec 14;18(6):683-95
references.pmid: 21156289
references.citation: N Engl J Med. 2004 Jul 22;351(4):337-45
references.pmid: 15269313
references.citation: Clin Cancer Res. 2013 Feb 1;19(3):657-67
references.pmid: 23251002
references.citation: Nat Med. 2013 Nov;19(11):1401-9
references.pmid: 24202393