title: First-line anti-EGFR monoclonal antibodies in panRAS wild-type metastatic colorectal cancer: A systematic review and meta-analysis.
abstract: BACKGROUND
  The use of anti-EGFR monoclonal antibodies (MoAbs) is restricted in Europe to RAS wild-type metastatic colorectal cancer (mCRC) patients. While up today these targeted agents have been mainly chosen as salvage treatment in later lines, their use in first-line in combination with chemotherapy is highly debated.
  
  
  METHODS
  MEDLINE/PubMed, Cochrane Library, ASCO University, ESMO/ECCO conferences were searched for randomized controlled trials (RCTs) comparing first-line anti-EGFR MoAbs cetuximab or panitumumab plus chemotherapy to chemotherapy alone or with bevacizumab in patients with RAS wild-type colorectal cancer. Data extraction was conducted according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement.
  
  
  RESULTS
  Seven eligible RCTs were identified. In the overall RAS wild-type population (N=2719), anti-EGFR MoAbs significantly improved OS (HR=0.81; 95%CI, 0.71-0.92; p=0.002), PFS (HR=0.77; 95%CI, 0.60-0.98; p=0.03) and objective response rate (ORR) (RR=1.33; 95%CI, 1.09-1.62; p=0.004). The addition of an anti-EGFR MoAb to chemotherapy alone improved PFS (p<0.001) and ORR (p<0.001) with a trend toward longer OS (p=0.07). As compared to bevacizumab, anti-EGFR MoAbs significantly improved OS (HR=0.80; 95%CI, 0.69-0.92; p=0.003), but not PFS (HR=0.94; 95%CI, 0.74-1.19; p=0.59) or ORR (RR=1.10; 95%CI, 0.97-1.25; p=0.12). No significant differences were found with respect to the chemotherapy backbone (oxaliplatin- versus irinotecan-based).
  
  
  CONCLUSIONS
  The choice of an anti-EGFR MoAb as first-line biologic is a valid option in RAS wild-type patients candidate to a doublet with infusional 5-FU. While attempting to further refine molecular selection, clinical considerations are crucial in planning the treatment strategy.
authors.affiliation: Fondazione IRCCS Istituto Nazionale dei Tumori, Medical Oncology Unit, Milan, Italy. Electronic address: filippo.pietrantonio@istitutotumori.mi.it.
authors.forename: Filippo
authors.initials: F
authors.lastname: Pietrantonio
authors.affiliation: Polo Oncologico, Azienda Ospedaliero-Universitaria Pisana, Pisa, Italy.
authors.forename: Chiara
authors.initials: C
authors.lastname: Cremolini
authors.affiliation: Azienda Ospedaliera Treviglio, Unità Operativa Oncologia, Treviglio, Bergamo, Italy.
authors.forename: Fausto
authors.initials: F
authors.lastname: Petrelli
authors.affiliation: Fondazione IRCCS Istituto Nazionale dei Tumori, Medical Oncology Unit, Milan, Italy.
authors.forename: Maria
authors.initials: M
authors.lastname: Di Bartolomeo
authors.affiliation: Polo Oncologico, Azienda Ospedaliero-Universitaria Pisana, Pisa, Italy.
authors.forename: Fotios
authors.initials: F
authors.lastname: Loupakis
authors.affiliation: Fondazione IRCCS Istituto Nazionale dei Tumori, Medical Oncology Unit, Milan, Italy.
authors.forename: Claudia
authors.initials: C
authors.lastname: Maggi
authors.affiliation: Polo Oncologico, Azienda Ospedaliero-Universitaria Pisana, Pisa, Italy.
authors.forename: Carlotta
authors.initials: C
authors.lastname: Antoniotti
authors.affiliation: Fondazione IRCCS Istituto Nazionale dei Tumori, Medical Oncology Unit, Milan, Italy.
authors.forename: Filippo
authors.initials: F
authors.lastname: de Braud
authors.affiliation: Polo Oncologico, Azienda Ospedaliero-Universitaria Pisana, Pisa, Italy.
authors.forename: Alfredo
authors.initials: A
authors.lastname: Falcone
authors.affiliation: Fondazione IRCCS Istituto Nazionale dei Tumori, Medical Oncology Unit, Milan, Italy; Department of Radiology, Oncology and Human-Pathology, Sapienza University of Rome, Rome, Italy.
authors.forename: Roberto
authors.initials: R
authors.lastname: Iacovelli
mesh_terms: D000911:Antibodies, Monoclonal / Q000627:therapeutic use*; D000068258:Bevacizumab / Q000627:therapeutic use; D015179:Colorectal Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000401:mortality / Q000473:pathology; D066246:ErbB Receptors / Q000037:antagonists & inhibitors*; D011905:Genes, ras; D006801:Humans; D009362:Neoplasm Metastasis
chemical_list: D000911:Antibodies, Monoclonal; D000068258:Bevacizumab; D066246:ErbB Receptors
keywords: Bevacizumab; Cetuximab; Colorectal cancer; Overall survival; Panitumumab; Randomized clinical trials