title: KRAS as prognostic biomarker in metastatic colorectal cancer patients treated with bevacizumab: a pooled analysis of 12 published trials.
abstract: The significance of KRAS in advanced colorectal cancer (CRC) treated with bevacizumab (B) is not well understood. We conducted a systematic review and pooled analysis of published trials with the aim to assess the predictive and prognostic role of KRAS status in patients treated with B. We performed a systematic search of PubMed, EMBASE, Web of Science, and Cochrane Register of Controlled Trials. The primary endpoints included objective response rate (RR), progression-free survival (PFS), and overall survival (OS). The odds ratio (OR) for RR and hazard ratios (HRs) were calculated or extracted by published data either using a fixed effect model or a random effect model. A total of 12 studies were included. A total of 2,266 patients were analysed (54 % were KRAS wt). The pooled RRs for KRAS wild-type (wt) versus mutated (mut) patients were 54.8 and 48.3 %, respectively (OR 1.42, P = 0.02). Median PFS was significantly longer in KRAS wt patients compared with that in KRAS mut patients (HR = 0.85; 95 % confidence interval (CI) 0.74-0.98; P = 0.02). Similarly, median OS was significantly better in wt KRAS patients compared with that in mut KRAS patients (HR = 0.65; 95 % CI 0.46-0.92; P = 0.01). This pooled analysis of 12 published studies shows that KRAS wt status is a good prognostic factor for B-based chemotherapy. Also, KRAS wt CRC is associated with a better RR with B plus chemotherapy than mut counterpart.
authors.affiliation: Medical Oncology Unit, Oncology Department, Azienda Ospedaliera Treviglio, Piazzale Ospedale 1, 24047 Treviglio (BG), Italy. faupe@libero.it
authors.forename: Fausto
authors.initials: F
authors.lastname: Petrelli
authors.forename: Andrea
authors.initials: A
authors.lastname: Coinu
authors.forename: Mary
authors.initials: M
authors.lastname: Cabiddu
authors.forename: Mara
authors.initials: M
authors.lastname: Ghilardi
authors.forename: Sandro
authors.initials: S
authors.lastname: Barni
mesh_terms: D020533:Angiogenesis Inhibitors / Q000627:therapeutic use*; D061067:Antibodies, Monoclonal, Humanized / Q000627:therapeutic use*; D000068258:Bevacizumab; D014408:Biomarkers, Tumor / Q000235:genetics*; D002986:Clinical Trials as Topic; D015179:Colorectal Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology*; D018572:Disease-Free Survival; D006801:Humans; D015201:Meta-Analysis as Topic; D009154:Mutation / Q000235:genetics; D011379:Prognosis; D011518:Proto-Oncogene Proteins / Q000235:genetics*; D016283:Proto-Oncogene Proteins p21(ras); D018631:ras Proteins / Q000235:genetics*
chemical_list: D020533:Angiogenesis Inhibitors; D061067:Antibodies, Monoclonal, Humanized; D014408:Biomarkers, Tumor; C117307:KRAS protein, human; D011518:Proto-Oncogene Proteins; D000068258:Bevacizumab; D016283:Proto-Oncogene Proteins p21(ras); D018631:ras Proteins