title: Is ovarian cancer a targetable disease? A systematic review and meta-analysis and genomic data investigation.
abstract: OBJECTIVE
  The current gold-standard for the first-line treatment in IIIb/IV stages of epithelial ovarian cancer (EOC) is the combination of carboplatin and paclitaxel plus bevacizumab in some countries. In the era of personalized medicine, there is still uncertainty on the impact of several molecularly targeted agents, which have been investigated for the management of this disease. To shed light on the actual role of targeted therapy in EOC, a systematic review and meta-analysis was performed.
  
  
  METHODS
  Clinical trials were selected by searching "Pubmed" database and abstracts from major cancer meetings within the time-frame of January 2004-June 2015. The endpoints were survival outcome and response rate (RR). Hazard ratios (HRs) of survival outcomes, with confidence intervals and odds-ratios (ORs) of RR, were extracted from retrieved studies and used for current analysis. Meta-analysis was carried out by random effect model.
  
  
  RESULTS
  30 randomized trials for a total of 10,530 patients were selected and included in the final analysis. A benefit in terms of OS (pooled HR 0.915; 95%CI 0.840-0.997; p=0.043), particularly for anti-angiogenetic agents (HR 0.872; 95%CI 0.761-1.000; p=0.049), has been demonstrated for targeted therapy. Moreover, a significant advantage in platinum-resistant subgroup in term of PFS (HR 0.755; 95%CI 0.624-0.912; p=0.004) was found.
  
  
  CONCLUSIONS
  This systematic review and meta-analysis provide the first evidence that targeted therapy is potentially able to translate into improved survival of EOC patients, with a major role played by anti-angiogenetic drugs. The role of target therapy is underlined in the platinum-resistant setting that represents the "pain in the neck" in EOC management.
authors.affiliation: Department of Experimental and Clinical Medicine, Magna Græcia University, Catanzaro, Italy.
authors.forename: Nicoletta
authors.initials: N
authors.lastname: Staropoli
authors.affiliation: Department of Experimental and Clinical Medicine, Magna Græcia University, Catanzaro, Italy.
authors.forename: Domenico
authors.initials: D
authors.lastname: Ciliberto
authors.affiliation: Department of Experimental and Clinical Medicine, Magna Græcia University, Catanzaro, Italy.
authors.forename: Silvia
authors.initials: S
authors.lastname: Chiellino
authors.affiliation: Department of Experimental and Clinical Medicine, Magna Græcia University, Catanzaro, Italy.
authors.forename: Francesca
authors.initials: F
authors.lastname: Caglioti
authors.affiliation: Department of Experimental and Clinical Medicine, Magna Græcia University, Catanzaro, Italy.
authors.forename: Teresa Del
authors.initials: TD
authors.lastname: Giudice
authors.affiliation: Department of Experimental and Clinical Medicine, Magna Græcia University, Catanzaro, Italy.
authors.forename: Simona
authors.initials: S
authors.lastname: Gualtieri
authors.affiliation: Department of Experimental and Clinical Medicine, Magna Græcia University, Catanzaro, Italy.
authors.forename: Angela
authors.initials: A
authors.lastname: Salvino
authors.affiliation: Department of Experimental and Clinical Medicine, Magna Græcia University, Catanzaro, Italy.
authors.forename: Alessandra
authors.initials: A
authors.lastname: Strangio
authors.affiliation: Department of Experimental and Clinical Medicine, Magna Græcia University, Catanzaro, Italy.
authors.forename: Cirino
authors.initials: C
authors.lastname: Botta
authors.affiliation: Department of Gynecologic and Urologic Oncology, Fondazione Pascale, National Cancer Institute of Naples, Naples, Italy.
authors.forename: Sandro
authors.initials: S
authors.lastname: Pignata
authors.affiliation: Department of Experimental and Clinical Medicine, Magna Græcia University, Catanzaro, Italy.
authors.forename: Pierfrancesco
authors.initials: P
authors.lastname: Tassone
authors.affiliation: Department of Experimental and Clinical Medicine, Magna Græcia University, Catanzaro, Italy.
authors.forename: Pierosandro
authors.initials: P
authors.lastname: Tagliaferri
mesh_terms: D020533:Angiogenesis Inhibitors / Q000627:therapeutic use*; D014408:Biomarkers, Tumor / Q000235:genetics / Q000378:metabolism*; D018450:Disease Progression; D018572:Disease-Free Survival; D019008:Drug Resistance, Neoplasm; D005260:Female; D006801:Humans; D058990:Molecular Targeted Therapy / Q000379:methods*; D016017:Odds Ratio; D010051:Ovarian Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism / Q000401:mortality; D018579:Patient Selection; D057285:Precision Medicine; D012307:Risk Factors; D015398:Signal Transduction / Q000187:drug effects; D013997:Time Factors; D016896:Treatment Outcome
chemical_list: D020533:Angiogenesis Inhibitors; D014408:Biomarkers, Tumor
keywords: meta-analysis; ovarian cancer; systematic review; systemic chemotherapy; targeted therapy