title: Bayesian network meta-comparison of maintenance treatments for stage IIIb/IV non-small-cell lung cancer (NSCLC) patients with good performance status not progressing after first-line induction chemotherapy: results by performance status, EGFR mutation, histology and response to previous induction.
abstract: BACKGROUND
  Recent trials have suggested that maintenance treatments improve outcomes for patients not progressing after first-line therapy for advanced non-small-cell lung cancer (NSCLC). However, physicians have little guidance on selecting which patients benefit the most and what drug or regimen is optimal. Here, we report a systematic review and network meta-analysis of maintenance treatments in subgroups determined by performance status (PS), epidermal growth factor receptor (EGFR) mutation, histology and response to induction.
  
  
  METHODS
  PubMed and conference proceedings were reviewed and individual study relative efficacy measures were meta-analysed in a Bayesian hierarchical model. The primary outcome, overall survival (OS), was evaluated in terms of (i) posterior surface under cumulative ranking curve (SUCRA), (ii) probability of being best treatment, (iii) probability of outperforming no maintenance, and (iv) posterior median hazard ratio (95% credible interval). Secondary outcomes were progression-free survival (PFS) and adverse events.
  
  
  RESULTS
  Twelve trials evaluating eight maintenance treatments in 3850 patients were meta-analysed. Selected maintenance treatments showed clinically meaningful benefits of ⩾20% reduction in hazards of death with ⩾90% probability of outperforming no maintenance in terms of OS: (i) switch to or continue pemetrexed (nonsquamous), continue gemcitabine, or switch to EGFR tyrosine kinase inhibitors (TKIs) for PS 0 patients, (ii) switch to pemetrexed (nonsquamous) for PS 1 patients, (iii) switch to EGFR TKI for EGFR mutation positive patients, (iv) switch to or continue pemetrexed or switch to EGFR TKI for nonsquamous patients, (v) continue gemcitabine for squamous patients, (vi) switch to docetaxel or continue gemcitabine for responders to induction, or (vii) switch to or continue pemetrexed (nonsquamous) or switch to EGFR TKI for patients with stable disease post-induction.
  
  
  CONCLUSIONS
  Maintenance treatments show clinically meaningful survival benefits in good performance status patients with advanced NSCLC not progressing after first-line chemotherapy. Benefits are optimised by targeting specific maintenance to individual patients guided by PS, EGFR mutation status, histology and response to induction.
authors.affiliation: Health Services and Systems Research, Duke-NUS Graduate Medical School, Singapore.
authors.forename: Pui San
authors.initials: PS
authors.lastname: Tan
authors.affiliation: Hospital do Coração Cancer Center (HCor Onco), and Research Institute, Brazil; Centro Paulista de Oncologia, Brazil; Oncoclinicas do Brasil, Brazil; Johns Hopkins University, Baltimore, MD, USA.
authors.forename: Gilberto
authors.initials: G
authors.lastname: Lopes
authors.affiliation: Centre for Quantitative Medicine, Office of Clinical Sciences, Duke-NUS Graduate Medical School, Singapore.
authors.forename: Sanchalika
authors.initials: S
authors.lastname: Acharyya
authors.affiliation: Health Services and Systems Research, Duke-NUS Graduate Medical School, Singapore.
authors.forename: Marcel
authors.initials: M
authors.lastname: Bilger
authors.affiliation: Centre for Quantitative Medicine, Office of Clinical Sciences, Duke-NUS Graduate Medical School, Singapore; H. Milton Stewart School of Industrial and Systems Engineering, Georgia Institute of Technology, USA. Electronic address: ben.haaland@isye.gatech.edu.
authors.forename: Benjamin
authors.initials: B
authors.lastname: Haaland
mesh_terms: D000970:Antineoplastic Agents / Q000009:adverse effects / Q000627:therapeutic use*; D001499:Bayes Theorem; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy* / Q000235:genetics / Q000401:mortality / Q000473:pathology; D003841:Deoxycytidine / Q000031:analogs & derivatives / Q000627:therapeutic use; D018450:Disease Progression; D018572:Disease-Free Survival; D000077143:Docetaxel; D057915:Drug Substitution; D066246:ErbB Receptors / Q000037:antagonists & inhibitors / Q000235:genetics*; D020022:Genetic Predisposition to Disease; D006801:Humans; D060828:Induction Chemotherapy / Q000009:adverse effects / Q000401:mortality; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000401:mortality / Q000473:pathology; D060046:Maintenance Chemotherapy / Q000009:adverse effects / Q000401:mortality; D008390:Markov Chains; D009010:Monte Carlo Method; D009154:Mutation; D009367:Neoplasm Staging; D000068437:Pemetrexed / Q000627:therapeutic use; D010641:Phenotype; D047428:Protein Kinase Inhibitors / Q000627:therapeutic use; D012307:Risk Factors; D016019:Survival Analysis; D043823:Taxoids / Q000627:therapeutic use; D013997:Time Factors; D016896:Treatment Outcome; D000093542:Gemcitabine
chemical_list: D000970:Antineoplastic Agents; D047428:Protein Kinase Inhibitors; D043823:Taxoids; D000068437:Pemetrexed; D003841:Deoxycytidine; D000077143:Docetaxel; C512478:EGFR protein, human; D066246:ErbB Receptors; D000093542:Gemcitabine
keywords: Advanced non-small-cell lung cancer (NSCLC); Bayesian network meta-analysis; Maintenance