title: The impact of clinical characteristics on outcomes from maintenance therapy in non-small cell lung cancer: A systematic review with meta-analysis.
abstract: OBJECTIVE
  Although maintenance therapy has been a routine treatment paradigm for advanced non-small cell lung cancer (NSCLC), there is currently lack of direct evidence to identify patients most likely to benefit from maintenance therapy for advanced NSCLC.
  
  
  METHODS
  Trials comparing maintenance therapy with placebo or observation in NSCLC were identified. The primary endpoint was overall survival (OS) in trial population and predefined subgroups. Other endpoints included progression-free survival (PFS) in trial population and predefined subgroups, toxicities and health-related quality of life (QoL).
  
  
  RESULTS
  13 trials with 4960 patients were identified. Maintenance therapy yielded a statistically significant but clinically modest improvement in OS (hazard ratio [HR], 0.84; 95% confidence interval [CI], 0.78-0.89, P<0.001), without significant difference between switch and continuation strategy (HR, 0.83 vs. 0.86; Pinteraction=0.631). Patients with performance status (PS) of 0 derived more PFS benefit (HR, 0.52; 95% CI, 0.45-0.61) than those with PS of 1 (HR, 0.69; 95% CI, 0.63-0.76; Pinteraction=0.002). Patients with adenocarcinoma derived more PFS benefit (HR, 0.54; 95% CI, 0.46-0.64) than those with squamous cell carcinoma (HR, 0.85; 95% CI, 0.68-1.06; Pinteraction=0.001). Patients with activating epidermal growth factor receptor (EGFR) mutations derived more survival benefit than those with wild-type EGFR tumors in terms of OS (HR, 0.53 vs. 0.85, Pinteraction=0.086) and PFS (HR, 0.20 vs. 0.80, Pinteraction=0.003). Response to first-line therapy did not significantly predict additional benefit from maintenance therapy. Toxicities occurred more frequently in patients treated with maintenance therapy but health-related QoL was not adversely affected by maintenance therapy.
  
  
  CONCLUSIONS
  Maintenance therapy with either a continuation or a switch strategy yields a statistically significant but clinically modest improvement in OS for patients with advanced NSCLC. Factors that may predict benefit from maintenance therapy (tumor histology, PS, or EGFR mutation status), as well as economic considerations should be taken into account before initiating maintenance therapy.
authors.affiliation: Department of Medical Oncology, Shanghai Pulmonary Hospital, Tongji University School of Medicine, No. 507, Zhengmin Road, Shanghai 200433, China.
authors.forename: Fei
authors.initials: F
authors.lastname: Zhou
authors.affiliation: Department of Medical Oncology, Shanghai Pulmonary Hospital, Tongji University School of Medicine, No. 507, Zhengmin Road, Shanghai 200433, China.
authors.forename: Tao
authors.initials: T
authors.lastname: Jiang
authors.affiliation: Department of Emergency, Tongji Hospital Affiliated to Tongji University, No. 389, Xincun Road, Shanghai 200065, China.
authors.forename: Wanrong
authors.initials: W
authors.lastname: Ma
authors.affiliation: Department of Medical Oncology, Shanghai Pulmonary Hospital, Tongji University School of Medicine, No. 507, Zhengmin Road, Shanghai 200433, China.
authors.forename: Guanghui
authors.initials: G
authors.lastname: Gao
authors.affiliation: Department of Medical Oncology, Shanghai Pulmonary Hospital, Tongji University School of Medicine, No. 507, Zhengmin Road, Shanghai 200433, China.
authors.forename: Xiaoxia
authors.initials: X
authors.lastname: Chen
authors.affiliation: Department of Medical Oncology, Shanghai Pulmonary Hospital, Tongji University School of Medicine, No. 507, Zhengmin Road, Shanghai 200433, China. Electronic address: caicunzhoudr@163.com.
authors.forename: Caicun
authors.initials: C
authors.lastname: Zhou
mesh_terms: D002289:Carcinoma, Non-Small-Cell Lung / Q000401:mortality* / Q000473:pathology / Q000628:therapy*; D002986:Clinical Trials as Topic; D003131:Combined Modality Therapy / Q000009:adverse effects / Q000379:methods; D005260:Female; D006801:Humans; D008175:Lung Neoplasms / Q000401:mortality* / Q000473:pathology / Q000628:therapy*; D008297:Male; D009367:Neoplasm Staging; D011788:Quality of Life; D016019:Survival Analysis; D016896:Treatment Outcome
keywords: Maintenance therapy; Meta-analysis; Non-small cell lung cancer; Systematic review