Factors predicting benefit from maintenance therapy in advanced non-small cell lung cancer: a systematic review and meta-analysis

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Year
Authors
Liu J1, Lai M2
1SKH Memorial Hospital, Taiwan
2Graduate Institute of Epidemiology and Preventive Medicine, College of Public Health, National Taiwan University, Taiwan
Abstract
Background: Previous meta-analyses have shown that maintenance therapy (MT) improves survival in patients with advanced non-small cell lung cancer (NSCLC). However, whether MT could improve overall survival is still unknown.

Objectives: To conduct a systematic review and meta-analysis of the efficacy of MT with either a continuous or a switch strategy for patients with advanced NSCLC.

Methods: We performed a literature search of online databases (MEDLINE, CENTRAL, and Scopus) and a manual search of relevant conference proceedings (ASCO, and ESMO). Trial registries were searched for ongoing and unpublished studies. Randomized controlled trials that reported the effect of MT on survival or progression-free survival in histologically or cytologically proven stage IIIB or IV NSCLC patients were included. Two reviewers independently evaluated the eligibility of the trials, extracted the data, and assessed risk for bias of the included studies. The primary outcome was overall survival (OS), and secondary outcomes included progression-free survival (PFS). Subgroup analyses were conducted by histological subtype, epidermal growth factor receptor (EGFR) mutation status, and response to induction therapy.

Results: Fifteen trials involving 6396 participants with advanced NSCLC were included in this meta-analysis. Pooled results showed MT substantially improved OS (hazard ratio (HR) 0.85; 95% (confidence interval (CI) 0.80 to 0.91; I2 = 0%) and PFS (HR 0.63; 95% CI 0.56 to 0.72; I2 = 69%). Statistically significant improvement of both OS and PFS was observed in switch MT (HR 0.85; 95% CI 0.78 to 0.92; I2 = 0%) and continuous strategy (HR 0.86; 95% CI 0.76 to 0.97; I2 = 0%). Combination of two maintenance agents is superior to single agent in terms of PFS (HR 0.72; 95% CI 0.59 to 0.88; I2 = 69%), but not OS. Subgorup meta-analysis revealed that maintenance therapy yielded improved PFS for patients with adenocarcinoma (HR 0.52; 95% CI 0.43 to 0.63; I2 = 63%) than for non-adenocarcinoma (HR 0.73; 95% CI 0.62 to 0.86; interaction P = 0.008).

Conclusions: MT for patients with advanced NSCLC significantly increases OS and PFS, irrespective of treatment strategy.