National University Cancer Institute, Singapore, Singapore
Yu Yang Soon , Martin R. Stockler , Lisa Askie , Michael J. Boyer
Background: We previously published a meta-analysis which identified a survival benefit with extended duration of chemotherapy in patients with advanced non-small cell lung cancer. We have updated our meta-analysis with results from new or updated randomized trials presented in June 2008 to Oct 2013. Methods: Biomedical literature databases and conference proceedings were searched for randomized controlled trials (RCTs) comparing: (i) a defined number of cycles versus continuation of the same chemotherapy until disease progression; (ii) a defined number of cycles versus a larger defined number of cycles of identical chemotherapy, and (iii) a defined number of cycles of identical initial chemotherapy versus the addition of cycles of alternative chemotherapy. Meta-analysis was performed using the fixed effect model. The primary outcome was overall survival (OS) and secondary outcomes included progression-free survival (PFS), adverse events (AE), and health-related quality of life (HRQL). Results: We identified updated results of two trials from the previous meta-analysis and found four new trials, resulting in a total of 17 trials including 5069 patients. Extending chemotherapy improved PFS substantially (hazard ratio [HR], 0.70; 95% CI 0.66 to 0.75; P < 0.00001, I2 = 72%, Chi2 P < 0.0001) and OS modestly (HR, 0.91, 95% CI 0.85 to 0.96, P = 0.001, I2=14%, Chi2 P = 0.29). Subgroup analysis revealed that the effects on PFS were greater for trials extending chemotherapy with third generation chemotherapy regimens, non-platinum regimens and maintenance therapy trial design. There was no evidence of difference in the effects on overall survival between subgroups defined by use of third generation chemotherapy regimens or platinum regimens and trial design. Extending chemotherapy was associated with more frequent AE in all trials where it was reported and impaired HRQL in two of 12 trials. Conclusions: This updated meta-analysis continues to demonstrate improvement in both progression- free and overall survival benefit with extended duration of chemotherapy in patients with advanced non-small cell lung carcinoma.
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