Outcomes of North American, Japanese, and European extensive-disease small cell lung cancer (ED-SCLC) patients under irinotecan-platinum or etoposide-platinum therapy: Systematic review and meta-analysis.

Abstract

e18534 Background: Superiority of irinotecan-platinum (IP) regimens over etoposide-platinum (EP) in ED-SCLC has been extensively debated, with ethnic and pharmacogenomics issues hypothesized as causes of the divergent findings. We undertook a systematic review to scrutinize the data according to geographic origin. Methods: Randomized controlled trials comparing first-line EP doublets versus IP in ED-SCLC patients were searched in major meeting proceedings and databases. The outcomes were overall survival (OS), one-year survival, two-year survival, and safety. Meta-analyses were performed using random-effects model. Subgroup analyses and meta-regression were undertaken to compare and measure the impact of geographical origin of study over the estimated effect size. Results: Seven studies (2,029 patients) were included. IP improved OS worldwide (HR = 0.83; 95% CI 0.76-0.92; P>0.001; I²=0%). However, the impact of IP on OS was different according to geographic origin, with relevant benefit for Japanese, little benefit for North American/Australian and intermediate for European patients (P for interaction = 0.029, table 1). One year survival was homogenously improved from 34% with EP to 40% with IP (P=0.006). IP improved two year survival just for Japanese and European patients but not to North American ones (Table). Toxicity was not impacted by trial origin. Conclusions: IP improved survival for both Western and Eastern patients, but seems to exist a gradient of benefit according to geographic origins, with maximal benefit for Japanese, some relevant for European ones and little, if any, for North American/Australian patients. These findings should be taken in account when considering IP or EP as first-line therapy for ED-SCLC patients worldwide. [Table: see text]