Assessing the relative effectiveness and tolerability of treatments in small cell lung cancer: a network meta-analysis

Background: The combination of Cisplatin plus Etoposide (EP) is currently the standard treatment for small cell lung cancer (SCLC). However, a large number of alternative treatments (monotherapies and combinations) have been studied in randomized controlled trials (RCTs) to identify more effective treatments. Aim of the present study was to assess the relative effectiveness and tolerability of these treatments.

Methods: PubMed, EMBASE and Cochrane Central Register of Controlled Trials were systematically searched to identify all RCTs that compared treatments for SCLC. Then, effectiveness of the treatments relative to the combination of Cisplatin plus Etoposide, reference treatment) was estimated by performing a network of treatments analysis. The analysis evaluated two efficacy outcomes (complete response - CR and objective response rate - ORR) and two tolerability outcomes (neutropenia and febrile neutropenia). All RCTs that provided data for calculating the odds ratios (OR) for the selected outcomes were considered. The network analysis involved direct and indirect analyses.

Results: We identified 71 articles eligible for inclusion, involving 91 different treatments. In total, 16,026 patients were included in the analysis. In the direct analysis the combination of Cisplatin plus Cyclophosphamide plus Etoposide plus Epirubicin showed better response than EP for the ORR outcome, but with worse tolerability (presence of neutropenia). The indirect analysis revealed that the combination of Cisplatin plus Doxorubicin plus Etoposide (plus Vincrisitine) showed better response that EP for the ORR outcome.

Conclusions: No therapy shows better response for the two efficacy outcomes (CR and ORR); though, Cisplatin plus Doxorubicin plus Etoposide plus Vincrisitine might be a promising therapy for SCLC. The results should be interpreted with caution because the network was dominated by indirect comparisons. Large scale head-to-head RCTs are needed to confirm the present findings.