Multi-agent chemotherapy in advanced soft tissue sarcoma (STS) ; A systematic review and meta-analysis
A partir d'une revue systématique des essais cliniques publiés entre 1974 et 2016 et incluant 5 044 patients atteints d'un sarcome des tissus mous de stade avancé, cette méta-analyse compare l'efficacité, du point de vue de la survie globale et de la survie sans progression, d'une chimiothérapie combinant plusieurs agents et d'une chimiothérapie à base d'un seul agent
Background : Despite a lack of improvement in overall survival (OS) with doxorubicin-based combinations over doxorubicin alone in advanced STS, the role of multi-agent chemotherapy remains poorly defined. Methods : We conducted a systematic review and meta-analysis to evaluate benefits and harms of multi-agent chemotherapy in advanced STS. Eligible studies were randomized trials of chemotherapy in advanced STS comparing single agent to multi-agent therapy. Data from studies reporting a hazard ratio (HR) and 95% confidence intervals (CI) for OS and progression-free survival (PFS) were pooled in a meta-analysis. Meta-regression was utilized to explore the association between efficacy (OS and PFS) and both toxicity and dose intensity. Results : We identified 22 trials published between 1974 and April 2016 and comprising 5044 patients. Overall, multi-agent chemotherapy was associated with improved OS (HR:0.79, p=0.02), and borderline improvement in PFS (HR:0.86, p=0.05). While the effect on OS was similar in trials with non-anthracycline controls compared to those with anthracycline controls (HR for OS 0.73 vs. 0.82, p for difference=0.63) there was a non-significantly greater effect for multi-agent chemotherapy on PFS in non-anthracycline RCT (HR for PFS 0.73 vs. 0.91, p for difference=0.13). Compared to studies with cytotoxic therapy-based multi-agent therapy, a non-significantly greater magnitude of effect among studies with biological/cytostatic experimental groups was seen (HR for OS 0.64 vs. 0.86, p for difference=0.37). There was a borderline significant association between dose reductions (which were more common in combination arms) and worse PFS (beta=0.70, p=0.053). Conclusion : Multi-agent chemotherapy is associated with a modest, but statistically significant improvement in outcomes in STS. Combining chemotherapy with non-cytotoxic agents might represent a promising strategy.