Comparative Efficacy and Safety of Different Regimens of Advanced Gastrointestinal Stromal Tumors After Failure Prior Tyrosine Kinase Inhibitors: A Network Meta-Analysis.

INTRODUCTION

The prospect of targeted therapies for advanced gastrointestinal stromal tumors (GISTs) has been dramatically transformed after encouraging results achieved in recent clinical trials. At present, the number of second- and third-line treatments are increasing, although the challenge is to take into account the differences between these interventions. Therefore, our goal is to evaluate the investigation of different regimens currently used in GISTs based on findings from phase II or phase III randomized controlled trials (RCTs), and then indirectly compare the effectiveness and safety of the available therapies.

METHODS

The qualified literatures in relevant sources were searched systematically. Studies to identify RCTs of which main endpoints were progression-free survival (PFS), overall survival (OS), and grade 3 or more adverse events (AEs) in patients with GISTs were considered for inclusion.

RESULTS

Eight RCTs met our inclusion criteria, which involved 2351 patients. For PFS, compared with placebo, imatinib, and sunitinib, regorafenib (HR = 0.12, 95% CI 0.07-0.23; HR = 0.27, 95% CI 0.19-0.39; HR = 0.36, 95% CI 0.19-0.72, respectively) and ripretinib (HR = 0.15, 95% CI 0.09-0.25; HR = 0.33, 95% CI 0.16-0.68; HR = 0.44, 95% CI 0.25-0.78, respectively) were significantly correlated with the improvement of PFS, and regorafenib may be the preferred option according to the analysis of treatment rankings. For OS, compared with placebo, imatinib, and sunitinib, masitinib (HR = 0.13, 95% CI 0.04-0.44; HR = 0.13, 95% CI 0.04-0.51; HR = 0.27, 95%CI 0.09-0.84) and ripretinib (HR = 0.36, 95% CI 0.21-0.62; HR = 0.36, 95% CI 0.16-0.80; HR = 0.18, 95% CI 0.09-0.36, respectively) were significantly more effective, and masitinib may be the best choice according to treatment ranking analysis. Statistically, regorafenib can be considered to be the highest in high-grade AEs, while the rate of severe AEs of ripretinib and masitinib was likely the lowest.

CONCLUSION

Our results show that ripretinib has the most favorable balance between effectiveness and tolerability among the different treatment regimens for GISTs.