Evaluating the efficacy of tyrosine kinase inhibitors and other targeted therapies in imatinib-resistant gastrointestinal stromal tumors: A comprehensive Bayesian network meta-analysis.

Abstract

e16475 Background: Gastrointestinal stromal tumors (GISTs) are the most common mesenchymal tumors of the gastrointestinal tract, primarily driven by KIT or PDGFRA mutations. Imatinib has transformed GIST treatment; however, resistance typically emerges within 20–24 months, necessitating effective second-line therapies such as sunitinib, regorafenib, ripretinib, and masitinib. Methods: A Bayesian network meta-analysis of 17 studies including 2,422 patients evaluated the efficacy of tyrosine kinase inhibitors (TKIs) and other targeted therapies for progression-free survival (PFS), overall survival (OS), and objective response rate (ORR) in imatinib-resistant GIST. Mean differences (MDs) and relative risks (RRs) with 95% credible intervals (CrIs) were calculated, and treatments were ranked using Surface Under the Cumulative Ranking Curve (SUCRA) values. Control was used as the reference in all comparisons. Results: For PFS, masitinib showed the most significant improvement (MD: 11.78 months, 95% CrI: 0.29–23.49; SUCRA: 86.52%), followed by regorafenib (MD: 9.33 months, 95% CrI: 4.15–14.88; SUCRA: 79.7%) and sunitinib (MD: 8.68 months, 95% CrI: 3.47–14.13; SUCRA: 74.71%). In OS, masitinib ranked highest (MD: 34.09 months, 95% CrI: -20.64 to 90.13; SUCRA: 83.56%), followed by regorafenib (MD: 27.35 months, 95% CrI: -35.13 to 90.22; SUCRA: 76.96%) and sunitinib (MD: 17.16 months, 95% CrI: -9.66 to 44.89; SUCRA: 69.96%). Regorafenib led in ORR (RR: 8.23, 95% CrI: 0.68–97.04; SUCRA: 76.36%), followed by ripretinib (RR: 5.53, 95% CrI: 0.42–104.01; SUCRA: 63.91%) and sunitinib (RR: 4.56, 95% CrI: 0.66–40.67; SUCRA: 58.12%). Conclusions: Masitinib and regorafenib demonstrate the most promising efficacy for improving survival and treatment response in imatinib-resistant GIST patients. These findings emphasize the importance of tailored therapeutic strategies for advanced GIST management. Outcome Treatment Mean Difference / Relative Risk (95% CrI) SUCRA (%) Progression-Free Survival (PFS) (Months) Control Reference 26.00 Masitinib 11.78 (0.29 to 23.49) 86.52 Regorafenib 9.33 (4.15 to 14.88) 79.70 Sunitinib 8.68 (3.47 to 14.13) 74.71 Ripretinib 7.72 (0.04 to 15.50) 68.65 Sorafenib 3.10 (-8.19 to 13.73) 44.13 Pimitespib 2.33 (-7.75 to 12.46) 40.13 Overall Survival (OS) (Months) Control Reference 38.51 Masitinib 34.09 (-20.64 to 90.13) 83.56 Regorafenib 27.35 (-35.13 to 90.22) 76.96 Sunitinib 17.16 (-9.66 to 44.89) 69.96 Ripretinib 6.65 (-35.54 to 49.47) 50.83 Objective Response Rate (Relative Risk) Control Reference 15.94 Regorafenib 8.23 (0.68 to 97.04) 76.36 Ripretinib 5.53 (0.42 to 104.01) 63.91 Sunitinib 4.56 (0.66 to 40.67) 58.12 Sorafenib 4.95 (0.07 to 311.89) 57.53