(P 34) RIPRETINIB IN COMBINATION WITH OTHER TKIS IN CHINESE PATIENTS WITH ADVANCED GASTROINTESTINAL STROMAL TUMOR: A MULTI-CENTER RETROSPECTIVE ANALYSIS

Objective: Although targeted therapies have significantly improved the prognosis for patients with Gastrointestinal stromal tumors (GISTs), resistance to these treatments remains a major challenge. Combining tyrosine kinase inhibitors (TKIs) with other targeted agents may help overcome this resistance in GISTs. When selecting a combination regimen, it is crucial to consider the efficacy and safety of the chosen drug. Ripretinib, a novel switch-control TKI, has demonstrated promising antitumor activity and safety properties in both 2nd and 4th-line treatments of advanced GIST. This is possible to make ripretinib as a preferred backbone in a combination regimen. A previous case report suggested that ripretinib combined with other TKIs could provide clinical benefits for patients with advanced GIST who progressed after ripretinib treatment. This retrospective analysis aims to further evaluate the effectiveness and tolerability of ripretinib plus other TKIs in patients with advanced GIST from multiple centers.

Methods: Patients diagnosed with GIST, who received ripretinib and sequentially combined it with other TKIs between March 2021 and March 2023, were retrospectively analyzed. Clinicopathological characteristics, treatment regimens, and follow-up visit information were collected. Clinical outcomes, including objective response rate (ORR), progression-free survival (PFS), overall survival, and safety, were assessed.

Results: A total of 10 patients were enrolled, with a median age of 56 years (range, 45-60); 7 (70%) of these patients were female. The data cutoff date was April 20, 2023. The median PFS1 for ripretinib 150 mg QD was 6.8 months (95% CI: 6.05-NA). As the disease progressed, six patients underwent treatment with a combination of Ripretinib and Sunitinib, whereas four patients received Ripretinib in combined with either Regorafenib or Imatinib, with 2 patients for each respective combination (Table 1). Overall, the median PFS2 for combination therapy was 4.7 months (95% CI: 3.15-NA). The best responses to ripretinib combined with other TKIs were PR (10%, 1/10) and SD (60%, 6/10). After a median follow-up of 18.0 months (range: 16.13-NA), the total mPFS and mOS on ripretinib were 13.63 months (95% CI: 9.53-NA) and 18.0 months (95% CI: 17.77-NA), respectively. During the combination therapy period, six patients reported treatment-emergent adverse events (TEAEs), all of which were grade 1/2. The most common TEAEs were palmar-plantar erythrodysesthesia syndrome (30%), diarrhea (20%), and fatigue (20%). A summary of TEAEs is provided in Table 2. No patients experienced serious adverse events (SAEs).

Conclusion: This retrospective study demonstrated meaningful clinical benefits of combining Ripretinib with available TKIs in treating patients with advanced GIST. The safety profile of the combined therapy was considered acceptable. Further research is necessary to establish the optimal dosing regimen for these two targeted drugs and to clarify their mode of action.