(P 42) THE EFFICACY AND SAFETY OF RIPRETINIB IN THE TREATMENT OF CHINESE PATIENTS WITH ADVANCED GASTROINTESTINAL STROMAL TUMORS (GISTS): A SINGLE-INSTITUTION ANALYSIS

Objective: Ripretinib, a broad-spectrum KIT and PDGFRA switch-control TKI (Smith et al., 2019), is approved for the fourth-line and above (≥4L) therapy for GISTs. Ripretinib demonstrated comparable overall efficacy and favorable safety versus sunitinib as 2L therapy in INTRIGUE (Bauer S, et al., 2022) and was superior to sunitinib for Chinese patients harboring KIT exon 11 mutations (Li J, et al., 2023), and was recommended as a 2L treatment option by NCCN and CSCO GIST guidelines. Here, we report a clinical practice data evaluating the efficacy and safety of ripretinib in Chinese patients with advanced GISTs.

Methods: Between November 1, 2020 and November 1, 2022, patients with recurrent or metastatic GISTs treated with ripretinib receiving at least one tumor assessment in Tianjin Medical University Cancer Institute & Hospital were prospectively reviewed. The study endpoints were median progression-free survival (mPFS), median overall survival (mOS), objective response rate (ORR), disease control rate (DCR) and safety. Factors associated with the efficacy of ripretinib were aslo analyzed by product limit method (KM).

Results: A total of 23 patients were included in this study. With a median follow-up time of 12.2 months, the mPFS was 11.0 months (95% CI: 8.5, NA) and mOS was 27.0 months (95% CI: 11.0, NA). 3 patients achieved PR and 18 patients achieved SD, and the ORR and DCR were 13% and 91%, respectively. For patients with KIT exon 11 mutations, the mPFS was 12.0 months (95% CI: 8.5, NA) and mOS was 27.0 months (95% CI: 12.9, NA). Compared with clinical trials, the use of ripretinib was more complex in real world. 3 patients discontinued ripretinib due to financial reasons, and 2 patients underwent surgery after 4 and 5 months with ripretinib respectively and discontinued ripretinib after surgery. Although the recommended dose of ripretinib was 150 mg QD, 8/9 patients (one dose reduction) were treated with 100 mg QD for economic reasons. The mOS of patients received 100 mg QD vs 150 mg QD were 11.0 months (95% CI: 6.9, NA) vs 27.0 months (95% CI: 12.9, NA) (P = 0.15, trending in Difference). The starting lines of ripretinib also had an impact on survival data. The mPFS of ripretinib as 2L and 3L therapies vs ≥4L therapy were 14.0 months vs 8.5 months (P < 0.05) and the mOS were not reached vs 11.0 months (P = 0.07, trending in Difference). Other analyses showed that duration of therapy（DOT）of imatinib did not seem to affect the survival data of ripretinib, while DOT of sunitinib seemed to have a trend to affect OS and DOT of regorafenib affected both the PFS and OS of ripretinib. Ripretinib was associated with a favorable safety profile and was also generally well tolerated. After disease progression, 6 patients received ripretinib Intra-patient dose escalation and 4 of the 6 patients achieved SD. 3 patients received combination therapy of ripretinib with other TKIs and 2 of the 3 patients achieved SD. The safety profile for ripretinib dose escalation or combination with other TKIs was acceptable.

Conclusion: Ripretinib has significant clinical benefit and good safety in Chinese patients with advanced GISTs. Earlier use of ripretinib may benefit the survival of the patients as well as for Chinese patients harboring exon 11 mutations. Dose escalation or combination of ripretinib with other TKIs after disease progression may provide additional clinically meaningful benefit with an acceptable safety profile. Further prospective clinical studies with larger sample sizes are needed.