(P 38) EFFICACY AND SAFETY OF RIPRETINIB IN THE TREATMENT OF ADVANCED GASTROINTESTINAL STROMAL TUMORS: A MULTICENTER RETROSPECTIVE STUDY

Objective: Ripretinib is a switch-control tyrosine kinase inhibitor (TKI) that broadly inhibits KIT and PDGFRA mutations including the multiple primary and secondary mutations that drive disease progression and drug resistance in GIST. In the INVICTUS phase 3 study (NCT03353753) and the bridging phase 2 study conducted in China (NCT04282980), ripretinib demonstrated a statistically significant improvement in median progression-free survival and overall survival with an acceptable safety profile in patients with ≥4th-line GIST. Ripretinib was approved for ≥4th-line therapy of advanced GIST in China in March 2021. However, due to its expensive price, there are limited clinical applications and research reports in China. This retrospective study aims to investigate the efficacy and safety of ripretinib among Chinese patients.

Methods: Clinical data of advanced GIST patients treated with Ripretinib from three hospitals in Hubei Province from April 2021 to January 2023 were retrospectively collected, including lines of treatment lines, efficacy, drug discontinuation and safety profile. The efficacy was determined by overall survival (OS) and cancer specific survival (CSS). Safety was assessed by the incidence and severity of adverse events (AEs).

Results: A total of 29 patients were enrolled, of which 19 were male (65.5%) and 10 were female (34.5%); the median age at the time of ripretinib administration was 60 (28~85) years. Ripretinib was used as a fourth-line treatment in 15 cases (51.7%), third-line treatment in 11 cases (37.9%), and second-line treatment in 3 cases (10.4%). In the first evaluation after ripretinib treatment in 29 patients, partial response (PR) was observed in 5 cases, stable disease (SD) in 16 cases, and progressive disease (PD) in 8 cases. The objective response rate (ORR) was 17.2%, and the disease control rate (DCR) was 72.4%. Adverse events were observed in 25 patients (86.2%), including grade 1-2 adverse events in 23 cases (79.3%) and grade 3 adverse events in 2 cases (6.9%). By the last follow-up, 14 out of 29 patients had died. The 1-year OS rate was 56.4%, and the 1-year CSS rate was 62.1% for the entire group of patients. 11 patients discontinued ripretinib treatment, with 1 patient due to gastrointestinal bleeding and 10 patients due to financial reasons, among which 4 cases experienced disease progression, and the doctor recommended increasing the dose of ripretinib, but the patients chose to discontinue ripretinib due to economical burden. Compared to patients who discontinued ripretinib, those who continued treatment had a significantly longer 1-year OS rate (69.6% vs. 36.4%, P＜0.01) and 1-year CSS rate (80.4% vs. 36.4%, P＜0.01)

Conclusion: Ripretinib can effectively control the disease progression of advanced GIST in patients who have failed first-line or multiple-line treatments, with mild adverse events and good tolerability. Compared to patients who discontinued ripretinib, those who continued treatment had more significant survival benefits. Financial reasons were the main factors leading to treatment discontinuation. The inclusion of ripretinib in national reimbursement drug list may bring substantial benefits to patients with advanced GIST.