(P 44) RIPRETINIB FOR THE TREATMENT OF CHINESE PATIENTS WITH ADVANCED GASTROINTESTINAL STROMAL TUMORS HARBORING KIT SECONDARY MUTATIONS: A MULTICENTER, RETROSPECTIVE STUDY

Objective: Secondary KIT mutations in patients with gastrointestinal stromal tumors (GISTs) are the primary cause of resistance to tyrosine kinase inhibitors (TKIs), and mutational heterogeneity increases with successive lines of therapy. Approximately 70% and 77% of patients develop secondary resistance to first-line imatinib or at least three lines of treatment. Previous studies indicated that the presence of secondary mutations is associated with reduced median progression-free survival (PFS) in patients receiving sunitinib as second-line (7 vs 19 months) and regorafenib as third-line treatment (approximately 120 vs 170 days). In view of ripretinib is ability to inhibit many common primary and secondary KIT mutations, this study aims to assess the efficacy and safety of ripretinib in Chinese patients with advanced GIST harboring secondary mutations.

Methods: Patients with advanced GIST harboring primary and secondary KIT mutations who received ripretinib 150mg once daily following progression on at least imatinib therapy between June 2, 2020, and Feb 14, 2023, in multicenters were retrospectively analyzed. The PFS, overall survival (OS), objective response rate (ORR), disease control rate (DCR) and safety were assessed and analyzed. The study was approved by the Ethics Committee of the First Affiliated Hospital with Nanjing Medical University.

Results: A total of 31 GIST patients with primary and secondary KIT mutations were evaluated. The median age was 60 years (range, 41–80 years) and the median number of prior lines of therapy was 3 (range, 1-3). The primary tumor predominantly originated in the small intestine (77.42%) and 38.71% of patients with ECOG performance status of ≥2. At the data cut off on June 7, 2023, the median follow-up duration was 16.6 months (95% CI 12.7-20.5). The median PFS was 11.0 months (95% CI, 2.7-19.3), and the ORR and DCR were 22.58%(n=7) and 93.55%(n=29), respectively. The median OS was 19.7 months (95% CI 11.41-27.99). Secondary mutations were identified in 30 patients with KIT exon 11 mutations (13 in exon 13, 15 in exon 17 and 2 in both exon 13 and 17) and in one patient with KIT exon 9 mutation (both exon 13 and 17). The mPFS was 11.0 months (95% CI 3.04-18.96) for the patients with primary KIT exon 11 and secondary mutations. The patient with a primary KIT exon 9 and secondary mutations exhibited a PFS of 21.2 months. Grade 1-2 treatment-emergent adverse events (TEAEs) occurred in 80.65% of patients, and one patient (3.23%) experienced grade 3 palmar-plantar erythrodysesthesia syndrome.

Conclusion: The prevalence of secondary mutations among patients with primary exon 11 mutations seemes higher than those with exon 9 mutations. Ripretinib demonstrated promising mPFS and mOS benefit for patients with both primary and secondary KIT mutations, which was numerically superior to previously reported mPFS for sunitinib and regorafenib in patients with any secondary mutations.