Second-line treatment patterns and outcomes of advanced gastrointestinal stromal tumor: A real-world study.

Abstract

11526 Background: Ripretinib has emerged as a promising second-line therapy for patients with unresectable or metastatic gastrointestinal stromal tumors (GISTs), demonstrating comparable efficacy to sunitinib and a superior safety profile. However, the optimal second-line therapy tailored to individual patient characteristics remains underexplored. This prospective, multicenter, observational study (NCT05440357) aims to evaluate real-world patterns and outcomes for GISTs patients. Methods: The choice of second-line regimen was determined by the investigators. The primary endpoint was progression-free survival (PFS). Secondary endpoints included safety, objective response rate (ORR), and overall survival (OS). Results: From October 2022, 99 patients were enrolled (ripretinib, n = 49; sunitinib, n = 47; regorafenib, n = 3), with a median follow-up of 8.0 months. Among ripretinib-treated patients, 69% (34/49) had primary KIT exon 11 mutations, while 47% (22/47) of sunitinib-treated patients had primary KIT exon 9 mutations. The objective response rates were 20% (10/49) for ripretinib, 9% (4/47) for sunitinib, and 0% for regorafenib. Median PFS (mPFS) for ripretinib, sunitinib and regorafenib was 11.4, 12.4 and 2.8 months, respectively (p = 0.296). Ripretinib demonstrated better mPFS in patients with primary KIT exon 11 mutations compared to sunitinib group (11.4 vs 7.0 months, p = 0.048). In patients with KIT exon 9 mutations, mPFS was 15.0 months for sunitinib. Ripretinib was associated with fewer grade 3/4 treatment-emergent adverse events (TEAEs) compared to sunitinib (10%vs 26%, p = 0.044). OS data are currently immature. Additionally, 27% (13/49) of patients treated with ripretinib and 17% (8/47) with sunitinib underwent surgery. Among patients who underwent surgery following ripretinib treatment, 84.6% (11/13) achieved R0/R1 resection. 100% (8/8) patients achieved R0/R1 resection in sunitinib group. Median postoperative PFS for ripretinib and sunitinib was 15.5 months and 10.2 months, respectively (p = 0.350). Conclusions: This study is the first prospective, multicenter, real-world study to compare different second-line targeted drugs for advanced GISTs. Our preliminary results suggest that ripretinib may offer superior clinical benefits for patients with primary KIT exon 11 mutations after failure of imatinib first line treatment. Its favorable safety profile and improved tumor response rate facilitated a higher rate of surgical intervention compared to sunitinib. The benefit of surgery remains to be observed. Clinical trial information: NCT05440357 .