1765P - Second-line targeted therapy patterns and outcomes of advanced gastrointestinal stromal tumor: A prospective, multicentered real-world study

Background

For unresectable or metastatic gastrointestinal stromal tumors (GISTs), sunitinib is the standard second-line treatment. However, other tyrosine kinase inhibitors also demonstrate clinical activity. This prospective, multicenter, observational real-world study aims to explore the second-line targeted therapy patterns and clinical outcomes in GIST patients who progressed on or were intolerant to first-line treatment.

Methods

Patients with advanced GISTs who had progressed or intolerant to first-line therapy were enrolled in the study. The second-line regimen for them was determined based on the judgement by investigators. Enrolment of 100 patients is planned. The primary endpoint is progression-free survival (PFS) by independent radiologic review using modified Response Evaluation Criteria in Solid Tumors version 1.1. Secondary endpoint includes safety.

Results

It is an early result from analysis of 39 patients (ripretinib, n=16; sunitinib, n=20; regorafenib, n=3). Among the patients treated with ripretinib, 81% (13/16) patients had a primary mutation in KIT exon 11. For patients with sunitinib, 55% (11/20) had a primary mutation in KIT exon 9. All patients (100%) with regorafenib carried a secondary mutation in KIT exon 17. Objective response rates were 31% (5/16), 0 and 0 in ripretinib, sunitinib and regorafenib respectively. Median PFS (mPFS) for ripretinib, sunitinib and regorafenib were 11.2, 11.1 and 2.8 months, respectively (P = 0.589). For those with primary KIT exon 11 mutation, mPFS were 10.4, 1.4 and 3.1 months for ripretinib, sunitinib and regorafenib, respectively (P = 0.0045). All grades TEAEs were mostly lower with ripretinib versus sunitinib. And ripretinib was associated with fewer grade 3/4 TEAEs against sunitinib (12.5% vs 40%, p=0.0672).

Conclusions

As a second-line treatment for advanced GIST patients, mPFS was significantly prolonged in the ripretinib group compared to those treated with sunitinib or regorafenib for patients with primary KIT exon 11 mutations. At the same time, ripretinib was associated with lower occurrences of TEAEs with less severity.

Clinical trial identification

NCT05440357 release date: 6/27/2022.

Editorial acknowledgement

Funding

Has not received any funding.

Disclosure

All authors have declared no conflicts of interest.