Zhonghua Wei Chang Wai Ke Za Zhi. 2026 Aug 25;29(8):1058-1066. doi: 10.3760/cma.j.cn441530-20251021-00394.
ABSTRACT
Objective: To investigate the clinical efficacy, safety, and post-resistance treatment strategies of ripretinib in the treatment of advanced gastrointestinal stromal tumors (GIST), and to provide evidence-based references for optimizing individualized treatment of advanced GIST. Methods: This is a single-center retrospective real-world study. Inclusion criteria: (1) GIST confirmed by histopathology; (2) disease progression after previous treatment with other targeted drugs including imatinib; (3) continuous administration of ripretinib for more than one month with at least one efficacy evaluation. Exclusion criteria: (1) Clinical data were seriously missing, and data such as patient dosage, efficacy evaluation results, and adverse reactions could not be obtained; (2) complicated with other serious underlying diseases, such as uncontrolled severe cardiovascular and cerebrovascular diseases, liver and kidney failure, etc.; (3) Allergic or severe drug intolerance to ripretinib. According to the above criteria, a total of 93 patients with advanced GIST treated in West China Hospital of Sichuan University from July 2021 to March 2025 were collected. In this study, evaluable patients were defined as those who met any of the following criteria: (1) baseline and follow-up imaging examinations were completed in our center with complete imaging data, and the long diameter of target lesions could be accurately measured and the efficacy could be evaluated; (2) The efficacy evaluation was completed in other hospitals, but the image data and report were complete, and the exact measurement data of target lesions could be obtained after review by the radiology department of our hospital. All patients with advanced GIST enrolled in the study initially received the standard dose of ripretinib (150 mg once daily). After disease progression (PD), the following treatment strategies could be selected after multi-disciplinary team (MDT) discussion: (1) the dose of ripretinib was increased from 150 mg once daily to 150 mg twice daily (ripretinib dose-escalation group); (2) The standard-dose ripretinib (150 mg, once daily) was combined with local treatment, including surgery, interventional therapy and radiotherapy (ripretinib combined with local treatment group); (3) standard-dose ripretinib combined with frontline TKI, including imatinib, sunitinib and regorafenib (ripretinib combined with frontline TKI group); (4) other TKI treatment, including imatinib, sunitinib, regorafenib and avapritinib (other TKI treatment group). The primary outcome was median progression-free survival (mPFS). Secondary outcomes included objective response rate [ORR, the proportion of patients with complete response (CR) or partial response (PR)], disease control rate [DCR, the proportion of patients with CR, PR, or stable disease (SD)], overall survival (OS), and adverse events. Results: A total of 93 patients with advanced GIST were enrolled. Among 59 evaluable patients, 6 had PR, 30 had SD, and 23 had PD, with ORR of 10.2% and DCR of 61.0%. With a median follow-up time of 13 (2-47) months, the median mPFS was 7.0 (95%CI: 4.9-9.1) months, and the 1-year OS rate was 86.1%. Genotyping analysis showed that the mPFS in the KIT exon 11 mutation group was significantly longer than that in the exon 9 mutation group (12.0 months vs. 4.0 months, P=0.007). No statistically significant difference in mPFS was observed among different recurrence/metastasis sites (liver, peritoneum, or liver + peritoneum, P = 0.149). A total of 60 patients experienced progression on standard-dose ripretinib. According to the subsequent treatment strategy, the patients were divided into 4 groups: ripretinib dose-escalation group (16 patients), ripretinib combined with local therapy group (9 patients), ripretinib combined with frontline TKI group (6 patients), and other TKI group (9 patients). The mPFS in these groups was 4.0 months (95% CI: 1.5-6.5), not reached, 4.0 (95%CI: could not be estimated) and 12.0 months (95%CI: 1.0-25.5), respectively. There was no significant difference in mPFS among the four groups (P=0.345). In terms of safety, no grade 3-4 serious adverse reactions were observed in the whole group, and dose-escalation or combination therapy did not increase toxicity. Conclusion: Ripretinib can serve as an effective treatment option for Chinese patients with advanced GIST after failure of first-line or multiple prior TKI therapies, and it demonstrates a favorable safety profile. Although no standard treatment is currently available for patients with resistance to ripretinib, dose escalation of ripretinib, combination with local therapy, combination with prior TKIs, or switching to alternative TKIs can be considered, and all regimens exhibit a favorable safety profile.
PMID:42706100 | DOI:10.3760/cma.j.cn441530-20251021-00394