Ripretinib, a novel tyrosine kinase inhibitor used in advanced gastrointestinal stromal tumors (GIST) resistant to standard therapies, was assessed in the United Kingdom (UK) within an Expanded Access Program (EAP). A retrospective review of patients treated between January 2020 and October 2021 within the ripretinib EAP in our Institution was conducted. Clinician-documented and mRECIST 1.1 assessments were collected. The primary endpoints were progression-free survival (PFS) and time to treatment discontinuation (TTD). Treatment beyond progression (TBP), overall survival (OS), objective response rates and safety data were also analyzed. Survival curves were constructed using the Kaplan–Meier method, and univariate and multivariate Cox regression analyses were performed. All analyses were performed with R software. Overall, forty-five patients were included. After a median follow-up of 24.2 (95% CI 19.7–29.7) months, the median PFS of the group receiving 150 mg ripretinib once daily (OD) was 7.9 (95% CI 5.6–19.3) months. In the cohort of 22 patients with dose escalation upon tumor progression to 150 mg ripretinib twice daily (BD), the median PFS from BD was 5.4 (95% CI 2.8–9.3) months. Overall, median PFS and OS values for patients on ripretinib were 9.7 (95% CI 8.3–18.1) and 14.0 (95% CI 9.9–NA) months, respectively. TTD was similar to PFS. TBP was observed in about one third of all patients. Objective responses to ripretinib OD and BD treatments were observed in 16.7% and 10.0% of the patients, respectively. No new safety signals were identified. In conclusion, patients with advanced GIST receiving ripretinib in the UK within the EAP reported prolonged benefits, in line with the recent phase III clinical trials.
Ripretinib是一种用于治疗标准疗法无效的晚期胃肠道间质瘤（GIST）的新型酪氨酸激酶抑制剂，本研究通过英国（UK）的扩大可及项目（EAP）对其疗效进行评估。我们对本机构在2020年1月至2021年10月期间参与ripretinib EAP治疗的患者进行了回顾性分析，收集了临床医生记录和mRECIST 1.1评估数据。主要终点为无进展生存期（PFS）和治疗终止时间（TTD），同时分析了进展后继续治疗（TBP）、总生存期（OS）、客观缓解率及安全性数据。采用Kaplan-Meier法绘制生存曲线，并进行单变量与多变量Cox回归分析，所有分析均使用R软件完成。 共纳入45例患者。中位随访24.2个月（95% CI 19.7–29.7）后，每日一次（OD）接受150 mg ripretinib治疗组的中位PFS为7.9个月（95% CI 5.6–19.3）。在肿瘤进展后剂量递增至每日两次（BD）150 mg的22例患者亚组中，剂量递增后的中位PFS为5.4个月（95% CI 2.8–9.3）。总体而言，接受ripretinib治疗患者的中位PFS和OS分别为9.7个月（95% CI 8.3–18.1）与14.0个月（95% CI 9.9–NA）。TTD与PFS结果相近。约三分之一患者出现TBP现象。ripretinib OD与BD治疗的客观缓解率分别为16.7%和10.0%，未发现新的安全性信号。 综上所述，在英国EAP中接受ripretinib治疗的晚期GIST患者获得了持续临床获益，该结果与近期III期临床试验数据一致。
肿瘤(癌症)患者之家