Peking University Cancer Hospital & Institute, Beijing, China.
The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, China.
Clin Cancer Res. 2022 Aug 15;28(16):3425-3432. doi: 10.1158/1078-0432.CCR-22-0196.
This is a phase II multicenter, single-arm, open-label study assessing the efficacy, safety, and pharmacokinetics (PK) of ripretinib in Chinese patients with advanced gastrointestinal stromal tumor (GIST) as a fourth- or later-line therapy. It was designed to show consistency with the phase III INVICTUS study.
Patients with disease progression on (or intolerance to) prior imatinib, sunitinib, and at least one other drug were recruited to receive ripretinib 150 mg once daily continuously in 28-day cycles. The primary endpoint was progression-free survival (PFS) based on independent radiologic review (IRR). Secondary efficacy endpoints included objective response rate (ORR) based on IRR and overall survival. Safety endpoints included the incidence and severity of adverse events (AE).
Between April 2020 and August 2020, 39 patients were enrolled. All were included in the safety analysis while 38 were included in the efficacy analysis. By primary data cut-off (February 26, 2021), the median PFS [90% confidence interval (CI)] was 7.2 (2.9-7.3) months; the lower bound of the 90% CI exceeded 1 month, fulfilling the standard of bridging success. The ORR (95% CI) based on IRR was 18.4% (7.7%-34.3%). Treatment-related treatment-emergent AEs (TRAE) were reported in 37 (94.9%) patients. The majority of TRAEs were of grade 1/2. A total of 6 patients (15.4%) experienced grade 3/4 TRAEs.
The results demonstrated that ripretinib can clinically improve the outcomes of Chinese patients with advanced GIST as a fourth- or later-line therapy. The efficacy, safety, and PK profiles of ripretinib are consistent with those in the global patient population.
这是一项在中国晚期胃肠间质瘤（GIST）患者中进行的 II 期、多中心、单臂、开放标签研究，评估 ripretinib 作为四线或五线治疗的疗效、安全性和药代动力学（PK）。该研究旨在与 III 期 INVICTUS 研究保持一致。
招募了在（或不耐受）先前的伊马替尼、舒尼替尼和至少一种其他药物治疗后疾病进展的患者，接受 ripretinib 150 mg 每日一次连续 28 天周期治疗。主要终点是基于独立影像学评估（IRR）的无进展生存期（PFS）。次要疗效终点包括基于 IRR 的客观缓解率（ORR）和总生存期。安全性终点包括不良事件（AE）的发生率和严重程度。
在 2020 年 4 月至 2020 年 8 月期间，共招募了 39 名患者。所有患者均纳入安全性分析，其中 38 名患者纳入疗效分析。截至主要数据截止日期（2021 年 2 月 26 日），中位 PFS[90%置信区间（CI）]为 7.2（2.9-7.3）个月；90%CI 的下限超过 1 个月，满足桥接成功标准。基于 IRR 的 ORR（95%CI）为 18.4%（7.7%-34.3%）。报告了 37 名（94.9%）患者的与治疗相关的治疗后出现的不良事件（TRAE）。大多数 TRAE 为 1/2 级。共有 6 名（15.4%）患者发生 3/4 级 TRAE。
结果表明，ripretinib 可作为四线或五线治疗，为中国晚期 GIST 患者的临床结局带来改善。ripretinib 的疗效、安全性和 PK 特征与全球患者人群一致。
