Sunitinib, a multitargeted tyrosine kinase inhibitor (TKI), is approved for advanced gastrointestinal stromal tumor (GIST) after imatinib failure. Ripretinib is a switch-control TKI approved for advanced GIST after prior treatment with three or more TKIs, including imatinib. We compared efficacy and safety of ripretinib versus sunitinib in patients with advanced GIST who were previously treated with imatinib (INTRIGUE, ClinicalTrials.gov identifier: NCT03673501).

Random assignment was 1:1 to once-daily ripretinib 150 mg or once-daily sunitinib 50 mg (4 weeks on/2 weeks off) and stratified by KIT/platelet-derived growth factor α mutation and imatinib intolerance. The primary end point was progression-free survival (PFS) by independent radiologic review using modified Response Evaluation Criteria in Solid Tumors version 1.1. Secondary end points included objective response rate by independent radiologic review, safety, and patient-reported outcome measures.

Overall, 453 patients were randomly assigned to ripretinib (intention-to-treat [ITT], n = 226; KIT exon 11 ITT, n = 163) or sunitinib (ITT, n = 227; KIT exon 11 ITT, n = 164). Median PFS for ripretinib and sunitinib (KIT exon 11 ITT) was 8.3 and 7.0 months, respectively (hazard ratio, 0.88; 95% CI, 0.66 to 1.16; P = .36); median PFS (ITT) was 8.0 and 8.3 months, respectively (hazard ratio, 1.05; 95% CI, 0.82 to 1.33; nominal P = .72). Neither was statistically significant. Objective response rate was higher for ripretinib versus sunitinib in the KIT exon 11 ITT population (23.9% v 14.6%, nominal P = .03). Ripretinib was associated with a more favorable safety profile, fewer grade 3/4 treatment-emergent adverse events (41.3% v 65.6%, nominal P < .0001), and better scores on patient-reported outcome measures of tolerability.

Ripretinib was not superior to sunitinib in terms of PFS. However, meaningful clinical activity, fewer grade 3/4 treatment-emergent adverse events, and improved tolerability were observed with ripretinib.

舒尼替尼是一种多靶点酪氨酸激酶抑制剂 (TKI)，被批准用于伊马替尼治疗失败后的晚期胃肠道间质瘤 (GIST)。Ripretinib 是一种开关控制 TKI，在先前使用三种或更多 TKI（包括伊马替尼）治疗后获准用于晚期 GIST。我们比较了利普替尼与舒尼替尼在先前接受过伊马替尼治疗的晚期 GIST 患者中的疗效和安全性（INTRIGUE，ClinicalTrials.gov 标识符：NCT03673501）。

随机分配为 1:1 每日一次 ripretinib 150 mg 或每日一次舒尼替尼 50 mg（服用 4 周/停药 2 周），并根据KIT /血小板衍生生长因子 α突变和伊马替尼不耐受进行分层。主要终点是无进展生存期（PFS），通过独立的放射学审查，使用修改后的实体瘤反应评估标准 1.1 版。次要终点包括独立放射学审查的客观反应率、安全性和患者报告的结果测量。

总体而言，453 名患者被随机分配至利培替尼（意向治疗 [ITT]，n = 226；KIT外显子 11 ITT，n = 163）或舒尼替尼（ITT，n = 227；KIT外显子 11 ITT，n = 164） . ripretinib 和舒尼替尼（KIT外显子 11 ITT）的中位 PFS 分别为 8.3 和 7.0 个月（风险比，0.88；95% CI，0.66 至 1.16；P = .36）；中位 PFS (ITT) 分别为 8.0 和 8.3 个月（风险比，1.05；95% CI，0.82 至 1.33；标称P = .72）。两者均无统计学意义。在KIT外显子 11 ITT 人群中，ripretinib 的客观缓解率高于舒尼替尼（23.9%对14.6%，标称P=.03）。Ripretinib 具有更有利的安全性、更少的 3/4 级治疗紧急不良事件（41.3%对65.6%，标称P <.0001）以及患者报告的耐受性结果测量得分更高。

就 PFS 而言，利培替尼并不优于舒尼替尼。然而，使用利培替尼观察到有意义的临床活动、较少的 3/4 级治疗紧急不良事件和改善的耐受性。