Oncogenic RET fusions occur in diverse cancers. Pralsetinib is a potent, selective inhibitor of RET receptor tyrosine kinase. ARROW (NCT03037385, ongoing) was designed to evaluate pralsetinib efficacy and safety in patients with advanced RET-altered solid tumors. Twenty-nine patients with 12 different RET fusion–positive solid tumor types, excluding non-small-cell lung cancer and thyroid cancer, who had previously received or were not candidates for standard therapies, were enrolled. The most common RET fusion partners in 23 efficacy-evaluable patients were CCDC6 (26%), KIF5B (26%) and NCOA4 (13%). Overall response rate, the primary endpoint, was 57% (95% confidence interval, 35–77) among these patients. Responses were observed regardless of tumor type or RET fusion partner. Median duration of response, progression-free survival and overall survival were 12 months, 7 months and 14 months, respectively. The most common grade ≥3 treatment-related adverse events were neutropenia (31%) and anemia (14%). These data validate RET as a tissue-agnostic target with sensitivity to RET inhibition, indicating pralsetinib’s potential as a well-tolerated treatment option with rapid, robust and durable anti-tumor activity in patients with diverse RET fusion–positive solid tumors.

致癌RET融合发生在多种癌症中。Pralsetinib 是一种有效的、选择性的 RET 受体酪氨酸激酶抑制剂。ARROW（NCT03037385，正在进行）旨在评估 pralsetinib 对晚期RET改变实体瘤患者的疗效和安全性。纳入了 29 名患有 12 种不同 RET 融合阳性实体瘤类型的患者（不包括非小细胞肺癌和甲状腺癌），他们之前接受过标准治疗或不是标准治疗的候选者。23 名可评估疗效的患者中最常见的RET融合伴侣是CCDC6 (26%)、KIF5B (26%) 和NCOA4 (13%)。这些患者的总体缓解率（主要终点）为 57%（95% 置信区间，35-77）。无论肿瘤类型或RET融合伙伴如何，都会观察到反应。中位缓解持续时间、无进展生存期和总生存期分别为 12 个月、7 个月和 14 个月。最常见的≥3级治疗相关不良事件是中性粒细胞减少症（31%）和贫血（14%）。这些数据验证了 RET 作为一种与组织无关的靶点，对 RET 抑制敏感，表明普拉替尼有潜力作为一种耐受性良好的治疗选择，在多种 RET 融合阳性实体瘤患者中具有快速、强大和持久的抗肿瘤活性。