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来自1/2期ARROW试验的pralsetinib对RET融合阳性实体瘤患者的泛癌疗效
作者:小柯机器人 发布时间:2022/8/16 17:22:23

美国德州大学MD安德森癌症中心Vivek Subbiah团队近期取得重要工作进展,他们研究报导了来自1/2期ARROW试验的pralsetinib对RET融合阳性实体瘤患者的泛癌疗效。这一研究成果2022年8月12日在线发表于《自然—医学》上。

致癌RET融合发生在多种癌症中。 Pralsetinib 是一种有效的选择性RET受体酪氨酸激酶抑制剂。ARROW(NCT03037385,正在进行中)旨在评估 pralsetinib 在晚期RET改变的实体瘤患者中的疗效和安全性。招募了29名患有12种不同RET融合阳性实体瘤类型(不包括非小细胞肺癌和甲状腺癌)的患者,这些患者之前接受过或不适合标准治疗。23名疗效可评估患者中最常见的RET融合伙伴是CCDC6(26%)、KIF5B(26%)和NCOA4 (13%)。在这些患者中,主要终点的总体反应率为57%(95%置信区间,35-77)。无论肿瘤类型或RET融合伴侣如何,都观察到疗效。缓解期、无进展生存期和总生存期的中位数分别为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是一个对RET抑制敏感的组织不确定靶点,表明pralsetinib作为一种耐受性良好的治疗选择,具有快速、稳健和持久的抗肿瘤活性,可用于多种RET融合阳性实体瘤患者。

附:英文原文

Title: Pan-cancer efficacy of pralsetinib in patients with RET fusion–positive solid tumors from the phase 1/2 ARROW trial

Author: Subbiah, Vivek, Cassier, Philippe A., Siena, Salvatore, Garralda, Elena, Paz-Ares, Luis, Garrido, Pilar, Nadal, Ernest, Vuky, Jacqueline, Lopes, Gilberto, Kalemkerian, Gregory P., Bowles, Daniel W., Seetharam, Mahesh, Chang, Jianhua, Zhang, Hui, Green, Jennifer, Zalutskaya, Alena, Schuler, Martin, Fan, Yun, Curigliano, Giuseppe

Issue&Volume: 2022-08-12

Abstract: 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 12months, 7months and 14months, 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.

DOI: 10.1038/s41591-022-01931-y

Source: https://www.nature.com/articles/s41591-022-01931-y

期刊信息

Nature Medicine:《自然—医学》,创刊于1995年。隶属于施普林格·自然出版集团,最新IF:30.641
官方网址:https://www.nature.com/nm/
投稿链接:https://mts-nmed.nature.com/cgi-bin/main.plex