The University of Texas MD Anderson Cancer Center, Houston, Texas.
Roswell Park Cancer Institute, Buffalo, New York.
Cancer Discov. 2020 May;10(5):657-663. doi: 10.1158/2159-8290.CD-19-1265. Epub 2020 Feb 6.
mutations occur in a wide range of tumor types, and RAF inhibition has become standard in several of these cancers. Despite this progress, mutations have historically been considered a clear demonstration of tumor lineage context-dependent oncogene addiction, based predominantly on the insensitivity to RAF inhibition in colorectal cancer. However, the true broader activity of RAF inhibition pan-cancer remains incompletely understood. To address this, we conducted a multicohort "basket" study of the BRAF inhibitor vemurafenib in non-melanoma mutation-positive solid tumors. In total, 172 patients with 26 unique cancer types were treated, achieving an overall response rate of 33% and median duration of response of 13 months. Responses were observed in 13 unique cancer types, including historically treatment-refractory tumor types such as cholangiocarcinoma, sarcoma, glioma, neuroendocrine carcinoma, and salivary gland carcinomas. Collectively, these data demonstrate that single-agent BRAF inhibition has broader clinical activity than previously recognized. SIGNIFICANCE: These data suggest that mutations lead to oncogene addiction and are clinically actionable in a broad range of non-melanoma cancers, including tumor types in which RAF inhibition is not currently considered standard of care...
突变发生在广泛的肿瘤类型中，RAF 抑制已成为其中几种癌症的标准治疗方法。尽管取得了这一进展，但基于结直肠癌对 RAF 抑制的不敏感性，突变在历史上一直被认为是肿瘤谱系依赖性致癌基因成瘾的明确表现，主要基于结直肠癌对 RAF 抑制的不敏感性。然而，RAF 抑制在泛癌中的真正更广泛的活性仍未被完全理解。为了解决这个问题，我们对 BRAF 抑制剂 vemurafenib 在非黑色素瘤突变阳性实体肿瘤中的多队列“篮子”研究进行了研究。共有 172 名患有 26 种独特癌症类型的患者接受了治疗，总体缓解率为 33%，中位缓解持续时间为 13 个月。在 13 种独特的癌症类型中观察到了反应，包括胆管癌、肉瘤、神经胶质瘤、神经内分泌癌和唾液腺癌等历史上治疗耐药的肿瘤类型。总之，这些数据表明，单一药物 BRAF 抑制具有比以前认识到的更广泛的临床活性。意义：这些数据表明，突变导致致癌基因成瘾，并在广泛的非黑色素瘤癌症中具有临床可操作性，包括 RAF 抑制目前不被认为是标准治疗的肿瘤类型。
