Abstract：
OBJECTIVE: Anaplastic thyroid carcinoma (ATC) has a poor survival. The combination of Dabrafenib plus Trametinib (DT) had a significant impact in survival of BRAF p.V600E patients. However, durable responses may be compromised by resistance. We aim to present our experience with DT in BRAF positive ATC patients and compare the outcomes with usual therapy, and to study tumor molecular alterations in the DT group.
METHODS: Patients treated between May 2018 and April 2022 in a tertiary referral center, assessed for BRAF status were included. Patients were divided in three groups: BRAF p.V600E treated with DT, BRAF wild type (WT) under multimodal therapy (MT), and BRAF WT under compassionate care (CC). Response was assessed monthly in the first 6 months and every 3 months afterwards, by RECIST 1.1. Overall survival (OS) and progression-free survival (PFS) were estimated with the Kaplan-Meier method and compared with the log-rank test.
RESULTS: Twenty-seven ATC patients were included (DT = 9, MT = 8, and CC = 10). Median OS was 475 days for DT, 156 days for MT, and 39 days for CC (P < .001). At 12 months, only patients in the DT group were alive (71%). Median PFS was 270 days, in the DT group, compared with less than 32 days in BRAF WT (P < .001). No severe adverse events were reported. Molecular profiling showed that in one of the four clinical progressions, a pathogenic NRAS mutation was found.
CONCLUSIONS: Our results show a significant real-world efficacy of Dabrafenib plus Trametinib in both survival and recurrence compared with standard treatment, with a good safety profile.
METHODS: Patients treated between May 2018 and April 2022 in a tertiary referral center, assessed for BRAF status were included. Patients were divided in three groups: BRAF p.V600E treated with DT, BRAF wild type (WT) under multimodal therapy (MT), and BRAF WT under compassionate care (CC). Response was assessed monthly in the first 6 months and every 3 months afterwards, by RECIST 1.1. Overall survival (OS) and progression-free survival (PFS) were estimated with the Kaplan-Meier method and compared with the log-rank test.
RESULTS: Twenty-seven ATC patients were included (DT = 9, MT = 8, and CC = 10). Median OS was 475 days for DT, 156 days for MT, and 39 days for CC (P < .001). At 12 months, only patients in the DT group were alive (71%). Median PFS was 270 days, in the DT group, compared with less than 32 days in BRAF WT (P < .001). No severe adverse events were reported. Molecular profiling showed that in one of the four clinical progressions, a pathogenic NRAS mutation was found.
CONCLUSIONS: Our results show a significant real-world efficacy of Dabrafenib plus Trametinib in both survival and recurrence compared with standard treatment, with a good safety profile.
摘要：
目的：间变性甲状腺癌（ATC）的生存率很低。Dabrafenib联合曲美替尼（DT）对BRAFp.V600E患者的生存率有显著影响。然而,持久的反应可能会受到阻力的影响。我们旨在介绍我们在BRAF阳性ATC患者中使用DT的经验，并将其结果与常规治疗进行比较。并研究DT组的肿瘤分子改变。
方法：2018年5月至2022年4月在三级转诊中心接受治疗的患者，包括评估的BRAF状态。患者分为三组：接受DT治疗的BRAFp.V600E，多模式治疗（MT）下的BRAF野生型（WT），和BRAFWT在同情护理(CC)下。前6个月每月评估一次，之后每3个月评估一次。由RECIST1.1。使用Kaplan-Meier方法估计总生存期（OS）和无进展生存期（PFS），并与对数秩检验进行比较。
结果：纳入27例ATC患者（DT=9，MT=8，CC=10）。DT的中位OS为475天，MT为156天，CC为39天（P<.001）。12个月时,DT组只有患者存活(71%).PFS中位数为270天,在DT组中，与BRAFWT中少于32天相比（P<.001）。未报告严重不良事件。分子谱分析显示，在四个临床进展之一中，发现了致病性NRAS突变。
结论：我们的结果表明，与标准治疗相比，达拉非尼联合曲美替尼在生存和复发方面均具有显著的真实世界疗效。具有良好的安全性。
方法：2018年5月至2022年4月在三级转诊中心接受治疗的患者，包括评估的BRAF状态。患者分为三组：接受DT治疗的BRAFp.V600E，多模式治疗（MT）下的BRAF野生型（WT），和BRAFWT在同情护理(CC)下。前6个月每月评估一次，之后每3个月评估一次。由RECIST1.1。使用Kaplan-Meier方法估计总生存期（OS）和无进展生存期（PFS），并与对数秩检验进行比较。
结果：纳入27例ATC患者（DT=9，MT=8，CC=10）。DT的中位OS为475天，MT为156天，CC为39天（P<.001）。12个月时,DT组只有患者存活(71%).PFS中位数为270天,在DT组中，与BRAFWT中少于32天相比（P<.001）。未报告严重不良事件。分子谱分析显示，在四个临床进展之一中，发现了致病性NRAS突变。
结论：我们的结果表明，与标准治疗相比，达拉非尼联合曲美替尼在生存和复发方面均具有显著的真实世界疗效。具有良好的安全性。
