Marked, Homogeneous, and Early [18F]Fluorodeoxyglucose-Positron Emission Tomography Responses to Vemurafenib in BRAF-Mutant Advanced Melanoma
Marked, Homogeneous, and Early [18F]Fluorodeoxyglucose-Positron Emission Tomography Responses to Vemurafenib in BRAF-Mutant Advanced Melanoma
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DOI：
10.1200/jco.2011.39.1938
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发表时间：
2012-05-10
影响因子：
45.3
通讯作者：
Hicks, Rodney J.
中科院分区：
文献类型：
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作者：
McArthur, Grant A.;Puzanov, Igor;Hicks, Rodney J.
目的使用[F-18]氟脱氧葡萄糖(FDG)-正电子发射断层扫描（PET）成像可以早期识别针对人类癌症关键驱动突变的药物的反应。我们的目的是确定晚期braf突变黑色素瘤患者对vemurafenib的代谢反应率。基线和第15天fpg - pet在31例晚期黑色素瘤患者中进行了vemurafenib （PLX06-02）剂量递增的I期研究，其中4例患者接受亚治疗剂量治疗，24例患者接受960mg每天两次的治疗，这是vemurafenib的最大耐受剂量。结果27例患者均达到潜在治疗水平，至少有部分代谢反应，3例患者达到完全代谢反应。在27例患者中，靶病变的最大标准化摄取值（SUVmax）降低了80% +/- 3%，所有确定的疾病部位的注射剂量百分比（%ID）降低了87% +/- 3%。所有已确诊疾病的% ID与靶病变SUVmax呈正相关(r(2) = 0.66；P < 0.001)，表明个体患者病变之间的反应具有显著的同质性。尽管根据RECIST（实体肿瘤反应评价标准），目标病变SUVmax的减少与最佳反应之间没有关系，但FDG摄取减少较多的患者有更长的无进展生存期的趋势。结论fdg - pet是对vemurafenib早期生物学反应的有效标志物。在个别患者的病变之间发现PET反应的差异很小，这表明患者体内的分子异质性很小。FDG-PET是评估抑制突变BRAF的生物学影响的有用工具，并可能允许更有效地开发新型药物。
PurposeImaging with [F-18]fluorodeoxyglucose (FDG)-positron emission tomography (PET) allows early recognition of a response to agents that target key driver mutations in human cancer. We aimed to determine the metabolic response rate to vemurafenib in patients with advanced BRAF-mutant melanoma.Patients and MethodsBaseline and day 15 FDG-PET was evaluated in 31 patients with advanced melanoma treated in a phase I study of dose escalation of vemurafenib (PLX06-02), which included four patients treated at subtherapeutic doses and 24 patients treated at 960 mg twice a day, which is the maximum-tolerated dose of vemurafenib.ResultsAll 27 patients treated at potentially therapeutic levels had at least a partial metabolic response, and three patients achieved a complete metabolic response. In the 27 patients, there was an 80% +/- 3% reduction in the maximum standardized uptake value (SUVmax) of target lesions and an 87% +/- 3% decrease in the percentage of injected dose (%ID) in all identified disease sites. There was a positive correlation between % ID in all identified disease and target-lesion SUVmax (r(2) = 0.66; P < .001) that indicated a significant homogeneity of the response between lesions in individual patients. Although no relationship was found between the reduction in target lesion SUVmax and best response according to RECIST (Response Evaluation Criteria in Solid Tumors), there was a trend for patients with greater reductions in uptake of FDG to have longer progression-free survival.ConclusionFDG-PET is a useful marker of an early biologic response to vemurafenib. Little variability in PET response was found between lesions in individual patients, which suggested minimal intrapatient molecular heterogeneity. FDG-PET is a useful tool for the evaluation of the biologic impact of inhibiting mutant BRAF and may allow for the more effective development of novel agents.