Peter MacCallum Cancer Centre, Melbourne, VIC 8006, Australia.
J Clin Oncol. 2012 May 10;30(14):1628-34. doi: 10.1200/JCO.2011.39.1938. Epub 2012 Mar 26.
Imaging with [(18)F]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.
Baseline 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.
All 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.
FDG-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.
使用 [(18)F]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。我们旨在确定晚期 BRAF 突变型黑色素瘤患者接受vemurafenib 治疗后的代谢反应率。
在一项 PLX06-02 剂量递增的vemurafenib （PLX06-02）的 I 期研究中，对 31 例晚期黑色素瘤患者进行了基线和第 15 天 FDG-PET 评估，其中包括 4 例接受亚治疗剂量治疗的患者和 24 例接受每天两次 960mg 的患者，这是 vemurafenib 的最大耐受剂量。
所有接受潜在治疗水平治疗的 27 例患者均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，靶病灶的最大标准化摄取值（SUVmax）降低了 80%±3%，所有识别出的疾病部位的注射剂量百分比（%ID）降低了 87%±3%。所有识别出的疾病部位的 %ID 与靶病灶 SUVmax 之间存在正相关（r(2) = 0.66；P <.001），表明个体患者之间的病变反应具有显著的同质性。虽然未发现根据 RECIST（实体瘤反应评估标准）靶病灶 SUVmax 的降低与最佳反应之间存在关系，但摄取 FDG 的减少与无进展生存期延长的趋势相关。
FDG-PET 是 vemurafenib 早期生物学反应的有用标志物。在个体患者的病变之间发现 PET 反应的变异性很小，这表明患者体内的分子异质性最小。FDG-PET 是评估抑制突变 BRAF 的生物学影响的有用工具，可能有助于更有效地开发新型药物。
