From the University of Arizona, Tucson, Ariz (P.H.K.); Memorial Sloan-Kettering Cancer Center, New York, NY (M.J.M.); Invicro, Needham, Mass (J.H.); Mayo Clinic, Rochester, Minn (A.T.K., O.S.); Department of Nuclear Medicine, University Hospital Münster, Münster, Germany (K.R.); West German Cancer Center, Münster and Essen, Germany (K.R.); Dana-Farber Cancer Institute, Boston, Mass (X.X.W.); Astera Cancer Care, East Brunswick, NJ (B.F.); Indiana University Simon Comprehensive Cancer Center, Indianapolis, Ind (N.A.); Miami Cancer Institute, Baptist Health South Florida, Miami, Fla (R.G.); Washington University, St. Louis, Mo (J.M.M.); British Columbia Cancer Agency, Vancouver, British Columbia, Canada (K.C.); The Institute of Cancer Research and Royal Marsden Hospital, London, United Kingdom (J.d.B.); Gustave Roussy Institute, University of Paris-Saclay, Villejuif, France (K.F.); Rostock University Medical Center, Rostock, Germany (B.K.); Weill Cornell Medicine, New York, NY (S.T.T.); Novartis Pharmaceuticals, East Hanover, NJ (S.G.); Novartis Pharmaceuticals, Indianapolis, Ind (M.B.); Novartis Pharmaceuticals, Cambridge, Mass (C.C.W.); Novartis Pharmaceuticals, Geneva, Switzerland (A.M.C.); Novartis Pharmaceuticals, St. George, Utah (T.B.); Duke Cancer Institute Center for Prostate and Urologic Cancers, Duke University, Durham, NC (A.J.A.); and University Hospital Essen and German Cancer Consortium, Hufelandstr. 55, 45147 Essen, Germany (K.H.).
Radiology. 2024 Aug;312(2):e233460. doi: 10.1148/radiol.233460.
Background Lutetium 177 [Lu]Lu-PSMA-617 (Lu-PSMA-617) is a prostate-specific membrane antigen (PSMA)-targeted radioligand therapy for metastatic castration-resistant prostate cancer (mCRPC). Quantitative PSMA PET/CT analysis could provide information on Lu-PSMA-617 treatment benefits. Purpose To explore the association between quantitative baseline gallium 68 [Ga]Ga-PSMA-11 (Ga-PSMA-11) PET/CT parameters and treatment response and outcomes in the VISION trial. Materials and Methods This was an exploratory secondary analysis of the VISION trial. Eligible participants were randomized (June 2018 to October 2019) in a 2:1 ratio to Lu-PSMA-617 therapy (7.4 GBq every 6 weeks for up to six cycles) plus standard of care (SOC) or to SOC only. Baseline Ga-PSMA-11 PET parameters, including the mean and maximum standardized uptake value (SUV and SUV), PSMA-positive tumor volume, and tumor load, were extracted from five anatomic regions and the whole body. Associations of quantitative PET parameters with radiographic progression-free survival (rPFS), overall survival (OS), objective response rate, and prostate-specific antigen response were investigated using univariable and multivariable analyses (with treatment as the only other covariate). Outcomes were assessed in subgroups based on SUV quartiles. Results Quantitative PET parameters were well balanced between study arms for the 826 participants included. The median whole-body tumor SUV was 7.6 (IQR, 5.8-9.9). Whole-body tumor SUV was the best predictor of Lu-PSMA-617 efficacy, with a hazard ratio (HR) range of 0.86-1.43 for all outcomes (all < .001). A 1-unit whole-body tumor SUV increase was associated with a 12% and 10% decrease in risk of an rPFS event and death, respectively. Lu-PSMA-617 plus SOC prolonged rPFS and OS in all SUV quartiles versus SOC only, with no identifiable optimum among participants receiving Lu-PSMA-617. Higher baseline PSMA-positive tumor volume and tumor load were associated with worse rPFS (HR range, 1.44-1.53 [ < .05] and 1.02-1.03 [ < .001], respectively) and OS (HR range, 1.36-2.12 [ < .006] and 1.04 [ < .001], respectively). Conclusion Baseline Ga-PSMA-11 PET/CT whole-body tumor SUV was the best predictor of Lu-PSMA-617 efficacy in participants in the VISION trial. Improvements in rPFS and OS with Lu-PSMA-617 plus SOC were greater among participants with higher whole-body tumor SUV, with evidence for benefit at all SUV levels. ClinicalTrials.gov identifier: NCT03511664 Published under a CC BY 4.0 license.
背景 镥 177[Lu]Lu-PSMA-617（Lu-PSMA-617）是一种用于转移性去势抵抗性前列腺癌（mCRPC）的前列腺特异性膜抗原（PSMA）靶向放射性配体疗法。定量 PSMA PET/CT 分析可为 Lu-PSMA-617 治疗效果提供信息。目的 探讨 VISION 试验中定量基线镓 68[Ga]Ga-PSMA-11（Ga-PSMA-11）PET/CT 参数与治疗反应和结果的关系。材料与方法 这是 VISION 试验的一项探索性二次分析。合格的参与者被随机（2018 年 6 月至 2019 年 10 月）以 2:1 的比例分为 Lu-PSMA-617 治疗组（每 6 周 7.4GBq，最多 6 个周期）加标准治疗（SOC）或仅 SOC。从五个解剖区域和整个身体中提取基线 Ga-PSMA-11 PET 参数，包括平均和最大标准化摄取值（SUV 和 SUV）、PSMA 阳性肿瘤体积和肿瘤负荷。使用单变量和多变量分析（仅以治疗为其他协变量）研究定量 PET 参数与放射性无进展生存期（rPFS）、总生存期（OS）、客观缓解率和前列腺特异性抗原反应的关系。根据 SUV 四分位数评估亚组的结果。结果 纳入的 826 名参与者中，研究臂之间的定量 PET 参数平衡良好。中位全身肿瘤 SUV 为 7.6（IQR，5.8-9.9）。全身肿瘤 SUV 是 Lu-PSMA-617 疗效的最佳预测因子，所有结局（均<0.001）的 HR 范围为 0.86-1.43。全身肿瘤 SUV 增加 1 个单位与 rPFS 事件和死亡风险分别降低 12%和 10%相关。Lu-PSMA-617 加 SOC 与 SOC 相比，在所有 SUV 四分位数中均延长了 rPFS 和 OS，接受 Lu-PSMA-617 治疗的参与者中没有可识别的最佳 SUV 水平。较高的基线 PSMA 阳性肿瘤体积和肿瘤负荷与 rPFS（HR 范围为 1.44-1.53[<0.05]和 1.02-1.03[<0.001]）和 OS（HR 范围为 1.36-2.12[<0.006]和 1.04[<0.001]）较差相关。结论 VISION 试验参与者的基线 Ga-PSMA-11 PET/CT 全身肿瘤 SUV 是 Lu-PSMA-617 疗效的最佳预测因子。Lu-PSMA-617 加 SOC 改善 rPFS 和 OS 的效果在全身肿瘤 SUV 较高的参与者中更大，在所有 SUV 水平均有获益证据。临床试验注册号：NCT03511664 基于 CC BY 4.0 许可发布。
Zotero 插件