Vishnu Murthy, Andrew F. Voter, Kathleen Nguyen, Martin Allen-Auerbach, Lucia Chen, Sydney Caputo, Elisa Ledet, Abraham Akerele, Abuzar Moradi Tuchayi, Courtney Lawhn-Heath, Tingchang Wang, Michael A. Carducci, Martin G. Pomper, Channing J. Paller, Johannes Czernin, Lilja B. Solnes, Thomas A. Hope, Oliver Sartor, Jeremie Calais, Andrei Gafita
{"title":"[177Lu]Lu-PSMA-617治疗转移性阉割耐药前列腺癌的疗效和毒性:美国扩大准入计划的结果以及与 VISION 3 期数据的比较","authors":"Vishnu Murthy, Andrew F. Voter, Kathleen Nguyen, Martin Allen-Auerbach, Lucia Chen, Sydney Caputo, Elisa Ledet, Abraham Akerele, Abuzar Moradi Tuchayi, Courtney Lawhn-Heath, Tingchang Wang, Michael A. Carducci, Martin G. Pomper, Channing J. Paller, Johannes Czernin, Lilja B. Solnes, Thomas A. Hope, Oliver Sartor, Jeremie Calais, Andrei Gafita","doi":"10.2967/jnumed.124.267816","DOIUrl":null,"url":null,"abstract":"<p>The phase 3 VISION trial demonstrated that [<sup>177</sup>Lu]Lu-PSMA-617 prolonged progression-free survival and overall survival (OS) in prostate-specific membrane antigen [PSMA]–positive metastatic castration-resistant prostate cancer (mCRPC) patients who progressed on taxane-based chemotherapy and androgen receptor–signaling inhibitors (ARSIs). The U.S. expanded-access program (EAP; NCT04825652) was opened to provide access to [<sup>177</sup>Lu]Lu-PSMA-617 for eligible patients until regulatory approval was obtained. This study aimed to evaluate the efficacy and safety profile of [<sup>177</sup>Lu]Lu-PSMA-617 within the EAP and compare the results with those from the VISION trial. <strong>Methods:</strong> Patients enrolled in the EAP at 4 institutions in the United States with available toxicity and outcome data were included. Outcome measures included OS, a prostate-specific antigen (PSA) response rate (RR) of at least 50%, and incidences of toxicity according to Common Terminology Criteria for Adverse Events version 5.0. Differences in baseline characteristics, outcome data, and toxicity between the EAP and VISION were evaluated using <em>t</em> testing of proportions and survival analyses. <strong>Results:</strong> In total, 117 patients with mCRPC who received [<sup>177</sup>Lu]Lu-PSMA-617 within the EAP between May 2021 and March 2022 were eligible and included in this analysis. Patients enrolled in the EAP were more heavily pretreated with ARSI (≥2 ARSI regimens: 70% vs. 46%; <em>P</em> < 0.001) and had worse performance status at baseline (Eastern Cooperative Oncology Group score ≥ 2: 19% vs. 7%; <em>P</em> < 0.001) than VISION patients. EAP and VISION patients had similar levels of grade 3 or higher anemia (18% vs. 13%; <em>P</em> = 0.15), thrombocytopenia (13% vs. 8%; <em>P</em> = 0.13), and neutropenia (3% vs. 3%; <em>P</em> = 0.85) and similar PSA RRs (42% vs. 46%; <em>P</em> = 0.50) and OS (median: 15.1 vs. 15.3 mo; <em>P</em> > 0.05). <strong>Conclusion:</strong> Patients with PSMA-positive mCRPC who received [<sup>177</sup>Lu]Lu-PSMA-617 within the EAP were later in their disease trajectory than VISION patients. Patients enrolled in the EAP achieved similar PSA RRs and OS and had a safety profile similar to that of the VISION trial patients.</p>","PeriodicalId":22820,"journal":{"name":"The Journal of Nuclear Medicine","volume":null,"pages":null},"PeriodicalIF":0.0000,"publicationDate":"2024-09-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Efficacy and Toxicity of [177Lu]Lu-PSMA-617 for Metastatic Castration-Resistant Prostate Cancer: Results from the U.S. Expanded-Access Program and Comparisons with Phase 3 VISION Data\",\"authors\":\"Vishnu Murthy, Andrew F. Voter, Kathleen Nguyen, Martin Allen-Auerbach, Lucia Chen, Sydney Caputo, Elisa Ledet, Abraham Akerele, Abuzar Moradi Tuchayi, Courtney Lawhn-Heath, Tingchang Wang, Michael A. Carducci, Martin G. Pomper, Channing J. Paller, Johannes Czernin, Lilja B. Solnes, Thomas A. Hope, Oliver Sartor, Jeremie Calais, Andrei Gafita\",\"doi\":\"10.2967/jnumed.124.267816\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p>The phase 3 VISION trial demonstrated that [<sup>177</sup>Lu]Lu-PSMA-617 prolonged progression-free survival and overall survival (OS) in prostate-specific membrane antigen [PSMA]–positive metastatic castration-resistant prostate cancer (mCRPC) patients who progressed on taxane-based chemotherapy and androgen receptor–signaling inhibitors (ARSIs). The U.S. expanded-access program (EAP; NCT04825652) was opened to provide access to [<sup>177</sup>Lu]Lu-PSMA-617 for eligible patients until regulatory approval was obtained. This study aimed to evaluate the efficacy and safety profile of [<sup>177</sup>Lu]Lu-PSMA-617 within the EAP and compare the results with those from the VISION trial. <strong>Methods:</strong> Patients enrolled in the EAP at 4 institutions in the United States with available toxicity and outcome data were included. Outcome measures included OS, a prostate-specific antigen (PSA) response rate (RR) of at least 50%, and incidences of toxicity according to Common Terminology Criteria for Adverse Events version 5.0. Differences in baseline characteristics, outcome data, and toxicity between the EAP and VISION were evaluated using <em>t</em> testing of proportions and survival analyses. <strong>Results:</strong> In total, 117 patients with mCRPC who received [<sup>177</sup>Lu]Lu-PSMA-617 within the EAP between May 2021 and March 2022 were eligible and included in this analysis. Patients enrolled in the EAP were more heavily pretreated with ARSI (≥2 ARSI regimens: 70% vs. 46%; <em>P</em> < 0.001) and had worse performance status at baseline (Eastern Cooperative Oncology Group score ≥ 2: 19% vs. 7%; <em>P</em> < 0.001) than VISION patients. EAP and VISION patients had similar levels of grade 3 or higher anemia (18% vs. 13%; <em>P</em> = 0.15), thrombocytopenia (13% vs. 8%; <em>P</em> = 0.13), and neutropenia (3% vs. 3%; <em>P</em> = 0.85) and similar PSA RRs (42% vs. 46%; <em>P</em> = 0.50) and OS (median: 15.1 vs. 15.3 mo; <em>P</em> > 0.05). <strong>Conclusion:</strong> Patients with PSMA-positive mCRPC who received [<sup>177</sup>Lu]Lu-PSMA-617 within the EAP were later in their disease trajectory than VISION patients. Patients enrolled in the EAP achieved similar PSA RRs and OS and had a safety profile similar to that of the VISION trial patients.</p>\",\"PeriodicalId\":22820,\"journal\":{\"name\":\"The Journal of Nuclear Medicine\",\"volume\":null,\"pages\":null},\"PeriodicalIF\":0.0000,\"publicationDate\":\"2024-09-26\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"The Journal of Nuclear Medicine\",\"FirstCategoryId\":\"1085\",\"ListUrlMain\":\"https://doi.org/10.2967/jnumed.124.267816\",\"RegionNum\":0,\"RegionCategory\":null,\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"\",\"JCRName\":\"\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"The Journal of Nuclear Medicine","FirstCategoryId":"1085","ListUrlMain":"https://doi.org/10.2967/jnumed.124.267816","RegionNum":0,"RegionCategory":null,"ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"","JCRName":"","Score":null,"Total":0}
引用次数: 0
摘要
VISION 3 期试验表明,[177Lu]Lu-PSMA-617 延长了前列腺特异性膜抗原 [PSMA] 阳性转移性去势抵抗性前列腺癌 (mCRPC) 患者的无进展生存期和总生存期 (OS),这些患者在接受以紫杉类药物为主的化疗和雄激素受体信号转导抑制剂 (ARSI) 治疗后病情有所进展。美国扩大准入计划(EAP;NCT04825652)已经启动,为符合条件的患者提供[177Lu]Lu-PSMA-617,直至获得监管部门批准。本研究旨在评估 EAP 中 [177Lu]Lu-PSMA-617 的疗效和安全性,并将其结果与 VISION 试验的结果进行比较。研究方法:纳入美国 4 家机构的 EAP 入组患者,并提供毒性和结果数据。结果指标包括OS、至少50%的前列腺特异性抗原(PSA)反应率(RR)以及符合不良事件通用术语标准5.0版的毒性发生率。通过比例 t 检验和生存分析评估了 EAP 和 VISION 在基线特征、结果数据和毒性方面的差异。结果在2021年5月至2022年3月期间,共有117名mCRPC患者在EAP内接受了[177Lu]Lu-PSMA-617治疗,符合条件并纳入本分析。与 VISION 患者相比,EAP 患者接受了更多的 ARSI 预处理(≥2 种 ARSI 方案:70% 对 46%;P <;0.001),基线时的表现状态更差(东部合作肿瘤学组评分≥2:19% 对 7%;P <;0.001)。EAP和VISION患者的3级或3级以上贫血(18% vs. 13%; P = 0.15)、血小板减少(13% vs. 8%; P = 0.13)和中性粒细胞减少(3% vs. 3%; P = 0.85)程度相似,PSA RRs(42% vs. 46%; P = 0.50)和OS(中位:15.1月 vs. 15.3月; P > 0.05)程度相似。结论在EAP内接受[177Lu]Lu-PSMA-617治疗的PSMA阳性mCRPC患者的疾病轨迹晚于VISION患者。参加 EAP 的患者获得了相似的 PSA RRs 和 OS,其安全性与 VISION 试验患者相似。
Efficacy and Toxicity of [177Lu]Lu-PSMA-617 for Metastatic Castration-Resistant Prostate Cancer: Results from the U.S. Expanded-Access Program and Comparisons with Phase 3 VISION Data
The phase 3 VISION trial demonstrated that [177Lu]Lu-PSMA-617 prolonged progression-free survival and overall survival (OS) in prostate-specific membrane antigen [PSMA]–positive metastatic castration-resistant prostate cancer (mCRPC) patients who progressed on taxane-based chemotherapy and androgen receptor–signaling inhibitors (ARSIs). The U.S. expanded-access program (EAP; NCT04825652) was opened to provide access to [177Lu]Lu-PSMA-617 for eligible patients until regulatory approval was obtained. This study aimed to evaluate the efficacy and safety profile of [177Lu]Lu-PSMA-617 within the EAP and compare the results with those from the VISION trial. Methods: Patients enrolled in the EAP at 4 institutions in the United States with available toxicity and outcome data were included. Outcome measures included OS, a prostate-specific antigen (PSA) response rate (RR) of at least 50%, and incidences of toxicity according to Common Terminology Criteria for Adverse Events version 5.0. Differences in baseline characteristics, outcome data, and toxicity between the EAP and VISION were evaluated using t testing of proportions and survival analyses. Results: In total, 117 patients with mCRPC who received [177Lu]Lu-PSMA-617 within the EAP between May 2021 and March 2022 were eligible and included in this analysis. Patients enrolled in the EAP were more heavily pretreated with ARSI (≥2 ARSI regimens: 70% vs. 46%; P < 0.001) and had worse performance status at baseline (Eastern Cooperative Oncology Group score ≥ 2: 19% vs. 7%; P < 0.001) than VISION patients. EAP and VISION patients had similar levels of grade 3 or higher anemia (18% vs. 13%; P = 0.15), thrombocytopenia (13% vs. 8%; P = 0.13), and neutropenia (3% vs. 3%; P = 0.85) and similar PSA RRs (42% vs. 46%; P = 0.50) and OS (median: 15.1 vs. 15.3 mo; P > 0.05). Conclusion: Patients with PSMA-positive mCRPC who received [177Lu]Lu-PSMA-617 within the EAP were later in their disease trajectory than VISION patients. Patients enrolled in the EAP achieved similar PSA RRs and OS and had a safety profile similar to that of the VISION trial patients.