Institute of Urologic Oncology, University of California Los Angeles, Los Angeles, CA, USA.
Institute of Urologic Oncology, University of California Los Angeles, Los Angeles, CA, USA.
Lancet Oncol. 2024 Oct;25(10):1277-1287. doi: 10.1016/S1470-2045(24)00402-9. Epub 2024 Sep 10.
With limitations of conventional imaging and biopsy, accurate, non-invasive techniques to detect clear-cell renal cell carcinoma in patients with renal masses remain an unmet need. Zr-labelled monoclonal antibody ([Zr]Zr-girentuximab) has high affinity for carbonic anhydrase 9, a tumour antigen highly expressed in clear-cell renal cell carcinoma. We aimed to evaluate [Zr]Zr-girentuximab PET-CT imaging for detection and characterisation of clear-cell renal cell carcinoma.
ZIRCON was a prospective, open-label, multicentre, phase 3 trial conducted at 36 research hospitals and practices across nine countries (the USA, Australia, Canada, the UK, Türkiye, Belgium, the Netherlands, Spain, and France). Patients aged 18 years or older with an indeterminate renal mass 7 cm or smaller (cT1) suspicious for clear-cell renal cell carcinoma and scheduled for nephrectomy received a single dose of [Zr]Zr-girentuximab (37 MBq ±10%; 10 mg girentuximab) intravenously followed by abdominal PET-CT imaging 5 days (±2 days) later. Surgery was performed no later than 90 days after administration of [Zr]Zr-girentuximab. Blinded central review, conducted by three independent readers, determined the histology from surgical samples. The coprimary endpoints, determined for each individual reader, were the sensitivity and specificity of [Zr]Zr-girentuximab PET-CT imaging to detect clear-cell renal cell carcinoma, with histopathological confirmation as standard of truth. Analyses were on the full analysis set of patients, defined as patients who had evaluable PET-CT imaging and a confirmed histopathological diagnosis. The trial is registered with ClinicalTrials.gov, NCT03849118, and EUDRA Clinical Trials Register, 2018-002773-21, and is closed to enrolment.
Between Aug 14, 2019, and July 8, 2022, 371 patients were screened for eligibility, 332 of whom were enrolled. 300 patients received [Zr]Zr-girentuximab (214 [71%] male and 86 [29%] female). 284 (95%) evaluable patients were included in the primary analysis. The mean sensitivity was 85·5% (95% CI 81·5-89·6) and mean specificity was 87·0% (81·0-93·1). No safety signals were observed. Most adverse events were not or were unlikely to be related to [Zr]Zr-girentuximab, with most (193 [74%] of 261 events) occurring during or after surgery. The most common grade 3 or worse adverse events were post-procedural haemorrhage (in six [2%] of 261 patients), urinary retention (three [1%]), and hypertension (three [1%]). In 25 (8%) of 300 patients, 52 serious adverse events were reported, of which 51 (98%) occurred after surgery. There were no treatment-related deaths.
Our results suggest that [Zr]Zr-girentuximab PET-CT has a favourable safety profile and is a highly accurate, non-invasive imaging modality for the detection and characterisation of clear-cell renal cell carcinoma, which has the potential to be practice changing.
Telix Pharmaceuticals.
由于传统影像学检查和活检的局限性，对于直径 7cm 或更小的肾占位性病变（cT1 期）疑似透明细胞肾细胞癌的患者，仍需要一种准确、非侵入性的技术来进行检测。Zr 标记的单克隆抗体（[Zr]Zr-吉妥单抗）对高度表达于透明细胞肾细胞癌中的碳酸酐酶 9 具有高亲和力。我们旨在评估 [Zr]Zr-吉妥单抗 PET-CT 成像在透明细胞肾细胞癌的检测和特征分析中的应用。
ZIRCON 是一项在 9 个国家（美国、澳大利亚、加拿大、英国、土耳其、比利时、荷兰、西班牙和法国）的 36 家研究医院和诊所进行的前瞻性、开放性标签、多中心、3 期临床试验。纳入年龄 18 岁及以上、直径 7cm 或更小（cT1 期）的肾占位性病变（疑似透明细胞肾细胞癌）且计划行肾切除术的患者，给予单剂量 [Zr]Zr-吉妥单抗（37MBq±10%；10mg 吉妥单抗）静脉注射，随后在 5 天（±2 天）后进行腹部 PET-CT 检查。[Zr]Zr-吉妥单抗给药后 90 天内进行手术。由三位独立的阅片者进行盲法中心评估，根据手术样本确定组织学诊断。主要终点是每位阅片者确定的 [Zr]Zr-吉妥单抗 PET-CT 成像对透明细胞肾细胞癌的检测敏感性和特异性，以组织病理学为金标准。分析纳入了可评估的 PET-CT 成像和明确的组织病理学诊断的患者的全分析集。该试验在 ClinicalTrials.gov（NCT03849118）和 EUDRA Clinical Trials Register（2018-002773-21）上注册，目前已关闭入组。
2019 年 8 月 14 日至 2022 年 7 月 8 日，共筛选了 371 例患者，其中 332 例符合入组条件。300 例患者接受了 [Zr]Zr-吉妥单抗治疗（214 例男性[71%]，86 例女性[29%]）。284 例（95%）可评估患者纳入了主要分析。平均敏感度为 85.5%（95%CI，81.5-89.6），平均特异性为 87.0%（81.0-93.1）。未观察到安全性信号。大多数不良事件为非或不太可能与 [Zr]Zr-吉妥单抗相关，其中大多数（261 例事件中的 193 例[74%]）发生在手术期间或之后。最常见的 3 级或更高级别的不良事件是术后出血（261 例患者中有 6 例[2%]）、尿潴留（3 例[1%]）和高血压（3 例[1%]）。在 300 例患者中，有 25 例（8%）报告了 52 例严重不良事件，其中 51 例（98%）发生在手术后。无治疗相关死亡。
我们的研究结果表明，[Zr]Zr-吉妥单抗 PET-CT 具有良好的安全性，是一种高度准确、非侵入性的成像方式，可用于检测和特征分析透明细胞肾细胞癌，具有改变临床实践的潜力。
Telix 制药公司。
