In a phase III trial reported in The Lancet Oncology, Shuch et al found that zirconium Zr-89–labeled girentuximab (Zr-89 girentuximab) positron-emission tomography/computed tomography (PET-CT) imaging was accurate in detecting clear cell renal cell carcinoma (RCC) in patients with renal masses. Zr-89 girentuximab has high affinity for carbonic anhydrase 9, a tumor antigen highly expressed in clear cell RCC.
Study Details
In the study, patients from sites in nine countries (United States, Australia, Canada, United Kingdom, Turkiye, Belgium, the Netherlands, Spain, and France) were enrolled between August 2019 and July 2022. A total of 300 patients with an indeterminate renal mass up to 7 cm suspicious for clear cell RCC and scheduled for nephrectomy received a single dose of Zr-89 girentuximab (37 MBq ± 10%; 10 mg of girentuximab) followed by abdominal PET-CT 5 days (± 2 days) later. Surgery was performed no later than 90 days after administration Zr-89 girentuximab. A total of 284 patients (95%), who had evaluable PET-CT findings and confirmed histopathologic diagnosis made by three independent readers were included in the primary analysis.
Key Findings
Zr-89 girentuximab PET-CT had a mean (across three readers) sensitivity of 85.5% (95% confidence interval [CI] = 81.5%–89.6%%) and a mean specificity of 87.0% (95% CI = 81.0%–93.1%) for clear cell RCC. Mean positive predictive value was 92.9% (95% CI = 90.2%–95.7%), mean negative predictive value was 75.2% (95% CI = 71.2%–79.3%), and mean accuracy was 86.0% (95% CI = 85.0%–87.0%).
Most adverse events were considered unlikely to be related or not related to Zr-89 girentuximab, with 193 of 261 adverse events of any grade (74%) occurring during or after surgery. The most common grade ≥ 3 adverse events were postprocedural hemorrhage (2%), urinary retention (1%), and hypertension (1%). A total of 52 serious adverse events occurred in 25 patients (8%), with 51 (98%) occurring after surgery. A total of 13 adverse events in eight patients (3%) were considered possibly or definitely related to Zr-89 girentuximab, including diarrhea, abdominal pain, fatigue, asthenia, pyrexia, hypoesthesia, back pain, urinary retention, dysuria, night sweats, and increased urine output. No treatment-related deaths were reported.
The investigators concluded: “Our results suggest that [Zr-89 girentuximab] PET-CT has a favourable safety profile and is a highly accurate, noninvasive imaging modality for the detection and characterisation of clear cell renal cell carcinoma, which has the potential to be practice changing.”
Brian Shuch, MD, of the Institute for Urologic Oncology, University of California Los Angeles, is the corresponding author of The Lancet Oncology article.
Disclosure: The study was funded by Telix Pharmaceuticals. For full disclosures of the study authors, visit thelancet.com.
