105 - Use of Gadolinium Nanoparticles as Radiosensitizers for Brain Metastases: Results from the Phase 2 Multicentric Randomized Trial (NANORAD2)
Presenter(s)
C. Verry1, J. Villa1, A. Leboucher1, S. Dufort2, F. Boux2, O. de Beaumont2, P. Lesueur3, J. Jacob4, P. Giraud5, A. Stefani6, M. Loo7, G. Noel8, G. Truc9, C. Chira10, A. D'hombre11, N. Milhade12, M. Gataleta1, A. Vilotitch13, M. Roustit14, G. Le Duc2, and J. Balosso15; 1Grenoble Alpes University, CHU Grenoble Alpes, Radiotherapy, INSERM UA7, Grenoble, France, 2NH TherAguix, Grenoble, France, 3Centre François Baclesse, CAEN, France, 4University Hospitals Pitié-Salpêtrière, Paris, France, 5Hôpital Européen Georges Pompidou, Université Paris Cité, Service d'Oncologie Radiothérapie, Paris, France, 6Institut de Cancérologie de Lorraine ICL Alexis Vautrin, Nancy, France, 7Department of Radiation Oncology, Institut Curie, Saint-Cloud, France, 8Paul Strauss Cancer Centre-Unicancer, STRASBOURG, France, 9Centre Georges-François Leclerc, Dijon, France, 10IUCT-Oncopole, Radiation Oncology, Toulouse, France, 11Centre Hospitalier Lyon Sud, Service Radiothérapie, Lyon, France, 12Institut Bergonié, Bordeaux, France, 13Grenoble Alpes University, CHU Grenoble Alpes, Pôle Santé Publique, Grenoble, France, 14Grenoble Alpes University, CHU Grenoble Alpes, Inserm CIC1406, HP2 U1300, Pôle Santé Publique, Grenoble, France, 15Centre Hospitalier Universitaire Grenoble-Alpes, Grenoble, France
Purpose/Objective(s): To evaluate the efficacy and safety of intravenous gadolinium nanoparticles (AGuIX) as a radiosensitizer in patients with multiple brain metastases treated with whole brain radiation therapy (WBRT) in a multicentric, randomized phase II trial.
Materials/Methods: This prospective, multicenter, randomized phase II clinical trial included patients with multiple brain metastases deemed unsuitable for stereotactic radiation therapy. Participants were randomly assigned 1:1 to receive WBRT (30 Gy in 10 fractions) or WBRT plus 3 injections of AGuIX at 100 mg/kg. The primary endpoint was the best objective intracranial response rate, defined as complete and partial response, at 6 weeks and 3 months, assessed by MRI based on modified RECIST criteria, with blinded centralized review. Secondary endpoints included overall survival (OS), intracranial progression-free survival (iPFS), quality of life, neurocognitive function, safety, and AGuIX uptake on MRI.
Results: Between 2019 and 2023, 106 patients were enrolled across 11 centers, with 98 patients included in the full analysis set. The median age at enrollment was 61 years (range: 52-70). Seventy-three percent had more than 10 brain metastases, 60% exhibited neurological symptoms, and 54% had a DS-GPA score > 1. The primary tumor histology included 63% lung cancer, 14% breast cancer, 7% melanoma, and 16% other cancers. No significant difference was observed in the best response rate at 6 weeks and 3 months: 58% in the WBRT group vs. 49% in the WBRT+AGuIX group (p = 0.42). Median iPFS was 4.7 months in the WBRT group and 6.0 months in the WBRT+AGuIX group (HR = 0.85, 95% CI: 0.55-1.33). Median OS was 6.6 months in the WBRT group and 9.6 months in the WBRT+AGuIX group (HR = 1.04, 95% CI: 0.68-1.62). MRI analysis demonstrated significant AGuIX uptake in all brain metastases, with a median signal enhancement of 67%, while healthy brain tissue showed no significant uptake.
Conclusion: The primary endpoint was not met in this palliative cohort. A positive trend was observed in overall survival and intracranial control. These results suggest that AGuIX may have potential as a radiosensitizer in the treatment of brain metastases. Further clinical trials with a more homogeneous patient population and improved prognostic outcomes are warranted.