Nivolumab Switch Maintenance Therapy After Tyrosine Kinase Inhibitor Induction in Metastatic Renal Cell Carcinoma: A Randomized Clinical Trial by the Interdisciplinary Working Group on Renal Tumors of the German Cancer Society (NIVOSWITCH; AIO-NZK-0116ass).

Autor: Grünwald V; Interdisciplinary Genitourinary Oncology, Internal Medicine (Tumor Research) and Urology Clinics, West-German Cancer Center, University Hospital Essen, Essen, Germany. Electronic address: viktor.gruenwald@uk-essen.de., Ivanyi P; Clinic for Hematology, Hemostasis, Oncology and Stem Cell Transplantation, Claudia von Schilling Cancer Center, Medical School Hannover, Hannover, Germany., Zschäbitz S; Department of Medical Oncology, University Hospital Heidelberg, Heidelberg, Germany., Wirth M; Department of Urology, University Hospital Carl Gustav Carus, Technische Universität Dresden, Dresden, Germany., Staib P; Clinic for Hematology and Oncology, St. Antonius Hospital, Eschweiler, Germany., Schostak M; Department of Urology, Uro-Oncology, Robot-Assisted and Focal Therapy, University of Magdeburg, Magdeburg, Germany., Dargatz P; Johannes Wesling Hospital Minden, Minden, Germany., Müller L; Onkologie UnterEms, Leer, Germany., Metz M; Onkologische Schwerpunktpraxis Göttingen, Göttingen, Germany., Bergmann L; Medical Clinic II, University Hospital Frankfurt, Frankfurt, Germany., Steiner T; Helios Klinikum Erfurt, Erfurt, Germany., Welslau M; Hemato-Oncology Practice, Aschaffenburg Hospital, Aschaffenburg, Germany., Lorch A; Department of Urology, University Hospital Düsseldorf, Düsseldorf, Germany; Department of Medical Oncology and Hematology, University Hospital Zürich, Zürich, Switzerland., Rafiyan R; Clinic for Oncology and Hematology, Krankenhaus Nordwest, Frankfurt, Germany., Hellmis E; Urologicum Duisburg, Duisburg, Germany., Darr C; Clinic for Urology, University Hospital Essen, Essen, Germany., Schütt P; Onkologische Gemeinschaftspraxis, Gütersloh, Germany., Meiler J; Hämatologie/Onkologie, Klinik Dr. Hancken, Stade, Germany., Kretz T; Urologie-Heinsberg, Heinsberg, Germany., Loidl W; Department of Urology and Andrology, Ordensklinikum Linz, Linz, Austria., Flörcken A; Department of Hematology, Oncology and Tumorimmunology, Charité-Universitätsmedizin Berlin, Berlin, Germany., Mänz M; Corbin GmbH, Berlin, Germany., Hinke A; Cancer Clinical Research Consulting, Düsseldorf, Germany., Hartmann A; Institute for Pathology, University Hospital Erlangen, Erlangen, Germany., Grüllich C; Department of Hematology and Oncology, Caritas-Hospital Lebach, Lebach, Germany.
Jazyk: angličtina
Zdroj: European urology [Eur Urol] 2023 Dec; Vol. 84 (6), pp. 571-578. Date of Electronic Publication: 2023 Sep 26.
DOI: 10.1016/j.eururo.2023.09.004
Abstrakt: Background: The role of immune checkpoint inhibitor (ICI) maintenance therapy in metastatic renal cell carcinoma (mRCC) is undefined.
Objective: To determine whether switch maintenance therapy with nivolumab improves clinical outcomes in patients with mRCC with tyrosine kinase inhibitor (TKI) sensitivity.
Design, Setting, and Participants: This open-label phase 2 trial randomized patients with a partial response or stable disease after 10-12-wk TKI induction therapy to either TKI or nivolumab maintenance. Key inclusion criteria were measurable disease, clear cell histology, Eastern Cooperative Oncology Group performance status (ECOG PS) 0-2, and adequate organ function.
Intervention: Intravenous nivolumab 8 × 240 mg every 2 wk, followed by 480 mg every 4 wk or sunitinib 50 mg (4-2 regimen) or pazopanib 800 mg once daily orally.
Outcome Measurements and Statistical Analyses: The primary endpoint was overall survival (OS). Secondary endpoints were the objective response rate (ORR; Response Evaluation Criteria in Solid Tumors v1.1), progression-free survival (PFS), safety (Common Terminology Criteria for Adverse Events v4.03), and patient-reported outcomes (Functional Assessment of Cancer Therapy Kidney Symptom Index). The Kaplan-Meier method, two-sided log-rank tests, and Cox regression models were used for statistical analysis.
Results and Limitations: Maintenance therapy was nivolumab for 25 patients (51.0%) and TKI for 24 (48.9%). The median age was 65 yr (range 35-79). Nine patients (18.4%) were female, 31 (63.3%) had ECOG PS of 0, and 15 (30.6%) had favorable risk. OS data are immature (17 deaths, 34.7%). The ORR was 20.0% (n = 5) for nivolumab and 52.2% (n = 12) for TKI. PFS was worse with nivolumab (hazard ratio 2.57, 95% confidence interval 1.36-4.89; p = 0.003). Grade ≥3 adverse events occurred in 14 patients (56.0%) with nivolumab and 17 (70.8%) with TKI. A major limitation is early termination of our study.
Conclusions: TKI treatment achieved superior ORR and PFS in comparison to nivolumab maintenance therapy. Our data do not indicate a role for nivolumab switch maintenance in mRCC.
Patient Summary: Patients with metastatic kidney cancer who experienced a tumor response or disease stabilization after a short period of targeted treatment with a tyrosine kinase inhibitor did not benefit from a switch to the immunotherapy drug nivolumab. Patients who continued their original treatment achieved better responses and a longer time without disease progression. This trial is registered on EudraCT as 2016-002170-13 and on ClinicalTrials.gov as NCT02959554.
(Copyright © 2023 European Association of Urology. Published by Elsevier B.V. All rights reserved.)
Databáze: MEDLINE
Externí odkaz: