Everolimus after failure of one prior VEGF-targeted therapy in metastatic renal cell carcinoma: Final results of the MARC-2 trial.

MARC-2, a prospective, multicenter phase IV trial, aimed to investigate clinical outcomes in patients with metastatic renal cell carcinoma (mRCC) treated with everolimus after failure of one initial vascular endothelial growth factor receptor tyrosine kinase inhibitor (VEGFR-TKI) therapy and to identify subgroups benefiting most, based on clinical characteristics and biomarkers.

Patients with clear cell mRCC failing one initial VEGFR-TKI received everolimus until progression or unacceptable toxicity. Primary endpoint was 6-month progression-free survival rate (6moPFS). Secondary endpoints were overall response rate (ORR), PFS, overall survival (OS) and safety. Between 2011-2015, 63 patients were enrolled. Median age was 65.4 years (range 43.3-81.1). 6moPFS was 39.3% (95%-confidence interval [CI] 27.0-51.3) overall, 54.4% (95%-CI 35.2-70.1) vs 23.7% (95%-CI 10.5-39.9) for patients aged ≥65 years vs <65 years, and 51.4% (95%-CI 34.7-65.7) vs 18.2% (95%-CI 5.7-36.3) for patients with body mass index (BMI) >25kg/m2 vs ≤25kg/m2 . A Cox proportional hazards model confirmed a longer PFS for patients aged ≥65 years (Hazard Ratio [HR] 0.46, 95% CI 0.26-0.80) and a longer OS for patients with BMI >25kg/m2 (HR 0.36, 95% CI 0.18-0.71). Median PFS and median OS were 3.8 months (95%-CI 3.2-6.2) and 16.8 months (95%-CI 14.3-24.3). ORR was 7.9%, disease control rate 60.3%. No new safety signals emerged. Most common adverse events were stomatitis (31.7%), fatigue (31.7%) and anemia (30.2%). One patient died from treatment-related upper gastrointestinal hemorrhage. Everolimus remains a safe and effective treatment option for mRCC patients after one prior VEGFR-TKI therapy. Patients aged ≥65 years and patients with BMI >25kg/m2 benefited most.

International journal of cancer. 2020 Oct 18 [Epub ahead of print]

Michael Staehler, Michael Stöckle, Daniel C Christoph, Arnulf Stenzl, Karin Potthoff, Marc-Oliver Grimm, Dunja Klein, Johanna Harde, Fabian Brüning, Peter J Goebell, Marinela Augustin, Frederik Roos, Iris Benz-Rüd, Norbert Marschner, Viktor Grünwald

Department of Urology, Interdisciplinary Center of Renal Tumors, Ludwig-Maximilians-University of Munich, Munich, Germany., Department of Urology and Paediatric Urology, Saarland University Medical Center, Homburg, Germany., Department of Medical Oncology, University Hospital Essen, Essen, Germany., Department of Urology, University Hospital Tuebingen, Tübingen, Germany., OMEDICO, Medical Department, Freiburg im Breisgau, Germany., Department of Urology, University Hospital Jena, Jena, Germany., iOMEDICO, Biostatistics, Freiburg im Breisgau, Germany., Department of Urology and Pediatric Urology, Baldingerstrasse, Philipps-University Marburg, University Hospital Giessen and Marburg GmbH, Marburg, Germany., Ambulatory Uro-Oncological Therapy Unit Erlangen (AURONTE), Department of Urology and Clinic for Haematology and Internistic Oncology, University Hospital Erlangen, Erlangen, Germany., Department of Hematology and Oncology, Klinikum Nuremberg, Paracelsus Medical University, Nürnberg, Germany., Department of Urology, University Hospital Frankfurt, Frankfurt, Germany., Outpatient-Centre for Interdisciplinary Oncology and Haematology, Freiburg, Germany., Department of Hematology, Hemostasis, Oncology and Stem Cell Transplantation, University Hospital Hannover Medical School, Hannover, Germany.