Cécile Teuma1, Solenne Pelletier2, Mona Amini-Adl3, Marie Perier-Muzet3, Delphine Maucort-Boulch4,5,6,7, Luc Thomas3, Maurice Laville2, Denis Fouque2, Stéphane Dalle3. 1. Department of Nephrology, Centre Hospitalier Lyon Sud, Hospices Civils de Lyon, Université de Lyon, UCBL, INSERM, 165, Chemin du Grand Revoyet, 69495, Pierre Bénite, France. cecile.teuma@hotmail.fr. 2. Department of Nephrology, Centre Hospitalier Lyon Sud, Hospices Civils de Lyon, Université de Lyon, UCBL, INSERM, 165, Chemin du Grand Revoyet, 69495, Pierre Bénite, France. 3. Department of Dermatology, Centre Hospitalier Lyon Sud, Hospices Civils de Lyon, Centre de Recherche en Cancérologie de Lyon, 69495, Pierre Bénite, France. 4. Service de Bio statistique, Hospices Civils de Lyon, Lyon, France. 5. Université de Lyon, Lyon, France. 6. Université Lyon 1, Villeurbanne, France. 7. CNRS UMR5558, Laboratoire de Biométrie et Biologie Evolutive, Equipe Bio Statistique-Santé, Villeurbanne, France.
Abstract
INTRODUCTION: A combined therapy MEK inhibitor, Cobimetinib (CB) and BRAF inhibitor, Vemurafenib (VMF), results in an improvement in progression-free survival among patients with BRAF V600-mutated metastatic melanoma. VMF skin adverse effects attributed to ERK paradoxical activation are decreased by the adjunction of CB. The aim of this study was to determine if this combination also improved the renal side effects of VMF. PATIENTS AND METHODS: To investigate the incidence of acute kidney injury (AKI), we conducted a retrospective observational monocentric study in Lyon Sud University Hospital in France. We included 38 patients with metastatic BRAF-mutated melanomas treated by VMF and CB between March 2015 and June 2016. According to the NCI-CTCAE classification, AKI was defined as an increase in serum creatinine exceeding the baseline concentration by 1.5-fold. Serum creatinine was measured before treatment, then on a monthly basis during treatment, and 1 month after treatment discontinuation. Patients were divided into two main groups: AKI-positive (AKI+) and AKI-negative (AKI-), and further subdivided into three groups according to AKI severity (stage 1-5). RESULTS: Of 38 patients, 29 (76%) were AKI-, and all 9 AKI+ patients (24%) were diagnosed within the first trimester of treatment. Three-quarters of AKI (n = 7, 77%) had stage 1 AKI and the remaining 23% stage 2 AKI. Pre-treatment renal function was significantly better in AKI+ group: 105 vs. 80 ml/min/1.73m² AKI-, p = 0.009. Compared to previous results, the AKI incidence under the combined VMF-CB vs. VMF monotherapy was reduced by 60%. CONCLUSION: We reported a reduced incidence and severity of nephrotoxicity of the association inhibitors of BRAF and MEK compared to a BRAF inhibitor monotherapy.
INTRODUCTION: A combined therapy MEK inhibitor, Cobimetinib (CB) and BRAF inhibitor, Vemurafenib (VMF), results in an improvement in progression-free survival among patients with BRAF V600-mutated metastatic melanoma. VMF skin adverse effects attributed to ERK paradoxical activation are decreased by the adjunction of CB. The aim of this study was to determine if this combination also improved the renal side effects of VMF. PATIENTS AND METHODS: To investigate the incidence of acute kidney injury (AKI), we conducted a retrospective observational monocentric study in Lyon Sud University Hospital in France. We included 38 patients with metastatic BRAF-mutated melanomas treated by VMF and CB between March 2015 and June 2016. According to the NCI-CTCAE classification, AKI was defined as an increase in serum creatinine exceeding the baseline concentration by 1.5-fold. Serum creatinine was measured before treatment, then on a monthly basis during treatment, and 1 month after treatment discontinuation. Patients were divided into two main groups: AKI-positive (AKI+) and AKI-negative (AKI-), and further subdivided into three groups according to AKI severity (stage 1-5). RESULTS: Of 38 patients, 29 (76%) were AKI-, and all 9 AKI+ patients (24%) were diagnosed within the first trimester of treatment. Three-quarters of AKI (n = 7, 77%) had stage 1 AKI and the remaining 23% stage 2 AKI. Pre-treatment renal function was significantly better in AKI+ group: 105 vs. 80 ml/min/1.73m² AKI-, p = 0.009. Compared to previous results, the AKI incidence under the combined VMF-CB vs. VMF monotherapy was reduced by 60%. CONCLUSION: We reported a reduced incidence and severity of nephrotoxicity of the association inhibitors of BRAF and MEK compared to a BRAF inhibitor monotherapy.
Authors: Yuntao Bai; Ji Young Kim; Bijay Bisunke; Laura A Jayne; Josie A Silvaroli; Michael S Balzer; Megha Gandhi; Kevin M Huang; Veronika Sander; Jason Prosek; Rachel E Cianciolo; Sharyn D Baker; Alex Sparreboom; Kenar D Jhaveri; Katalin Susztak; Amandeep Bajwa; Navjot Singh Pabla Journal: Kidney Int Date: 2021-09-15 Impact factor: 18.998
Authors: Harish Seethapathy; Meghan D Lee; Ian A Strohbehn; Orhan Efe; Nifasha Rusibamayila; Donald F Chute; Robert B Colvin; Ivy A Rosales; Riley M Fadden; Kerry L Reynolds; Ryan J Sullivan; Howard L Kaufman; Kenar D Jhaveri; Meghan E Sise Journal: Nephrol Dial Transplant Date: 2022-02-25 Impact factor: 5.992
Authors: Lucie Heinzerling; Thomas K Eigentler; Michael Fluck; Jessica C Hassel; Daniela Heller-Schenck; Jan Leipe; Matthias Pauschinger; Arndt Vogel; Lisa Zimmer; Ralf Gutzmer Journal: ESMO Open Date: 2019-05-23
Authors: Lorenz Thurner; Moritz Bewarder; Florian Rosar; Patrick Orth; Raoul Boris Meuter; Torben Rixecker; Vadim Lesan; Dieter Michael Kohn; Günther Schneider; Daniel Baumhoer; Rainer Maria Bohle; Christian Veith; Joerg Thomas Bittenbring Journal: Hemasphere Date: 2020-12-09