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Adjunction of a MEK inhibitor to Vemurafenib in the treatment of metastatic melanoma results in a 60% reduction of acute kidney injury

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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.

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Acknowledgements

The authors would like to thank the members of Dermatology Department of the CHU Lyon Sud, Mathilde Nouvier MD, Pierre Trolliet and Louis De Laforcade MD from the Nephrology Department of CHU Lyon Sud, Lyon, France for the help with patient recruitment.

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Authors and Affiliations

  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

    Cécile Teuma, Solenne Pelletier, Maurice Laville & Denis Fouque

  2. Department of Dermatology, Centre Hospitalier Lyon Sud, Hospices Civils de Lyon, Centre de Recherche en Cancérologie de Lyon, 69495, Pierre Bénite, France

    Mona Amini-Adl, Marie Perier-Muzet, Luc Thomas & Stéphane Dalle

  3. Service de Bio statistique, Hospices Civils de Lyon, Lyon, France

    Delphine Maucort-Boulch

  4. Université de Lyon, Lyon, France

    Delphine Maucort-Boulch

  5. Université Lyon 1, Villeurbanne, France

    Delphine Maucort-Boulch

  6. CNRS UMR5558, Laboratoire de Biométrie et Biologie Evolutive, Equipe Bio Statistique-Santé, Villeurbanne, France

    Delphine Maucort-Boulch

Authors
  1. Cécile Teuma
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  2. Solenne Pelletier
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  3. Mona Amini-Adl
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  4. Marie Perier-Muzet
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  5. Delphine Maucort-Boulch
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  6. Luc Thomas
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  7. Maurice Laville
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  8. Denis Fouque
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  9. Stéphane Dalle
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Corresponding author

Correspondence to Cécile Teuma.

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The authors declare that they have no conflict of interest.

Ethical standards

All procedures in our study involving human participants were in accordance with the ethical standards with the 1964 Helsinki declaration and its later amendments or comparable ethical standards.

Animal rights

This article does not contain any studies with animals performed by any of the authors.

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Teuma, C., Pelletier, S., Amini-Adl, M. et al. Adjunction of a MEK inhibitor to Vemurafenib in the treatment of metastatic melanoma results in a 60% reduction of acute kidney injury. Cancer Chemother Pharmacol 79, 1043–1049 (2017). https://doi.org/10.1007/s00280-017-3300-2

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  • DOI: https://doi.org/10.1007/s00280-017-3300-2

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