Cancer Chemotherapy and Pharmacology

, Volume 80, Issue 5, pp 999–1004 | Cite as

Efficacy and safety of retreatment with nivolumab in metastatic melanoma patients previously treated with nivolumab

  • Motoo Nomura
  • Atsushi Otsuka
  • Tomohiro Kondo
  • Hiroki Nagai
  • Yumi Nonomura
  • Yo Kaku
  • Shigemi Matsumoto
  • Manabu Muto
Original Article



Nivolumab is a monoclonal antibody directed against programmed death-1 that has been shown to improve survival in patients with metastatic melanoma. However, the efficacy of nivolumab and other agents in melanoma remains limited. The objective of this study was to evaluate the efficacy and safety of retreatment with nivolumab in metastatic melanoma patients who previously progressed on nivolumab.

Patients and methods

A retrospective review was performed on eight consecutive metastatic melanoma patients retreated with nivolumab who progressed on previous nivolumab. These patients received nivolumab 2 mg/kg every 3 weeks. Best responses to each treatment were assessed using RECIST 1.1.


Of eight metastatic melanoma patients, three patients received chemotherapy before first nivolumab. The median first nivolumab treatment period was 4.1 months. During first nivolumab, 3 (37.5%) patients achieved a partial response and 3 (37.5%) patients achieved stable disease as their best response. First nivolumab was discontinued due to disease progression in seven patients and grade 3 colitis in 1 patient. Patients were subsequently treated with ipilimumab (n = 6), vemurafenib (n = 1), or no other medical treatment (n = 1). The median treatment period between first and second nivolumab was 3.0 months. Four patients received radiation therapy between first and second nivolumab. The median second nivolumab treatment period was 4.3 months. Among the eight patients who received second nivolumab, 2 (25%) patients achieved a partial response and 3 (37.5%) patients achieved stable disease as their best response. Second nivolumab was discontinued due to disease progression in seven patients. One patient continues to receive second nivolumab. Among the four patients treated with ipilimumab and radiotherapy between first and second nivolumab, the response rate was 50% and the disease control rate was 75%.


This study showed that retreatment with nivolumab is an option for select metastatic melanoma patients after previous nivolumab treatment.


Metastatic melanoma Chemotherapy Immune checkpoint inhibitor 


Compliance with ethical standards


None of the authors have financial disclosures or funding support.

Ethical approval

All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards.

Conflict of interest

None of the authors have conflicts of interest to declare.

Informed consent

Informed consent was obtained from all individual participants included in the study.


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Copyright information

© Springer-Verlag GmbH Germany 2017

Authors and Affiliations

  1. 1.Department of Therapeutic OncologyKyoto University Graduate School of MedicineKyotoJapan
  2. 2.Department of DermatologyKyoto University Graduate School of MedicineKyotoJapan
  3. 3.Translational Research Department for Skin and Brain DiseasesKyoto University Graduate School of MedicineKyotoJapan

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