Long-term follow up of nivolumab in previously untreated Japanese patients with advanced or recurrent malignant melanoma

Cancer Sci. 2019 Jun;110(6):1995-2003. doi: 10.1111/cas.14015. Epub 2019 May 23.

Abstract

The immune checkpoint inhibitor nivolumab inhibits the programmed death 1 receptor and suppresses the immune resistance of cancer cells. This is a long-term follow up of a single-arm, open-label, multicenter, phase II study of nivolumab in untreated Japanese patients with stage III/IV or recurrent melanoma. In addition, a post-hoc subgroup analysis stratified by melanoma types was performed. Nivolumab was administered intravenously at a dose of 3 mg/kg every 2 weeks. The primary endpoint was the overall response rate (ORR), and secondary endpoints included overall survival (OS), progression-free survival (PFS), best overall response, the disease control rate and change in tumor diameter. Safety was assessed by recording treatment-related adverse events (TRAE), including select immune-related adverse events. Of the 24 patients initially included in the primary phase II study, 10 survived for over 3 years (41.7%). The ORR was 34.8% (90% confidence interval [CI]: 20.8, 51.9) for all patients. When analyzing by melanoma type, the ORR was 66.7% (90% CI: 34.7, 88.3) for superficial spreading, 33.3% (90% CI: 11.7, 65.3) for mucosal, and 28.6% (90% CI: 10.0, 59.1) for acral lentiginous tumors. The median OS was 32.9 months, the 3-year OS rate was 43.5%, and the 3-year PFS rate was 17.2%. A long-term response was observed in all the tumor types. The most common TRAE included skin toxicity (45.8%) and endocrine disorders (29.2%). This study demonstrated the long-term efficacy and tolerability of nivolumab in patients with advanced or recurrent melanoma, irrespective of melanoma type.

Keywords: Japan; clinical efficacy; malignant melanoma; nivolumab; survival rate.

Publication types

  • Clinical Trial, Phase II
  • Multicenter Study

MeSH terms

  • Administration, Intravenous
  • Aged
  • Antineoplastic Agents, Immunological / administration & dosage
  • Antineoplastic Agents, Immunological / therapeutic use
  • Asian People
  • Follow-Up Studies
  • Humans
  • Japan
  • Kaplan-Meier Estimate
  • Male
  • Melanoma / drug therapy*
  • Melanoma / ethnology
  • Melanoma / pathology
  • Melanoma, Cutaneous Malignant
  • Middle Aged
  • Neoplasm Recurrence, Local
  • Nivolumab / administration & dosage
  • Nivolumab / adverse effects
  • Nivolumab / therapeutic use*
  • Pruritus / chemically induced
  • Skin Neoplasms / drug therapy*
  • Skin Neoplasms / ethnology
  • Skin Neoplasms / pathology
  • Vitiligo / chemically induced

Substances

  • Antineoplastic Agents, Immunological
  • Nivolumab