Clinical parameters associated with anti-programmed death-1 (PD-1) inhibitors-induced tumor response in melanoma patients

Invest New Drugs. 2017 Dec;35(6):842-847. doi: 10.1007/s10637-017-0476-6. Epub 2017 May 31.

Abstract

Background The identification of the melanoma patients sensitive to anti-PD-1 inhibitors, nivolumab or pembrolizumab, is a major therapeutic challenge and an urgent need. We hypothesized that the natural history of the disease might partly reflect the immune state of the patients. Methods We analyzed our cohort of melanoma patients treated with anti-PD-1 from August 2014 to January 2016 in our institution. Objective response was defined as a complete or partial response according to v1.1 RECIST criteria. Results Among 63 metastatic melanoma patients, the overall response rate was 43%. Median time from diagnosis to anti-PD-1 initiation was longer among responders than non-responders (64 months vs. 35 months, p = 0.02). The response rate was 10% in patients starting anti-PD-1 within 1 year, 35% after 1 to 5 years and 63% after 5 years. Performance status (PS) 0 was also associated with enhanced tumor response: 70% of responders were PS 0 vs. 36% of non-responders (p = 0.04). PS 0, normal LDH levels and wild-type BRAF status were significant predictors of progression free survival. Conclusion A long time lapse from diagnosis to anti-PD-1 initiation and PS 0 are associated with higher sensitivity to anti-PD-1 in melanoma patients. These two clinical features might reflect a potentially intact immune system of the host.

Keywords: Disease kinetics; Dissemination; Melanoma; Nivolumab; Pembrolizumab; Prognostic factors.

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Antibodies, Monoclonal / administration & dosage
  • Antibodies, Monoclonal, Humanized / administration & dosage
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use*
  • Brain Neoplasms / drug therapy
  • Brain Neoplasms / secondary*
  • Female
  • Follow-Up Studies
  • Humans
  • Lymphatic Metastasis
  • Male
  • Melanoma / drug therapy
  • Melanoma / pathology*
  • Middle Aged
  • Neoplasm Invasiveness
  • Neoplasm Recurrence, Local / drug therapy
  • Neoplasm Recurrence, Local / pathology*
  • Nivolumab
  • Prognosis
  • Programmed Cell Death 1 Receptor / antagonists & inhibitors*
  • Retrospective Studies
  • Survival Rate
  • Young Adult

Substances

  • Antibodies, Monoclonal
  • Antibodies, Monoclonal, Humanized
  • PDCD1 protein, human
  • Programmed Cell Death 1 Receptor
  • Nivolumab
  • pembrolizumab