Safety and Antitumor Activity of Anti-PD-1 Antibody, Nivolumab, in Patients With Platinum-Resistant Ovarian Cancer

J Clin Oncol. 2015 Dec 1;33(34):4015-22. doi: 10.1200/JCO.2015.62.3397. Epub 2015 Sep 8.

Abstract

Purpose: Programmed death-1 (PD-1), a coinhibitory immune signal receptor expressed in T cells, binds to PD-1 ligand and regulates antitumor immunity. Nivolumab is an anti-PD-1 antibody that blocks PD-1 signaling. We assessed the safety and antitumor activity of nivolumab in patients with platinum-resistant ovarian cancer.

Patients and methods: Twenty patients with platinum-resistant ovarian cancer were treated with an intravenous infusion of nivolumab every 2 weeks at a dose of 1 or 3 mg/kg (constituting two 10-patient cohorts) from October 21, 2011. This phase II trial defined the primary end point as the best overall response. Patients received up to six cycles (four doses per cycle) of nivolumab treatment or received doses until disease progression occurred. Twenty nivolumab-treated patients were evaluated at the end of the trial on December 7, 2014.

Results: Grade 3 or 4 treatment-related adverse events occurred in eight (40%) of 20 patients. Two patients had severe adverse events. In the 20 patients in whom responses could be evaluated, the best overall response was 15%, which included two patients who had a durable complete response (in the 3-mg/kg cohort). The disease control rate in all 20 patients was 45%. The median progression-free survival time was 3.5 months (95% CI, 1.7 to 3.9 months), and the median overall survival time was 20.0 months (95% CI, 7.0 months to not reached) at study termination.

Conclusion: This study, to our knowledge, is the first to explore the effects of nivolumab against ovarian cancer. The encouraging safety and clinical efficacy of nivolumab in patients with platinum-resistant ovarian cancer indicate the merit of additional large-scale investigations (UMIN Clinical Trials Registry UMIN000005714).

Publication types

  • Clinical Trial, Phase II
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenocarcinoma, Clear Cell / drug therapy
  • Adenocarcinoma, Clear Cell / mortality
  • Adenocarcinoma, Clear Cell / secondary
  • Aged
  • Antibodies, Monoclonal / therapeutic use*
  • Antineoplastic Agents / therapeutic use*
  • Cohort Studies
  • Cystadenocarcinoma, Serous / drug therapy
  • Cystadenocarcinoma, Serous / mortality
  • Cystadenocarcinoma, Serous / secondary
  • Drug Resistance, Neoplasm / drug effects*
  • Endometrial Neoplasms / drug therapy
  • Endometrial Neoplasms / mortality
  • Endometrial Neoplasms / secondary
  • Female
  • Follow-Up Studies
  • Humans
  • Lymphatic Metastasis
  • Middle Aged
  • Neoplasm Invasiveness
  • Neoplasm Recurrence, Local / drug therapy*
  • Neoplasm Recurrence, Local / mortality
  • Neoplasm Recurrence, Local / pathology
  • Neoplasm Staging
  • Nivolumab
  • Ovarian Neoplasms / drug therapy*
  • Ovarian Neoplasms / mortality
  • Ovarian Neoplasms / pathology
  • Peritoneal Neoplasms / drug therapy
  • Peritoneal Neoplasms / mortality
  • Peritoneal Neoplasms / secondary
  • Platinum / pharmacology
  • Prognosis
  • Programmed Cell Death 1 Receptor / antagonists & inhibitors*
  • Programmed Cell Death 1 Receptor / immunology
  • Salvage Therapy*
  • Survival Rate

Substances

  • Antibodies, Monoclonal
  • Antineoplastic Agents
  • PDCD1 protein, human
  • Programmed Cell Death 1 Receptor
  • Nivolumab
  • Platinum

Associated data

  • JPRN/UMIN000005714