Clinical factors associated with early progression and grade 3-4 toxicity in patients with advanced non-small-cell lung cancers treated with nivolumab

PLoS One. 2018 Apr 23;13(4):e0195945. doi: 10.1371/journal.pone.0195945. eCollection 2018.

Abstract

Introduction: The prognosis of advanced non-small-cell lung cancer (NSCLC) has been improved by development of immune checkpoint inhibitors (ICIs) such as nivolumab for second-line treatment. As phase III trials include only selected patients, we here investigated the clinical factors associated with efficacy and safety of nivolumab in 'real life' patients with advanced NSCLC.

Methods: Clinical and histological characteristics, therapies and survival data of all consecutive patients with advanced NSCLC included prospectively and treated by nivolumab in two French academic hospitals between February 2015 and December 2016 were examined.

Results: Sixty-seven patients were included, mostly male (69%), current or former smokers (87%) with PS <2 (73%). Median age was 68.5 years and 42% were aged ≥70 years. According to uni- and multi-variate analyses, only PS 2 (OR = 0.17, 95% CI 0.03-0.99, p = 0.049) and number of previous treatment lines (OR = 0.33, 95% CI 0.13-0.85, p = 0.022) were significantly negatively associated with tumor control. Worse progression-free survival (PFS) was significantly associated with PS 2 (HR = 5.17, 95% CI 1.99-13.43, p = 0.001) and use of steroids (HR = 3.27, 95% CI 1.39-7.69, p = 0.006). Worse overall survival was associated with symptomatic brain metastasis (HR = 3.15, 95% CI 1.23-8.85, p = 0.029). Treatment-related adverse events occurred in 47 patients (70%), symptomatic brain metastasis being significantly associated with Grade ≥3 toxicity (OR = 8.13, 95% CI 1.21-55.56, p = 0.031). Age and nutritional status were not associated with response, PFS, OS or toxicity.

Conclusion: Our results suggest that nivolumab is not beneficial or safe for patients with PS 2 and symptomatic brain metastases.

Publication types

  • Clinical Trial, Phase III

MeSH terms

  • Aged
  • Antibodies, Monoclonal / administration & dosage*
  • Antibodies, Monoclonal / adverse effects
  • Antineoplastic Agents / administration & dosage*
  • Antineoplastic Agents / adverse effects
  • Carcinoma, Non-Small-Cell Lung / drug therapy*
  • Disease Progression
  • Female
  • Humans
  • Lung Neoplasms / drug therapy*
  • Male
  • Middle Aged
  • Nivolumab
  • Prospective Studies
  • Survival Analysis
  • Treatment Outcome

Substances

  • Antibodies, Monoclonal
  • Antineoplastic Agents
  • Nivolumab

Grants and funding

The authors received no specific funding for this work.