Intracranial response to nivolumab in NSCLC patients with untreated or progressing CNS metastases

Lung Cancer. 2016 Aug:98:114-117. doi: 10.1016/j.lungcan.2016.05.031. Epub 2016 May 31.

Abstract

Central nervous system (CNS) metastases occur in 30% of patients with advanced non-small cell lung cancer (NSCLC). Localized treatments targeting CNS metastases result in delays in systemic therapy administration and are associated with neurocognitive impairment. Nivolumab is an immune check-point inhibitor that is approved as a second-line treatment of NSCLC. Data regarding the intracranial activity of nivolumab is lacking. We retrospectively reviewed the efficacy and safety of nivolumab in five patients with advanced NSCLC and new/progressing intracranial metastases. Intracranial response was assessed by magnetic resonance imaging (MRI) using mRECIST v. 1.1 criteria. All patients had parenchymal brain metastases; two patients had leptomeningeal carcinomatosis diagnosed according to radiological criteria. All patients were asymptomatic and did not require corticosteroids or immediate local therapy. We observed one complete and one partial response in the brain. Stabilization of leptomeningeal carcinomatosis for 10 weeks was achieved in one additional patient. Two patients progressed in the CNS. Time-to-response comprised 5 weeks and 9 weeks; both responses are still ongoing at the time of the report (24+ and 28+ weeks since start of treatment). Systemic responses and intracranial responses were largely concordant. No treatment-related or CNS metastases-related grade≥3 adverse events were observed. Nivolumab might have intracranial activity and favorable safety profile in patients with CNS metastases secondary to NSCLC. Nivolumab CNS activity warrants further evaluation.

Keywords: Brain metastases; Leptomeningeal; Nivolumab; Non-small cell lung cancer; PD-1.

MeSH terms

  • Aged
  • Aged, 80 and over
  • Antibodies, Monoclonal / administration & dosage
  • Antibodies, Monoclonal / adverse effects
  • Antibodies, Monoclonal / therapeutic use*
  • Antineoplastic Agents, Immunological / administration & dosage
  • Antineoplastic Agents, Immunological / adverse effects
  • Antineoplastic Agents, Immunological / therapeutic use*
  • Brain Neoplasms / diagnostic imaging
  • Brain Neoplasms / drug therapy*
  • Brain Neoplasms / secondary*
  • Carcinoma, Non-Small-Cell Lung / pathology*
  • Disease Progression
  • Female
  • Humans
  • Lung Neoplasms / pathology*
  • Magnetic Resonance Imaging
  • Male
  • Middle Aged
  • Nivolumab
  • Positron Emission Tomography Computed Tomography
  • Treatment Outcome

Substances

  • Antibodies, Monoclonal
  • Antineoplastic Agents, Immunological
  • Nivolumab