Organ-specific response to nivolumab in patients with non-small cell lung cancer (NSCLC)

Cancer Immunol Immunother. 2018 Dec;67(12):1825-1832. doi: 10.1007/s00262-018-2239-4. Epub 2018 Aug 31.

Abstract

Background: Response to immune checkpoint inhibitors depends on tumor intrinsic properties and also on host factors in the tumour microenvironment including the presence of immune cells (IC). We hypothesized that nivolumab efficacy varies across different metastatic sites.

Methods: We retrospectively analyzed computed tomography scans of patients with metastatic non-small cell lung carcinoma (NSCLC) receiving nivolumab. RECIST 1.1 criteria were applied to assess the overall response rate (ORR) and organ-specific response rate (OSRR).

Results: We analyzed 52 patients including 44% females, 58% adenocarcinoma and 8% never smokers. Involved organs had target-lesions in the lung (42%), liver (25%), lymph nodes (56%) and soft tissue (13%) and non-target lesions in the bones (23%). ORR and disease control rate (DCR) were 20% and 45%, respectively. Median overall survival, progression-free survival and duration of response were 11.9, 2.3 and 10.3 months. OSRR and organ-specific DCR (OSDCR) were 28% and 90% in lymph nodes, 8% and 54 in the liver, and 9% and 55% in lung metastases. Nine out of 12 patients with bone metastases had progressive lesions. The cumulative incidence probability of organ-specific progression at 6 months was 14% in lymph nodes, 42% in the liver, 36% in lung metastases and 26% in the primary tumor, 29% in soft tissue and 33% in adrenal metastases.

Conclusion: In conclusion, the efficacy of immunotherapy is dependent on the metastatic location. Treatment appears more active in lymph nodes compared to other organ sites such as liver, adrenals and bone. Future strategies may include additional local treatment in case of oligoprogression in these organs in patients with otherwise sustained treatment benefit.

Keywords: Checkpoint inhibitors; NSCLC; Organ-specific response; Patterns of response.

MeSH terms

  • Aged
  • Aged, 80 and over
  • Antineoplastic Agents, Immunological / pharmacology
  • Antineoplastic Agents, Immunological / therapeutic use*
  • Carcinoma, Non-Small-Cell Lung / drug therapy*
  • Carcinoma, Non-Small-Cell Lung / immunology
  • Carcinoma, Non-Small-Cell Lung / mortality
  • Carcinoma, Non-Small-Cell Lung / pathology
  • Female
  • Humans
  • Immunomodulation / drug effects*
  • Lung Neoplasms / drug therapy*
  • Lung Neoplasms / immunology
  • Lung Neoplasms / mortality
  • Lung Neoplasms / pathology
  • Male
  • Middle Aged
  • Molecular Targeted Therapy
  • Nivolumab / pharmacology
  • Nivolumab / therapeutic use*
  • Organ Specificity / drug effects
  • Organ Specificity / immunology
  • Retrospective Studies
  • Survival Analysis
  • Treatment Outcome
  • Tumor Microenvironment / drug effects
  • Tumor Microenvironment / immunology

Substances

  • Antineoplastic Agents, Immunological
  • Nivolumab