Role of immunotherapy in stage III nonsmall cell lung cancer

Curr Opin Oncol. 2019 Jan;31(1):18-23. doi: 10.1097/CCO.0000000000000493.

Abstract

Purpose of review: Despite aggressive treatment based on definitive chemoradiotherapy, 5-year overall survival in unresectable stage III nonsmall cell lung cancer remains poor (15-20%). The novel immunotherapy based on immune checkpoint inhibitors (ICIs) presents as the therapeutic 'Holly Grail' in lung cancer treatment.

Recent findings: Preclinical models provide evidence of immunotherapy-radiotherapy (IM-RT) synergy. The exposure to ionizing radiation turns tumor in an in-situ vaccine, primes the innate immune system, increases immunotherapy efficacy by overcoming the immunosuppressive microenvironment of immune-resistant tumors and promotes a systemic, out-of-field antitumor T-cell-mediated response called abscopal effect. The immunomodulatory and abscopal effects of radiotherapy can be further enhanced by combining with systemic immunotherapies. The phase III START trial proved that liposomal vaccine - tecemotide (L-BLP25) administered as maintenance therapy after concurrent chemoradiotherapy (CRT) in LA-NSCLC prolongs survival. In the phase III PACIFIC trial consolidation with durvalumab, an anti-PDL-1 antibody, was associated with survival benefit in patients diagnosed with LA-NSCLC who responded to concurrent chemoradiotherapy.

Summary: PACIFIC trial results are expected to definitely establish durvalumab as standard consolidation strategy in LA-NSCLC. Many clinical trials are ongoing in the field of immunoradiotherapy in LA-NSCLC to define the optimal conditions for this therapeutic combination.

Publication types

  • Review

MeSH terms

  • Antibodies, Monoclonal / administration & dosage
  • Cancer Vaccines / administration & dosage
  • Carcinoma, Non-Small-Cell Lung / immunology
  • Carcinoma, Non-Small-Cell Lung / pathology
  • Carcinoma, Non-Small-Cell Lung / radiotherapy*
  • Carcinoma, Non-Small-Cell Lung / therapy*
  • Clinical Trials, Phase III as Topic
  • Combined Modality Therapy
  • Humans
  • Immunotherapy / methods*
  • Lung Neoplasms / immunology
  • Lung Neoplasms / pathology
  • Lung Neoplasms / radiotherapy*
  • Lung Neoplasms / therapy*
  • Neoplasm Staging
  • Randomized Controlled Trials as Topic

Substances

  • Antibodies, Monoclonal
  • Cancer Vaccines
  • durvalumab