Efficacy of Immune Checkpoint Inhibitors in SMARCA4-Deficient Thoracic Tumor

Clin Lung Cancer. 2022 Jul;23(5):386-392. doi: 10.1016/j.cllc.2022.03.005. Epub 2022 Apr 29.


Background: SMARCA4-deficient thoracic tumor is a novel disease entity characterized by mutations in SMARCA4 resulting in loss of its expression. They could be divided according to their phenotypes; carcinoma or sarcomatoid. It remains unclear how many patients with these SMARCA4-deficient tumors could benefit from inhibitors of programmed death 1 (PD-1) or programmed death ligand 1 (PD-L1).

Methods: SMARCA4-deficient thoracic tumor cases were retrospectively identified from pathology and gene expression databases at the National Cancer Center Hospital in Japan. Clinical outcomes of patients treated with PD-1/PD-L1 inhibitors were reviewed.

Results: Eighteen patients with SMARCA4-deficient thoracic tumor [carcinoma (n = 10), sarcomatoid (n = 7), and ambiguous type (n = 1)] were identified. Of the twelve [carcinoma (n = 7), sarcomatoid (n = 5)] who had received immune checkpoint inhibitors (ICIs), 5 [carcinoma (n = 3), sarcomatoid (n = 2)] showed a partial response, all of whom had received an ICI as the first-line therapy. The overall response rate was The PD-L1 tumor proportion scores of the 5 responding patients were 100%, 80%, 5% (n = 2), and less than 1%. The median progression-free survival (PFS) of all the patients was 2.4 months [95% confidence interval (CI), 1.1 months-not achieved (NA)], while the median PFS of the 3 patients who received first-line ICIs was not reached (95% CI, 1.1 months-NA).

Conclusion: PD-1/PD-L1 inhibitors showed promising results in the treatment of SMARCA4-deficient tumor. Further studies, especially on patient selection and combination therapy, are needed.

Keywords: Immunotherapy; Lung cancer; PD-1/PD-L1; SMARCA4; Switch/sucrose-non-fermentable (SWI/SNF).

MeSH terms

  • Antineoplastic Agents, Immunological* / therapeutic use
  • B7-H1 Antigen / genetics
  • B7-H1 Antigen / metabolism
  • Biomarkers, Tumor / genetics
  • Carcinoma*
  • Carcinoma, Non-Small-Cell Lung* / drug therapy
  • DNA Helicases / genetics
  • Humans
  • Immune Checkpoint Inhibitors / therapeutic use
  • Lung Neoplasms* / drug therapy
  • Lung Neoplasms* / genetics
  • Lung Neoplasms* / pathology
  • Nuclear Proteins / genetics
  • Programmed Cell Death 1 Receptor
  • Retrospective Studies
  • Thoracic Neoplasms* / drug therapy
  • Thoracic Neoplasms* / genetics
  • Transcription Factors / genetics


  • Antineoplastic Agents, Immunological
  • B7-H1 Antigen
  • Biomarkers, Tumor
  • Immune Checkpoint Inhibitors
  • Nuclear Proteins
  • Programmed Cell Death 1 Receptor
  • Transcription Factors
  • SMARCA4 protein, human
  • DNA Helicases