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Successful treatment with sintilimab for SMARCA4-deficient non-small cell lung carcinoma: two case reports

Liwen Wang1,2, Hua Ke3, Chengdi Wang4

  • 1Department of Pulmonary and Critical Care Medicine, West China Hospital, Sichuan University, Chengdu, Sichuan, China.

Discover Oncology
|July 1, 2025
PubMed

Insights

SMARCA4-deficient non-small cell lung cancer (NSCLC) is aggressive. Two patients showed significant benefit from immune checkpoint inhibitors (ICIs), suggesting this therapy may improve survival for this NSCLC subtype.

Area of Science:

  • Oncology
  • Molecular Biology
  • Genetics

Background:

  • SMARCA4 is a key component of the SWI/SNF chromatin-remodeling complex, involved in transcriptional regulation and acting as a tumor suppressor.
  • Loss or mutation of SMARCA4 occurs in approximately 8% of non-small cell lung carcinomas (NSCLCs), leading to a highly aggressive subtype (SMARCA4-dNSCLC).
  • SMARCA4-deficient NSCLC (SMARCA4-dNSCLC) exhibits poor prognosis with short overall survival (OS) and limited response to conventional chemotherapy.

Purpose of the Study:

  • To investigate the efficacy of immune checkpoint inhibitors (ICIs) in patients with SMARCA4-deficient non-small cell lung cancer (NSCLC).
  • To present clinical case studies of SMARCA4-dNSCLC patients treated with ICIs.

Main Methods:

  • Case report of two patients diagnosed with SMARCA4-deficient non-small cell lung cancer (NSCLC).
  • Treatment administered included immune checkpoint inhibitors (ICIs), potentially in combination with chemotherapy.
  • Clinical outcomes, including progression-free survival (PFS) and overall survival (OS), were monitored.

Main Results:

  • Both reported patients with SMARCA4-dNSCLC experienced substantial clinical benefits from ICI treatment.
  • Prolonged progression-free survival (PFS) was observed in these patients.
  • The findings suggest a positive response to immunotherapy in this aggressive NSCLC subtype.

Conclusions:

  • Immune checkpoint inhibitors (ICIs) show promise as a therapeutic strategy for SMARCA4-deficient non-small cell lung cancer (NSCLC).
  • Combination therapy with ICIs and chemotherapy may offer a viable treatment option for SMARCA4-dNSCLC.
  • Early implementation of ICI-based therapy following diagnosis could potentially improve survival outcomes for patients with SMARCA4-dNSCLC.
Keywords:
ChemotherapyImmune checkpoint inhibitorNon-small cell lung carcinomaSMARCA4Sintilimab

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