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Published on: April 22, 2019
Efficacy of Immune Checkpoint Inhibitors in SMARCA4-Deficient Thoracic Tumor
Yuki Shinno1, Akihiko Yoshida2, Ken Masuda1
1Department of Thoracic Oncology, National Cancer Center Hospital, Tokyo, Japan.
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.
Insights
Immune checkpoint inhibitors targeting programmed death 1 (PD-1) or programmed death ligand 1 (PD-L1) show promise for SMARCA4-deficient thoracic tumors. First-line therapy demonstrated better outcomes, suggesting potential benefit for these rare cancers.
Area of Science:
- Oncology
- Genetics
- Immunotherapy
Background:
- SMARCA4-deficient thoracic tumors are a distinct entity arising from SMARCA4 gene mutations leading to protein loss.
- These tumors present with diverse phenotypes, including carcinomatous and sarcomatoid types.
- The efficacy of programmed death 1 (PD-1) and programmed death ligand 1 (PD-L1) inhibitors in this patient group is not well-established.
Purpose of the Study:
- To evaluate the clinical outcomes of patients with SMARCA4-deficient thoracic tumors treated with immune checkpoint inhibitors (ICIs).
- To assess the response rates and survival data for patients receiving PD-1/PD-L1 inhibitors.
- To explore the potential benefit of ICIs in this rare thoracic malignancy.
Main Methods:
- Retrospective analysis of SMARCA4-deficient thoracic tumor cases from a national cancer center.
- Review of clinical data for patients treated with PD-1/PD-L1 inhibitors.
- Categorization of tumors into carcinoma, sarcomatoid, and ambiguous types.
Main Results:
- Eighteen patients were identified, with 12 receiving ICIs.
- Five patients (42%) achieved a partial response, notably those treated with first-line ICIs.
- Median progression-free survival was 2.4 months overall, but not reached for patients receiving first-line ICIs.
Conclusions:
- Programmed death 1 (PD-1)/programmed death ligand 1 (PD-L1) inhibitors demonstrate encouraging efficacy in SMARCA4-deficient thoracic tumors.
- First-line immunotherapy appears to yield superior outcomes.
- Further research is warranted for optimal patient selection and combination therapies.
