1390P - Clinical characteristics and treatment outcomes of patients with thoracic SMARCA4-deficient tumour

Background

The SMARCA4 gene encodes BRG1, an ATPase subunit of the SWI/SNF complex responsible for chromatin remodeling. The loss of expression of BRG1 is found in 5-10% of non-small cell lung cancers (SD-NSCLC). An undifferentiated SMARCA4-deficient thoracic tumor type (SD-UT) is also described, considered distinct from SD-NSCLC, formerly known as SMARCA4 deficient sarcoma, and reclassified in 2021 (WHO). These two tumor types are rare, with limited data on their clinical, anatomopathological, and biological characteristics.Their prognosis is poor, with low rate of response to chemotherapy. Sensitivity of these tumors to immune checkpoint inhibitors (ICI) remains uncertain.

Methods

We conducted a retrospective multicenter study in France, including patients with SMARCA4-deficient thoracic cancer diagnosed after 2015. Patients were identified based on the loss of BRG1expression in immunohistochemistry (IHC) or the presence of a SMARCA4 mutation.

Results

We included 103 patients from 10 centers, 50 of whom had a SD-UT diagnosis and 53 a SD-NSCLC. 78% were male, with a median age of 61 years and a history of smoking (97%, 35pack-years in median). 70% had a stage IV disease at diagnosis, with a median of 2 metastatic sites. The primary tumor was mostly presenting as a bulky pulmonary mass (median size 57mm). TTF1 IHC was negative in 86% of cases (SD-UT: 94%, SD-NSCLC: 79%). PD-L1expression was unknown, negative, 1-49% and ≥50% in 32%/40%/20%/19%, respectively among SD-UT,and 12%/34%/26%/28% among SD-NSCLC, respectively. Among tumors with molecular analysis available, 84% had a TP53 mutation, 56% STK11 and 25% KRAS. At stage IV disease, median OS was 5.41 and 16.2 months (mo) among SD-UT and SD-NSCLC patients, respectively (HR 0.57; p=0.034). Among patients who received first-line treatment for stage IV disease, median PFS was 5.15 mo with ICI alone or in combination with chemotherapy and 2.82 mo for chemotherapy alone (HR 1.48; p=0.16). It was 2.82 mo in SD-UT and 5.15 mo in SD-NSCLC patients (HR 0.70; p=0.19).

Conclusions

SMARCA4 deficient thoracic tumors have a poor prognosis, especially the undifferentiated subtype. ICI-containing treatment regimens may improve clinical outcomes. Further studies to identify new treatments are needed.

Clinical trial identification

Editorial acknowledgement

Legal entity responsible for the study

The authors.

Funding

ADIR association.

Disclosure

S. Baldacci: Financial Interests, Personal, Invited Speaker: MSD, Boehringer Ingelheim, AstraZeneca; Financial Interests, Personal, Advisory Board: Roche; Other, Support for ESMO congress participation: Pfizer; Other, Support for ELCC congress: Janssen. Y. Oulkhouir: Financial Interests, Personal, Invited Speaker: Amgen. S. Cousin: Financial Interests, Personal, Advisory Board: AbbVie, Amgen, Lilly, Roche; Non-Financial Interests, Principal Investigator: AstraZeneca, Daiichi Sankyo, Gilead, Takeda, Sanofi, MSD, GSK, BMS. P. Fournel: Financial Interests, Personal, Advisory Board: BMS, MSD, Janssen; Financial Interests, Personal, Invited Speaker: AstraZeneca, Amgen, Sanofi; Financial Interests, Personal, Other, Congress invitation: Takeda. N. Piton: Financial Interests, Personal, Financially compensated role: Boehringer Ingelheim; Financial Interests, Advisory Board: BMS, MSD, AstraZeneca. F. Guisier: Financial Interests, Personal, Advisory Board: Amgen, AstraZeneca, BMS, MSD, Roche, Sanofi, Janssen, Pfizer, Takeda; Financial Interests, Institutional, Research Grant: Pfizer, Roche, Takeda. All other authors have declared no conflicts of interest.