Abstract 434P
Background
SMARCA4-deficient undifferentiated thoracic tumors (UT) are a recently recognized and highly aggressive group of cancers. The effectiveness of standard treatments for these tumors, which share similarities with non-small cell lung cancer (NSCLC), remains uncertain. In this study, we analyse ten cases of SMARCA4-deficient UT to explore the clinical and pathological features and outcomes associated with these tumors.
Methods
We collected clinical and demographic information from ten patients whose tumors met the criteria for SMARCA4-deficient UT. These criteria, outlined in the 2021 WHO Classification of Thoracic Tumors (5th Edition), included undifferentiated tumor morphology and the loss of SMARCA4/BRG1 expression, as determined by immunohistochemistry.
Results
We identified 10 patients with a median age of 61 years (46–79). Among them, 7 were male and 3 were females. 2 patient was a non-smoker, while the other 8 were smokers (median 40 pack years). All 10 patients were diagnosed at stage IV. PD-L1 testing revealed that 4 had high expression (>50%), while 2 were negative. Median Tumor mutational burden (TMB) value was 10.5 mutations/Mb (7.6–34). Next-generation sequencing results showed mutations in SMARCA4 (100%), TP53 (60%), and KRAS (20%). In these patients, first-line systemic treatments were implemented, with the majority (n=7) receiving a combination chemo-immunotherapy. The median progression-free survival (PFS) was 2.7 months. Those who received immunotherapy exhibited a slightly better median PFS of 3.6 months compared to 1.5 months for chemotherapy alone. The median overall survival was 7.7 months. 1 patient experienced durable response lasting over 1 year who received combination chemo-immunotherapy, had high PD-L1 expression with TMB of 24 mutations/Mb.
Conclusions
SMARCA4-deficient undifferentiated thoracic tumors represent a highly aggressive cancer with poor outcomes when treated with standard therapies. However, a small subset responds well to immunotherapies. Clinicians should be aware of the rapid disease progression and consider enrolling patients in clinical trials for novel treatments as early as possible.
Legal entity responsible for the study
The authors.
Funding
Has not received any funding.
Disclosure
All authors have declared no conflicts of interest.