Diffuse and Strong TTF-1 Expression Predicts Response to Pemetrexed-Based Immunochemotherapy in Advanced Lung...

Area of Science:

• Oncology
• Immunotherapy
• Molecular Diagnostics

Background:

• Thyroid Transcription Factor-1 (TTF-1) is recognized as a prognostic marker in non-small cell lung carcinoma (NSCLC).
• The precise threshold of TTF-1 expression needed to predict immunochemotherapy response remains undefined.
• Evaluating TTF-1 as a predictive biomarker for targeted therapies in NSCLC is crucial.

Purpose of the Study:

• To determine the optimal cut-off for TTF-1 expression (considering both staining intensity and percentage of positive cells) as a predictive factor for immunochemotherapy response in NSCLC.
• To investigate the correlation between TTF-1 expression levels and treatment outcomes, specifically progression-free survival (PFS).
• To assess the utility of TTF-1 in stratifying patients for pemetrexed-based immunochemotherapy.

Main Methods:

• A retrospective multicenter study involving 95 patients with advanced lung adenocarcinoma or NSCLC with adenocarcinoma features treated with immunochemotherapy.
• Centralized immunohistochemical analysis of TTF-1 expression using the 8G7G3/1 antibody, with scoring based on staining intensity and ratio (0-5).
• Statistical analysis to compare PFS between different TTF-1 expression levels and treatment regimens, including multivariate analysis.

Main Results:

• A TTF-1 score of ≥5 (indicating diffuse and strong staining) was identified as a positive predictive factor, observed in 61.1% of patients.
• Patients with TTF-1 positivity showed significantly longer PFS compared to TTF-1 negative patients when treated with pemetrexed-based immunochemotherapy (HR: 0.51).
• TTF-1 negativity was associated with a higher proportion of programmed death ligand 1 (PD-L1) tumor proportion score (TPS) <1%.

Conclusions:

• Diffuse and strong TTF-1 positivity (score ≥5) is a significant predictive factor for favorable outcomes in patients with lung adenocarcinoma receiving pemetrexed-based immunochemotherapy.
• TTF-1 expression analysis holds potential for developing more personalized and effective immunochemotherapy strategies for lung adenocarcinoma.
• Further research into TTF-1 as a biomarker may refine treatment selection and improve patient prognosis in NSCLC.