Impact of TTF-1 Expression on the Prognostic Prediction of Patients with NSCLC with PD-L1 Expression Levels of 1% to 49%, Treated with Chemotherapy vs Chemoimmunotherapy: A Multicenter, Retrospective Study.

Purpose: Thyroid transcription factor 1 (TTF-1) expression is a useful predictor of treatment efficacy in advanced non-squamous non-small-cell lung cancer (NSCLC). This study aimed to evaluate whether TTF-1 could predict the effectiveness of chemotherapy versus chemoimmunotherapy in patients with non-squamous NSCLC with programmed death ligand-1 (PD-L1) expression between 1% and 49%.

Materials and methods: We conducted a retrospective study of patients with NSCLC who were treated with chemotherapy or chemoimmunotherapy between March 2016 and May 2023. The patients had histologically confirmed NSCLC, stage III-IV or postoperative recurrence, TTF-1 measurements, and PD-L1 expression levels between 1% and 49%. Clinical data were analyzed to evaluate the effect of TTF-1 expression on treatment efficacy.

Results: This study included 283 of 624 patients. TTF-1-positive patients showed longer progression-free survival (PFS) and overall survival (OS) (PFS: 6.4 months [95% confidence interval (CI): 5.0-9.4] vs 4.1 months [95% CI: 2.7-6.1], p=0.03, OS: 17.9 months [95% CI: 15.2-28.1] vs 9.4 months [95% CI: 6.3-17.0], p<0.01) in the chemotherapy cohorts (n=93). In the chemoimmunotherapy cohort (n=190), there was no significant difference in PFS and OS between TTF-1-positive and negative groups (PFS: 7.6 months [95% CI: 6.4-11.0] vs 6.0 months [95% CI: 3.6-12.6], p=0.59, OS: 25.0 months [95% CI: 18.0-49.2] vs 21.3 months [95% CI: 9.8-28.8], p=0.09).

Conclusion: In patients with NSCLC with PD-L1 expression between 1% and 49%, TTF-1 expression was a predictor of chemotherapeutic, but not chemoimmunotherapeutic, efficacy.