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Published on: February 8, 2018
TTF-1 expression stratifies chemoimmunotherapy benefits in PD-L1-negative lung adenocarcinoma: a real-world biomarker
Ning Yang1, Lijuan Xiong2, Ya Guo3,4
1Department of Oncology, General Hospital of Southern Theater Command, Guangzhou, China.
Background:
The efficacy of immunotherapy in programmed death-ligand 1 (PD-L1)-negative advanced lung adenocarcinoma remains controversial, with responsive subgroups poorly characterized. This study aimed to identify predictive subgroups through thyroid transcription factor-1 (TTF-1) expression stratification.
Methods:
We retrospectively analyzed 253 consecutive PD-L1-negative advanced lung adenocarcinoma patients treated between January 2018 and January 2024. Outcomes of TTF-1-positive and TTF-1-negative patients receiving chemoimmunotherapy vs. chemotherapy alone were compared. Cox multivariate analysis evaluated the prognostic impact of treatment regimens.
Results:
In the overall cohort, chemoimmunotherapy improved median progression-free survival [PFS: 7.9 vs. 6.6 months, hazard ratio (HR) =0.74, P=0.03] and overall survival (OS: 17.5 vs. 15.4 months, HR =0.69, P=0.02) compared to chemotherapy. Stratified by TTF-1 status, TTF-1-negative patients (n=66) receiving chemoimmunotherapy exhibited significantly superior PFS (7.5 vs. 4.8 months, HR =0.44, P=0.002) and OS (16.2 vs. 11.5 months, HR =0.44, P=0.005), whereas TTF-1-positive patients (n=187) showed no significant survival differences (PFS: 8.0 vs. 7.3 months, HR =0.88, P=0.42; OS: 18.7 vs. 18.3 months, HR= 0.86, P=0.44). Multivariate analysis confirmed chemoimmunotherapy as an independent favorable prognostic factor for TTF-1-negative patients [PFS: adjusted HR (aHR) =0.44, 95% confidence interval (CI): 0.24-0.81, P=0.008; OS: aHR =0.48, 95% CI: 0.25-0.90, P=0.02], but demonstrated no significant association in the TTF-1-positive cohort (PFS: aHR =0.93, 95% CI: 0.68-1.28, P=0.66; OS: aHR =0.91, 95% CI: 0.62-1.35, P=0.64).
Conclusions:
TTF-1 expression may be a useful predictive biomarker for chemoimmunotherapy benefit in PD-L1-negative lung adenocarcinoma, pending further validation. TTF-1-negative patients demonstrated improved survival with chemoimmunotherapy (especially taxane-based regimens) compared to chemotherapy alone, while TTF-1-positive patients showed no survival benefit from immunotherapy combinations.
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