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Impact of Results of TTF-1 Immunostaining on Efficacy of Platinum-Doublet Chemotherapy in Japanese Patients with Nonsquamous Non-Small-Cell Lung Cancer

Background: Pemetrexed is a key drug in chemotherapy for nonsquamous non-small-cell lung cancer (nonsq NSCLC). Several studies have reported thyroid transcription factor-1 (TTF-1) as a biomarker of the efficacy in chemotherapy regimens, including pemetrexed in non-Asian people.

Objective: We aimed to examine the impact of the results of the TTF-1 immunostaining of tumor cells on the therapeutic effect of chemotherapy in Japanese patients with nonsq NSCLC.

Methods: We examined the results of TTF-1 immunostaining and the clinical background of Japanese patients with nonsq NSCLC who received platinum-doublet chemotherapy at our hospital, from April 2009 to April 2021, and the correlation between regimens with or without pemetrexed in progression-free survival (PFS) and overall survival (OS). The efficacy of each regimen was then compared between TTF-1-positive and TTF-1-negative tumors.

Results: TTF-1 immunostaining was performed in 145 patients during the study period: 92 were positive, and 53 were negative. A total of 24 patients presented with EGFR/ALK gene abnormality (16.6%). The PFS and OS of patients who were TTF-1-positive tended to be longer than those of the patients who were TTF-1-negative under either regimen. In other words, patients who were TTF-1-negative were frequently resistant to numerous chemotherapy drugs and experienced a poor prognosis under both regimens. The OS of patients who were TTF-1-positive and treated with the pemetrexed regimen was significantly longer than those on regimens without pemetrexed (963 vs. 412 days, HR = 0.73; 95% CI 0.55-0.96, p = 0.022), whereas there was no difference in PFS.

Conclusions: The positivity of TTF-1 immunostaining in tumors could be a predominant prognostic marker for patients who have advanced nonsq NSCLC. Our analysis examined the possibility of a pemetrexed regimen leading to a longer prognosis in Asian patients who were TTF-1-positive for nonsq NSCLC, as shown in previous studies.

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