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. 2022 Nov;11(11):2208-2215.
doi: 10.21037/tlcr-22-393.

Association of thyroid transcription factor-1 (TTF-1) expression with efficacy of PD-1/PD-L1 inhibitors plus pemetrexed and platinum chemotherapy in advanced non-squamous non-small cell lung cancer

Ritsu Ibusuki #  1 , Yasuto Yoneshima #  1 , Mikiko Hashisako  2 , Norikazu Matsuo  3 , Taishi Harada  4 , Yuko Tsuchiya-Kawano  5 , Junji Kishimoto  6 , Keiichi Ota  1 , Yoshimasa Shiraishi  1 , Eiji Iwama  1 , Kentaro Tanaka  1 , Yoshinao Oda  2 , Isamu Okamoto  1
Affiliations

Association of thyroid transcription factor-1 (TTF-1) expression with efficacy of PD-1/PD-L1 inhibitors plus pemetrexed and platinum chemotherapy in advanced non-squamous non-small cell lung cancer

Ritsu Ibusuki et al. Transl Lung Cancer Res. 2022 Nov.

Abstract

Background: Thyroid transcription factor-1 (TTF-1) expression in advanced non-squamous non-small cell lung cancer (NSCLC) has been associated with the efficacy of pemetrexed plus platinum chemotherapy. However, the relation between TTF-1 expression and efficacy of the combination of programmed cell death 1 (PD-1)/programmed cell death ligand 1 (PD-L1) inhibitors plus pemetrexed and platinum chemotherapy, a standard first-line treatment regimen for advanced non-squamous NSCLC, has remained unclear.

Methods: We retrospectively evaluated TTF-1 expression in tumor tissue of patients with advanced or recurrent non-squamous NSCLC treated with PD-1/PD-L1 inhibitors plus pemetrexed and platinum chemotherapy in the first-line setting. Clinical characteristics and pathological data for each patient were assessed, and progression-free survival (PFS) was evaluated. Bias due to patient background was minimized by application of inverse probability of treatment weighting (IPTW) analysis.

Results: A total of 122 patients, 75 (61.5%) of whom were positive for TTF-1 immunostaining in tumor specimens, was included in this multicenter study. At the time of analysis, 89 (73.0%) patients had experienced progression events and 44 (36.1%) had died [median follow-up 14.6 months (range, 0.53-29.5 months)]. PFS was longer for TTF-1-positive patients than for TTF-1-negative patients [median, 12.2 vs. 6.0 months; hazard ratio (HR) =0.63 (95% CI: 0.37-1.06); log-rank P=0.028]. IPTW-adjusted PFS was significantly longer for TTF-1-positive than for TTF-1-negative patients [HR =0.62 (95% CI: 0.46-0.83); log-rank P=0.024].

Conclusions: TTF-1 expression in advanced non-squamous NSCLC can serve as a basis for prediction of PFS in patients treated with PD-1/PD-L1 inhibitors plus pemetrexed and platinum chemotherapy in the first-line setting.

Keywords: Thyroid transcription factor 1 (TTF-1); chemotherapy; non-small cell lung cancer (NSCLC); programmed cell death 1 inhibitor (PD-1 inhibitor); programmed cell death ligand 1 inhibitor (PD-L1 inhibitor).

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Conflict of interest statement

Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://tlcr.amegroups.com/article/view/10.21037/tlcr-22-393/coif). EI reports personal fees from Chugai Pharmaceutical, AstraZeneca, and Lilly. KT reports personal fees from Chugai Pharmaceutical, Lilly, and MSD. IO reports grants and personal fees from Chugai Pharmaceutical, AstraZeneca, MSD, Lilly, Boehringer Ingelheim, Ono Pharmaceutical, Taiho Pharmaceutical, and Bristol-Myers Squibb; grants from Astellas Pharma, Novartis, and AbbVie; and personal fees from Pfizer outside the submitted work. The other authors have no conflicts of interest to declare.

Figures

Figure 1
Figure 1
Kaplan-Meier plots for PFS (A) and IPTW-adjusted PFS (B) according to TTF-1 expression status for the study population. PFS, progression-free survival; IPTW, inverse probability of treatment weighting; TTF-1, thyroid transcription factor 1; HR, hazard ratio; CI, confidence interval.
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