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; Yasuto Yoneshima; Mikiko Hashisako; Norikazu Matsuo; Taishi Harada; Yuko Tsuchiya-Kawano; Junji Kishimoto; Keiichi Ota; Yoshimasa Shiraishi; Eiji Iwama; Kentaro Tanaka; Yoshinao Oda; Isamu Okamoto

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

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

Authors

Affiliations

¹ Department of Respiratory Medicine, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan.
² Department of Anatomic Pathology, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan.
³ Division of Respirology, Neurology, and Rheumatology, Department of Internal Medicine, Kurume University School of Medicine, Fukuoka, Japan.
⁴ Department of Respiratory Medicine, Japan Community Health Care Organization-Kyushu Hospital, Fukuoka, Japan.
⁵ Department of Respiratory Medicine, Kitakyushu Municipal Medical Center, Fukuoka, Japan.
⁶ Department of Research and Development of Next Generation Medicine, Kyushu University, Fukuoka, Japan.

^# Contributed equally.

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).