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1. Trophoblast Cell Surface Antigen 2 Expression in Thymic Carcinoma: Brief Report

Author

Kana Kurokawa, MD, PhD, Tetsuhiko Asao, MD, PhD, Takuo Hayashi, MD, PhD, Satsuki Kishikawa, MD, PhD, Koichiro Kanamori, MD, PhD, Takehito Shukuya, MD, PhD, Yosuke Miyashita, MD, Ikuko Nakamura, MD, PhD, Taichi Miyawaki, MD, PhD, Ryota Kanemaru, MD, PhD, Tomoyasu Mimori, MD, PhD, Yoichiro Mitsuishi, MD, PhD, Ken Tajima, MD, PhD, Naoko Shimada, MD, PhD, Fumiyuki Takahashi, MD, PhD, Kazuya Takamochi, MD, PhD, Kenji Suzuki, MD, PhD, and Kazuhisa Takahashi, MD, PhD

Subjects
TROP2, Thymic carcinoma, Immunohistochemistry, RNA-seq, Neoplasms. Tumors. Oncology. Including cancer and carcinogens, RC254-282
Abstract

Introduction: Trophoblast cell surface antigen 2 (TROP2) is a transmembrane glycoprotein overexpressed in various cancer types. Although TROP2-targeting therapy is currently attracting attention, little is known about TROP2 expression in thymic carcinoma. Methods: TROP2 gene expression in thymic epithelial tumors was analyzed using RNA-sequencing (RNA-seq) data for 122 cases obtained from The Cancer Genome Atlas. Immunohistochemistry (IHC) staining with anti-TROP2 antibody (SP295) was performed in 26 cases of thymic carcinoma tissues surgically resected at Juntendo University. Results: RNA-seq data analysis from The Cancer Genome Atlas revealed that TACSTD2 (gene encoding TROP2) expression was significantly higher in thymic carcinoma than in thymoma (adjusted p = 6.64e-05). There was also a trend of increasing expression in the order of thymoma type B1, B2, B3, and thymic carcinoma. As for IHC in thymic carcinoma, TROP2 expression was localized to the membrane of cancer cells. Intensity 0, 1, and 2 was observed in six (23.1%), 11 (42.3%), and nine (34.6%) cases, respectively, leading to TROP2 positivity in 20 cases (76.9%). The median proportion of TROP2-positive tumor cells and the median H-score were 25.0% (range: 0%–100%) and 25.0 (range: 0–200), respectively. No relevant factors were identified in the analysis of TROP2 expression and patient background. Although not significant, high TROP2 expression (H-score ≥ 50) tended to be associated with shorter survival. Conclusions: TROP2 expression in thymic carcinoma was confirmed by both RNA-seq and IHC, with high expression observed in IHC for intensity (76.9%) and proportion. TROP2 could be a potential target in thymic carcinoma.

Published
2024
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2. A Retrospective, Multicenter, Observational Study to Evaluate Clinical Outcomes of Lorlatinib After Alectinib in Patients With ALK-Positive NSCLC in Japan

Author

Yasushi Goto, MD, PhD, Hirotsugu Kenmotsu, MD, PhD, Motohiro Tamiya, MD, Shuji Murakami, MD, Takayasu Kurata, MD, Noriko Yanagitani, MD, Hirokazu Taniguchi, MD, PhD, Shoichi Kuyama, MD, PhD, Junichi Shimizu, MD, PhD, Toshihide Yokoyama, MD, Naoko Shimada, MD, PhD, Tadashi Maeda, MD, Akihiro Tamiya, MD, Ayumi Uchiyama, MD, Kazuyoshi Imaizumi, MD, Takayuki Takahama, MD, PhD, Terufumi Kato, MD, Hidetoshi Hayashi, MD, PhD, Naoko Shiraiwa, MSc, Shigeyuki Toyoizumi, MSc, Hironori Kikkawa, PhD, Despina Thomaidou, MSc, and Makoto Nishio, MD, PhD

Subjects
Non–small cell lung cancer, Anaplastic lymphoma kinase, Tyrosine kinase inhibitor, Lorlatinib, Real-world data, Neoplasms. Tumors. Oncology. Including cancer and carcinogens, RC254-282
Abstract

Introduction: Lorlatinib is an ALK tyrosine kinase inhibitor approved in Japan for the treatment of advanced ALK+ NSCLC. There has been little evidence about lorlatinib efficacy after first-line (1L) alectinib in clinical practice in Japan. Methods: We retrospectively analyzed patients with advanced ALK+ NSCLC previously treated with 1L alectinib at multiple sites in Japan. Primary objectives were to collect patient demographics at baseline and estimate time to treatment failure (TTF) with second-line (2L) or third-line (3L) or later line (≥3L) lorlatinib treatment. Secondary objectives included objective response rate (ORR) with lorlatinib, reason for discontinuation and time to last treatment failure with lorlatinib, TTF and ORR of alectinib, and combined TTF. Results: Among the 51 patients included in the study, 29 (56.9%) received 2L and 22 (43.1%) received ≥3L lorlatinib treatment. At lorlatinib initiation, brain metastases were reported in 25 patients (49.0%), and 32 (62.7%) had an Eastern Cooperative Oncology Group performance status of 0 or 1. Median TTF with lorlatinib was 11.1 months (95% confidence interval [CI]: 4.6–13.8) in any line, 10.8 months (95% CI: 3.9–13.8) in 2L, and 11.5 months (95% CI: 2.9–not reached) in ≥3L. Median TTF was 11.5 months (95% CI: 3.9–not reached) in patients with brain metastases at lorlatinib initiation and 9.9 months (95% CI: 4.3–13.8) in patients without brain metastases. ORR was 35.7% with any-line lorlatinib treatment. Conclusions: Patient characteristics and efficacy were comparable with previous reports when lorlatinib was given after 1L alectinib in patients with ALK+ NSCLC.

Published
2023
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