Jun Sato1, Miyako Satouchi2, Shoichi Itoh2, Yusuke Okuma3, Seiji Niho4, Hidenori Mizugaki5, Haruyasu Murakami6, Yasuhito Fujisaka7, Toshiyuki Kozuki8, Kenichi Nakamura9, Yukari Nagasaka9, Mamiko Kawasaki9, Tomoaki Yamada9, Ryunosuke Machida10, Aya Kuchiba10, Yuichiro Ohe11, Noboru Yamamoto12. 1. Department of Experimental Therapeutics, National Cancer Center Hospital, Tokyo, Japan. 2. Department of Thoracic Oncology, Hyogo Cancer Center, Hyogo, Japan. 3. Department of Thoracic Oncology and Respiratory Medicine, Tokyo Metropolitan Cancer and Infectious Diseases Center, Komagome Hospital, Tokyo, Japan. 4. Department of Thoracic Oncology, National Cancer Center Hospital East, Chiba, Japan. 5. First Department of Medicine, Hokkaido University Hospital, Hokkaido, Japan. 6. Division of Thoracic Oncology, Shizuoka Cancer Center, Shizuoka, Japan. 7. Department of Respiratory Medicine and Thoracic Oncology/Clinical Research Center, Osaka Medical College Hospital, Osaka, Japan. 8. Department of Thoracic Oncology and Medicine, National Hospital Organization Shikoku Cancer Center, Ehime, Japan. 9. Clinical Research Support Office, National Cancer Center Hospital, Tokyo, Japan. 10. Biostatistics Division, Center for Research Administration and Support, National Cancer Center Hospital, Tokyo, Japan. 11. Department of Thoracic Oncology, National Cancer Center Hospital, Tokyo, Japan. 12. Department of Experimental Therapeutics, National Cancer Center Hospital, Tokyo, Japan. Electronic address: nbryamam@ncc.go.jp.
Abstract
BACKGROUND: Thymic carcinoma is a rare malignant disease and standard treatment for advanced or metastatic thymic carcinoma previously treated with platinum-based chemotherapy has not been established. Lenvatinib is a novel multi-targeted inhibitor of VEGFR, FGFR, RET, c-Kit, and other kinases. The aim of this trial was to assess the activity and safety of lenvatinib as a second-line treatment in thymic carcinoma. METHODS: This single-arm, phase 2 trial done in eight institutions in Japan (five cancer centres, two medical university hospitals, and one public hospital) enrolled patients with pathologically confirmed unresectable advanced or metastatic thymic carcinoma that progressed following at least one platinum-based chemotherapy. Key inclusion criteria were age 20 years or older, at least one measurable lesion as defined by the Response Evaluation Criteria in Solid Tumors version 1.1, and an Eastern Cooperative Oncology Group performance status of 0 or 1. Patients received 24 mg of lenvatinib orally once daily in 4-week cycles until disease progression or occurrence of unacceptable adverse events. The primary endpoint was objective response rate evaluated at the data cutoff date (Feb 22, 2019), by independent central review in the intention-to-treat population. This trial is registered on JMACCT, JMA-IIA00285, and on UMIN-CTR, UMIN000026777. FINDINGS: Between April 21, 2017, and Feb 22, 2018, 42 patients were enrolled and all patients were included in the activity and safety analysis. The median follow-up period was 15·5 months (IQR 13·1-17·5). The objective response rate was 38% (90% CI 25·6-52·0, p<0·0001). 16 (38%) of 42 patients had a partial response and 24 (57%) had stable disease. The most frequent grade 3 treatment-related adverse events were hypertension (27 [64%]) and palmar-plantar erythrodysaesthesia syndrome (three [7%]). No patient died from adverse events. INTERPRETATION: The activity and safety of lenvatinib in patients with advanced or metastatic thymic carcinoma was confirmed. These results suggest that lenvatinib could become a standard treatment option for patients with previously treated advanced or metastatic thymic carcinoma. FUNDING: Center for Clinical Trials, Japan Medical Association.
BACKGROUND:Thymic carcinoma is a rare malignant disease and standard treatment for advanced or metastatic thymic carcinoma previously treated with platinum-based chemotherapy has not been established. Lenvatinib is a novel multi-targeted inhibitor of VEGFR, FGFR, RET, c-Kit, and other kinases. The aim of this trial was to assess the activity and safety of lenvatinib as a second-line treatment in thymic carcinoma. METHODS: This single-arm, phase 2 trial done in eight institutions in Japan (five cancer centres, two medical university hospitals, and one public hospital) enrolled patients with pathologically confirmed unresectable advanced or metastatic thymic carcinoma that progressed following at least one platinum-based chemotherapy. Key inclusion criteria were age 20 years or older, at least one measurable lesion as defined by the Response Evaluation Criteria in Solid Tumors version 1.1, and an Eastern Cooperative Oncology Group performance status of 0 or 1. Patients received 24 mg of lenvatinib orally once daily in 4-week cycles until disease progression or occurrence of unacceptable adverse events. The primary endpoint was objective response rate evaluated at the data cutoff date (Feb 22, 2019), by independent central review in the intention-to-treat population. This trial is registered on JMACCT, JMA-IIA00285, and on UMIN-CTR, UMIN000026777. FINDINGS: Between April 21, 2017, and Feb 22, 2018, 42 patients were enrolled and all patients were included in the activity and safety analysis. The median follow-up period was 15·5 months (IQR 13·1-17·5). The objective response rate was 38% (90% CI 25·6-52·0, p<0·0001). 16 (38%) of 42 patients had a partial response and 24 (57%) had stable disease. The most frequent grade 3 treatment-related adverse events were hypertension (27 [64%]) and palmar-plantar erythrodysaesthesia syndrome (three [7%]). No patient died from adverse events. INTERPRETATION: The activity and safety of lenvatinib in patients with advanced or metastatic thymic carcinoma was confirmed. These results suggest that lenvatinib could become a standard treatment option for patients with previously treated advanced or metastatic thymic carcinoma. FUNDING: Center for Clinical Trials, Japan Medical Association.
Authors: Fabrizio Minervini; Laura Boschetti; Michael Gregor; Mariano Provencio; Virginia Calvo; Peter B Kestenholz; Savvas Lampridis; Davide Patrini; Pietro Bertoglio; L Filipe Azenha; Consolato M Sergi; Gregor J Kocher Journal: Gland Surg Date: 2021-11
Authors: Flávia Melo Cunha de Pinho Pessoa; Caio Bezerra Machado; Emerson Lucena da Silva; Laudreísa da Costa Pantoja; Rodrigo Monteiro Ribeiro; Maria Elisabete Amaral de Moraes; Manoel Odorico de Moraes Filho; Raquel Carvalho Montenegro; André Salim Khayat; Caroline Aquino Moreira-Nunes Journal: Int J Mol Sci Date: 2022-03-30 Impact factor: 5.923