Youjin Kim1, Su Jin Lee1, Ji Yun Lee1, Se-Hoon Lee1, Jong-Mu Sun1, Keunchil Park1, Ho Jung An2, Jae Yong Cho3, Eun Joo Kang4, Ha-Young Lee5, Jinsoo Kim6, Bhumsuk Keam7, Hye Ryun Kim8, Kyoung Eun Lee9, Moon Young Choi10, Ki Hyeong Lee11, Myung-Ju Ahn1. 1. Division of Hematology-Oncology, Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea. 2. St Vincent's Hospital, Catholic University, Suwon, South Korea. 3. Gangnam Severance Hospital, Yonsei University College of Medicine, Seoul, Korea. 4. Guro Hospital, Korea University Medical Center, Seoul, Korea. 5. Dongnam Institute of Radiological and Medical Sciences, Busan, Korea. 6. Boramae Medical Center, Seoul National University Hospital, Seoul, Korea. 7. Seoul National University Hospital, Seoul, Korea. 8. Yonsei Cancer Center, Yonsei University College of Medicine, Seoul, Korea. 9. Ewha Womans University Medical Center, Seoul, Korea. 10. Paik Hospital, Inje University, Gimhae, Korea. 11. Chungbuk National University Hospital, Cheongju, Korea.
Abstract
BACKGROUND: Salivary gland cancers (SGCs) are uncommon and account for less than 5% of all head and neck cancers, but they are histologically heterogeneous. No specific therapy, including targeted agents, has consistently improved clinical outcomes in recurrent/metastatic SGC. Recent studies suggest that vascular endothelial growth factor receptor (VEGFR) and platelet-derived growth factor receptor (PDGFR) play important roles in SGC. Nintedanib is a potent small-molecule, triple-receptor tyrosine kinase inhibitor (VEGFR1, VEGFR2, and VEGFR3; fibroblast growth factor receptor 1 [FGFR1], FGFR2, and FGFR3; and PDGFRα and PDGFRß). This study sought to determine the antitumor activity of nintedanib in patients with recurrent or metastatic SGC. METHODS: This open-label, multicenter, phase 2, single-arm study was conducted at 11 hospitals in South Korea. Patients with pathologically confirmed recurrent and/or metastatic SGC for whom at least 1 line of systemic chemotherapy had failed were enrolled. Nintedanib was given orally at 200 mg twice a day until disease progression or unacceptable toxicity. The primary endpoint was the response rate. The secondary endpoints were progression-free survival, overall survival, toxicity, and the disease-control rate. The Simon 2-stage minimax design was used. RESULTS: The median age of the patients was 54 years, 60% were female, and 95% had an Eastern Cooperative Oncology Group performance status of 0 or 1. The majority of the patients had adenoid cystic carcinoma (65%), and 40% received at least 2 prior rounds of chemotherapy. After 20 patients were enrolled, the study was stopped because no responders were observed at stage I. There were no partial responses, but the disease-control rate was 75% (15 of 20). The median duration of stable disease was 8.2 months (range, 1.76-12.36 months). At the time of the data cutoff, with a median follow-up of 9.5 months, the median overall survival had not been reached, and the progression-free survival rate at 6 months was 60% (95% confidence interval, 0.34-0.79). Grade 3 adverse events included liver enzyme elevation (25%) and nausea/vomiting (5%). Four patients who required a dose reduction because of a grade 3 liver enzyme elevation showed no further grade 3 events. CONCLUSIONS: Single-agent nintedanib did not yield a partial response but did achieve a 75% disease-control rate with long-term stabilization in SGC patients. Because of the high rate and long duration of disease control with a good safety profile, further investigation is warranted. Cancer 2017;123:1958-1964.
BACKGROUND:Salivary gland cancers (SGCs) are uncommon and account for less than 5% of all head and neck cancers, but they are histologically heterogeneous. No specific therapy, including targeted agents, has consistently improved clinical outcomes in recurrent/metastatic SGC. Recent studies suggest that vascular endothelial growth factor receptor (VEGFR) and platelet-derived growth factor receptor (PDGFR) play important roles in SGC. Nintedanib is a potent small-molecule, triple-receptor tyrosine kinase inhibitor (VEGFR1, VEGFR2, and VEGFR3; fibroblast growth factor receptor 1 [FGFR1], FGFR2, and FGFR3; and PDGFRα and PDGFRß). This study sought to determine the antitumor activity of nintedanib in patients with recurrent or metastatic SGC. METHODS: This open-label, multicenter, phase 2, single-arm study was conducted at 11 hospitals in South Korea. Patients with pathologically confirmed recurrent and/or metastatic SGC for whom at least 1 line of systemic chemotherapy had failed were enrolled. Nintedanib was given orally at 200 mg twice a day until disease progression or unacceptable toxicity. The primary endpoint was the response rate. The secondary endpoints were progression-free survival, overall survival, toxicity, and the disease-control rate. The Simon 2-stage minimax design was used. RESULTS: The median age of the patients was 54 years, 60% were female, and 95% had an Eastern Cooperative Oncology Group performance status of 0 or 1. The majority of the patients had adenoid cystic carcinoma (65%), and 40% received at least 2 prior rounds of chemotherapy. After 20 patients were enrolled, the study was stopped because no responders were observed at stage I. There were no partial responses, but the disease-control rate was 75% (15 of 20). The median duration of stable disease was 8.2 months (range, 1.76-12.36 months). At the time of the data cutoff, with a median follow-up of 9.5 months, the median overall survival had not been reached, and the progression-free survival rate at 6 months was 60% (95% confidence interval, 0.34-0.79). Grade 3 adverse events included liver enzyme elevation (25%) and nausea/vomiting (5%). Four patients who required a dose reduction because of a grade 3 liver enzyme elevation showed no further grade 3 events. CONCLUSIONS: Single-agent nintedanib did not yield a partial response but did achieve a 75% disease-control rate with long-term stabilization in SGCpatients. Because of the high rate and long duration of disease control with a good safety profile, further investigation is warranted. Cancer 2017;123:1958-1964.
Authors: Sarina K Mueller; Marlen Haderlein; Sebastian Lettmaier; Abbas Agaimy; Florian Haller; Markus Hecht; Rainer Fietkau; Heinrich Iro; Konstantinos Mantsopoulos Journal: J Clin Med Date: 2022-01-29 Impact factor: 4.241
Authors: Manik Chahal; Erin Pleasance; Jasleen Grewal; Eric Zhao; Tony Ng; Erin Chapman; Martin R Jones; Yaoqing Shen; Karen L Mungall; Melika Bonakdar; Gregory A Taylor; Yussanne Ma; Andrew J Mungall; Richard A Moore; Howard Lim; Daniel Renouf; Stephen Yip; Steven J M Jones; Marco A Marra; Janessa Laskin Journal: Cold Spring Harb Mol Case Stud Date: 2018-04-02