Clinical trial of nintedanib in patients with recurrent or metastatic salivary gland cancer of the head and neck: A multicenter phase 2 study (Korean Cancer Study Group HN14-01)

Youjin Kim, Su Jin Lee, Ji Yun Lee, Se Hoon Lee, Jong Mu Sun, Keunchil Park, Ho Jung An, Jae Yong Cho, Eun Joo Kang, Ha Young Lee, Jinsoo Kim, Bhumsuk Keam, Hye Ryun Kim, Kyoung Eun Lee, Moon Young Choi, Ki Hyeong Lee, Myung Ju Ahn

Research output: Contribution to journalArticle

9 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)1958-1964
Number of pages7
JournalCancer
Volume123
Issue number11
DOIs
Publication statusPublished - 2017 Jun 1

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Salivary Gland Neoplasms
Head and Neck Neoplasms
Clinical Trials
Platelet-Derived Growth Factor Receptors
Neoplasms
Disease-Free Survival
Receptor, Fibroblast Growth Factor, Type 1
Drug Therapy
Adenoid Cystic Carcinoma
Republic of Korea
Vascular Endothelial Growth Factor Receptor
Survival
Liver
Receptor Protein-Tyrosine Kinases
Enzymes
nintedanib
Nausea
Vomiting
Disease Progression
Survival Rate

Keywords

  • nintedanib
  • salivary gland cancer
  • vascular endothelial growth factor receptor (VEGFR)

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

Cite this

Clinical trial of nintedanib in patients with recurrent or metastatic salivary gland cancer of the head and neck : A multicenter phase 2 study (Korean Cancer Study Group HN14-01). / Kim, Youjin; Lee, Su Jin; Lee, Ji Yun; Lee, Se Hoon; Sun, Jong Mu; Park, Keunchil; An, Ho Jung; Cho, Jae Yong; Kang, Eun Joo; Lee, Ha Young; Kim, Jinsoo; Keam, Bhumsuk; Kim, Hye Ryun; Lee, Kyoung Eun; Choi, Moon Young; Lee, Ki Hyeong; Ahn, Myung Ju.

In: Cancer, Vol. 123, No. 11, 01.06.2017, p. 1958-1964.

Research output: Contribution to journalArticle

Kim, Y, Lee, SJ, Lee, JY, Lee, SH, Sun, JM, Park, K, An, HJ, Cho, JY, Kang, EJ, Lee, HY, Kim, J, Keam, B, Kim, HR, Lee, KE, Choi, MY, Lee, KH & Ahn, MJ 2017, 'Clinical trial of nintedanib in patients with recurrent or metastatic salivary gland cancer of the head and neck: A multicenter phase 2 study (Korean Cancer Study Group HN14-01)', Cancer, vol. 123, no. 11, pp. 1958-1964. https://doi.org/10.1002/cncr.30537
Kim, Youjin ; Lee, Su Jin ; Lee, Ji Yun ; Lee, Se Hoon ; Sun, Jong Mu ; Park, Keunchil ; An, Ho Jung ; Cho, Jae Yong ; Kang, Eun Joo ; Lee, Ha Young ; Kim, Jinsoo ; Keam, Bhumsuk ; Kim, Hye Ryun ; Lee, Kyoung Eun ; Choi, Moon Young ; Lee, Ki Hyeong ; Ahn, Myung Ju. / Clinical trial of nintedanib in patients with recurrent or metastatic salivary gland cancer of the head and neck : A multicenter phase 2 study (Korean Cancer Study Group HN14-01). In: Cancer. 2017 ; Vol. 123, No. 11. pp. 1958-1964.
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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 PDGFR{\ss}). 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.",
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TY - JOUR

T1 - Clinical trial of nintedanib in patients with recurrent or metastatic salivary gland cancer of the head and neck

T2 - A multicenter phase 2 study (Korean Cancer Study Group HN14-01)

AU - Kim, Youjin

AU - Lee, Su Jin

AU - Lee, Ji Yun

AU - Lee, Se Hoon

AU - Sun, Jong Mu

AU - Park, Keunchil

AU - An, Ho Jung

AU - Cho, Jae Yong

AU - Kang, Eun Joo

AU - Lee, Ha Young

AU - Kim, Jinsoo

AU - Keam, Bhumsuk

AU - Kim, Hye Ryun

AU - Lee, Kyoung Eun

AU - Choi, Moon Young

AU - Lee, Ki Hyeong

AU - Ahn, Myung Ju

PY - 2017/6/1

Y1 - 2017/6/1

N2 - 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.

AB - 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.

KW - nintedanib

KW - salivary gland cancer

KW - vascular endothelial growth factor receptor (VEGFR)

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