Format

Send to

Choose Destination
Cancer. 2017 Jun 1;123(11):1958-1964. doi: 10.1002/cncr.30537. Epub 2017 Jan 19.

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).

Author information

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. © 2017 American Cancer Society.

KEYWORDS:

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

PMID:
28102887
DOI:
10.1002/cncr.30537
[Indexed for MEDLINE]
Free full text

Supplemental Content

Full text links

Icon for Wiley
Loading ...
Support Center