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)

• Published in: Cancer 2017-06, Vol.123 (11), p.1958-1964
• Main Authors: 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
• Format: Article
• Language: English
• Subjects: Adenocarcinoma - drug therapy; Adenocarcinoma - secondary; Adenoid; Adult; Aged; Anticancer properties; Antineoplastic Agents - therapeutic use; Antitumor activity; Bone Neoplasms - drug therapy; Bone Neoplasms - secondary; Cancer; Carcinoma, Adenoid Cystic - drug therapy; Carcinoma, Adenoid Cystic - secondary; Carcinoma, Mucoepidermoid - drug therapy; Carcinoma, Mucoepidermoid - secondary; Chemotherapy; Clinical trials; Confidence intervals; Disease control; Early Termination of Clinical Trials; Enzyme inhibitors; Enzymes; Female; Fibroblast growth factor receptor 1; Fibroblast growth factor receptor 2; Fibroblast growth factor receptors; Group dynamics; Growth factors; Head & neck cancer; Head and Neck Neoplasms - drug therapy; Head and Neck Neoplasms - pathology; Humans; Indoles - therapeutic use; Liver; Liver Neoplasms - drug therapy; Liver Neoplasms - secondary; Lung Neoplasms - drug therapy; Lung Neoplasms - secondary; Male; Metastases; Metastasis; Middle Aged; Minimax technique; Nausea; Neoplasm Recurrence, Local - drug therapy; Neoplasm Recurrence, Local - pathology; nintedanib; Oncology; Oral cancer; Palliative Care; Patients; Platelet-derived growth factor; Pleural Neoplasms - drug therapy; Pleural Neoplasms - secondary; Protein-tyrosine kinase receptors; Republic of Korea; Salivary gland; salivary gland cancer; Salivary Gland Neoplasms - drug therapy; Salivary Gland Neoplasms - pathology; Stabilization; Survival; Toxic diseases; Toxicity; Treatment Failure; Tyrosine; Vascular endothelial growth factor; vascular endothelial growth factor receptor (VEGFR); Vascular endothelial growth factor receptors; Vomiting
• ISSN: 0008-543X; 1097-0142
• DOI: 10.1002/cncr.30537

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