Phase II trial with axitinib in recurrent and/or metastatic salivary gland cancers of the upper aerodigestive tract.
Adult
Aged
Antineoplastic Agents
/ adverse effects
Axitinib
/ adverse effects
Carcinoma, Adenoid Cystic
/ drug therapy
Disease-Free Survival
Dose-Response Relationship, Drug
Drug Administration Schedule
Female
Humans
Male
Maximum Tolerated Dose
Middle Aged
Neoplasm Recurrence, Local
/ drug therapy
Risk Assessment
Salivary Gland Neoplasms
/ drug therapy
Survival Analysis
Treatment Failure
adenoid cystic carcinoma
antiangiogenetic
axitinib
salivary gland cancer
tyrosine kinase inhibitor
Journal
Head & neck
ISSN: 1097-0347
Titre abrégé: Head Neck
Pays: United States
ID NLM: 8902541
Informations de publication
Date de publication:
10 2019
10 2019
Historique:
received:
04
04
2019
revised:
10
06
2019
accepted:
11
07
2019
pubmed:
30
7
2019
medline:
12
9
2020
entrez:
30
7
2019
Statut:
ppublish
Résumé
Patients with prognosis recurrent/metastatic (R/M) salivary gland carcinomas (SGCs) are poor. Activity of axitinib was demonstrated in adenoid cystic carcinoma (ACC). We tested axitinib in a larger cohort of R/M SGCs including non-ACC. Axitinib was administered at 10 mg daily (dose escalation allowed) until progression or unacceptable toxicity. Null hypothesis would be rejected if more than 3 of 26 responses were observed. Twenty-six patients (50% were male; 6 ACC, 20 non-ACC) were treated. Response rate was 8% (2 partial responses), 13 stable disease (>6 months in 7 patients) and 11 disease progression. Median progression-free survival and overall survival were 5.5 and 26.2 months, respectively. All patients had at least one adverse event: stomatitis (69%), fatigue (58%) and hypertension (54%) were the most frequent. This trial did not meet its primary endpoint hence axitinib should not be considered for further investigations in SGCs. Safety profile was in line with the scientific literature.
Sections du résumé
BACKGROUND
Patients with prognosis recurrent/metastatic (R/M) salivary gland carcinomas (SGCs) are poor. Activity of axitinib was demonstrated in adenoid cystic carcinoma (ACC). We tested axitinib in a larger cohort of R/M SGCs including non-ACC.
METHODS
Axitinib was administered at 10 mg daily (dose escalation allowed) until progression or unacceptable toxicity. Null hypothesis would be rejected if more than 3 of 26 responses were observed.
RESULTS
Twenty-six patients (50% were male; 6 ACC, 20 non-ACC) were treated. Response rate was 8% (2 partial responses), 13 stable disease (>6 months in 7 patients) and 11 disease progression. Median progression-free survival and overall survival were 5.5 and 26.2 months, respectively. All patients had at least one adverse event: stomatitis (69%), fatigue (58%) and hypertension (54%) were the most frequent.
CONCLUSIONS
This trial did not meet its primary endpoint hence axitinib should not be considered for further investigations in SGCs. Safety profile was in line with the scientific literature.
Substances chimiques
Antineoplastic Agents
0
Axitinib
C9LVQ0YUXG
Types de publication
Clinical Trial, Phase II
Comparative Study
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
3670-3676Informations de copyright
© 2019 Wiley Periodicals, Inc.
Références
Carlson ER. Malignant salivary gland tumors. J Oral Maxillofac Surg. 2016;74(12):2340-2341.
WHO. WHO Classification of Head and Neck Tumours-4th Edition. 2017. Geneva, Switzerland: WHO.
Ciccolallo L, Licitra L, Cantu G, Gatta G. Survival from salivary glands adenoid cystic carcinoma in European populations. Oral Oncol. 2009;45(8):669-674.
Alfieri S, Granata R, Bergamini C, et al. Systemic therapy in metastatic salivary gland carcinomas: a pathology-driven paradigm? Oral Oncol. 2017;66:58-63.
Ross JS, Gay LM, Wang K, et al. Comprehensive genomic profiles of metastatic and relapsed salivary gland carcinomas are associated with tumor type and reveal new routes to targeted therapies. Ann Oncol. 2017;28(10):2539-2546.
Drilon A, Li G, Dogan S, et al. What hides behind the MASC: clinical response and acquired resistance to entrectinib after ETV6-NTRK3 identification in a mammary analogue secretory carcinoma (MASC). Annals of Oncology: Official Journal of the European Society for med Oncol. 2016;27(5):920-926.
Blochowiak KJ, Sokalski J, Bodnar MB, Trzybulska D, Marszalek AK, Witmanowski H. Expression of VEGF165b, VEGFR1, VEGFR2 and CD34 in benign and malignant tumors of parotid glands. Adv Clin Exp Med. 2018;27(1):83-90.
Fonseca FP, Basso MP, Mariano FV, et al. Vascular endothelial growth factor immunoexpression is increased in malignant salivary gland tumors. Ann Diagn Pathol. 2015;19(3):169-174.
Blochowiak K, Sokalski J, Golusinska E, et al. Salivary levels and immunohistochemical expression of selected angiogenic factors in benign and malignant parotid gland tumours. Clin Oral Investig. 2018;23(3):995-1006.
Lim JJ, Kang S, Lee MR, et al. Expression of vascular endothelial growth factor in salivary gland carcinomas and its relation to p53, Ki-67 and prognosis. J Oral Pathol Med. 2003;32(9):552-561.
Lequerica-Fernandez P, Astudillo A, de Vicente JC. Expression of vascular endothelial growth factor in salivary gland carcinomas correlates with lymph node metastasis. Anticancer Res. 2007;27(5B):3661-3666.
Locati LD, Perrone F, Cortelazzi B, et al. A phase II study of sorafenib in recurrent and/or metastatic salivary gland carcinomas: translational analyses and clinical impact. Eur J Cancer. 2016;69:158-165.
Thomson DJ, Silva P, Denton K, et al. Phase II trial of sorafenib in advanced salivary adenoid cystic carcinoma of the head and neck. Head Neck. 2015;37(2):182-187.
Rini BI, Escudier B, Tomczak P, et al. Comparative effectiveness of axitinib versus sorafenib in advanced renal cell carcinoma (AXIS): a randomised phase 3 trial. Lancet. 2011;378(9807):1931-1939.
Ho AL, Dunn L, Sherman EJ, et al. A phase II study of axitinib (AG-013736) in patients with incurable adenoid cystic carcinoma. Ann Oncol. 2016;27(10):1902-1908.
Eisenhauer EA, Therasse P, Bogaerts J, et al. New response evaluation criteria in solid tumours: revised RECIST guideline (version 1.1). Eur J Cancer. 2009;45(2):228-247.
Simon R. Optimal two-stage designs for phase II clinical trials. Control Clin Trials. 1989;10(1):1-10.
Laurie SA, Ho AL, Fury MG, Sherman E, Pfister DG. Systemic therapy in the management of metastatic or locally recurrent adenoid cystic carcinoma of the salivary glands: a systematic review. Lancet Oncol. 2011;12(8):815-824.
Laurie SA, Licitra L. Systemic therapy in the palliative management of advanced salivary gland cancers. J Clin Oncol. 2006;24(17):2673-2678.
Siekmann AF, Lawson ND. Notch signalling and the regulation of angiogenesis. Cell Adh Migr. 2007;1(2):104-106.
Jiang BH, Liu LZ. PI3K/PTEN signaling in angiogenesis and tumorigenesis. Adv Cancer Res. 2009;102:19-65.
Krejsgaard T, Vetter-Kauczok CS, Woetmann A, et al. Jak3- and JNK-dependent vascular endothelial growth factor expression in cutaneous T-cell lymphoma. Leukemia. 2006;20(10):1759-1766.
Zehir A, Benayed R, Shah RH, et al. Mutational landscape of metastatic cancer revealed from prospective clinical sequencing of 10,000 patients. Nat Med. 2017;23(6):703-713.
Weng AP, Ferrando AA, Lee W, et al. Activating mutations of NOTCH1 in human T cell acute lymphoblastic leukemia. Science. 2004;306(5694):269-271.
Ferrarotto R, Mitani Y, Diao L, et al. Activating NOTCH1 mutations define a distinct subgroup of patients with adenoid cystic carcinoma who have poor prognosis, propensity to bone and liver metastasis, and potential responsiveness to Notch1 inhibitors. J Clin Oncol. 2017;35(3):352-360.
Hutson TE, Lesovoy V, Al-Shukri S, et al. Axitinib versus sorafenib as first-line therapy in patients with metastatic renal-cell carcinoma: a randomised open-label phase 3 trial. Lancet Oncol. 2013;14(13):1287-1294.
Ho AL, Sherman EJ, Baxi SS, et al. Phase II study of regorafenib in progressive, recurrent/metastatic adenoid cystic carcinoma. J Clin Oncol. 2016;34(15_suppl):6096-6096.
Locati L, Galbiati D, Calareso G, et al. Phase II study on lenvatinib (LEN) in recurrent and/or metastatic (R/M) adenoid cystic carcinomas (ACC) of the salivary glands (SG) of the upper aereodigestive tract (NCT02860936). J Clin Oncol. 2018;36(15_suppl):6086-6086.
Tchekmedyian V, Sherman EJ, Dunn L, et al. Phase II study of Lenvatinib in patients with progressive, recurrent or metastatic adenoid cystic carcinoma. J Clin Oncol. 2019;37(18):1529-1537.