Phase II study of lenvatinib in patients with progressive, recurrent or metastatic adenoid cystic carcinoma Journal Article


Authors: Tchekmedyian, V.; Sherman, E. J.; Dunn, L.; Tran, C.; Baxi, S.; Katabi, N.; Antonescu, C. R.; Ostrovnaya, I.; Haque, S. S.; Pfister, D. G.; Ho, A. L.
Article Title: Phase II study of lenvatinib in patients with progressive, recurrent or metastatic adenoid cystic carcinoma
Abstract: PURPOSE Recurrent or metastatic adenoid cystic carcinoma (R/M ACC) is a malignant neoplasm of predominantly salivary gland origin for which effective therapies are lacking. We conducted a phase II trial evaluating the multitargeted tyrosine kinase inhibitor lenvatinib in patients with R/M ACC. PATIENTS AND METHODS This study was conducted with a two-stage minimax design. Patients with histologically confirmed R/M ACC of any primary site with radiographic and/or symptomatic progression were eligible. Any prior therapy was allowed except previous lenvatinib. Patients received lenvatinib 24 mg orally per day. The primary end point was overall response rate. Secondary end points were progression-free survival and safety. An exploratory analysis of how MYB expression and genomic alterations relate to outcomes was conducted. RESULTS Thirty-three patients were enrolled; 32 were evaluable for the primary end point. Five patients (15.6%) had a confirmed partial response, 24 patients (75%) had stable disease, two patients (6.3%) discontinued treatment as a result of toxicity before the first scan, and one patient (3.1%) had progression of disease as best response. Median progression-free survival time was 17.5 months (95% CI, 7.2 months to not reached), although only eight progression events were observed. Patients otherwise were removed for toxicity (n = 5), as a result of withdrawal of consent (n = 9), or at the treating physician’s discretion (n = 6). Twenty-three patients required at least one dose modification, and 18 of 32 patients discontinued lenvatinib for drug-related issues. The most common grade 3 or 4 adverse events were hypertension (n = 9; 28.1%) and oral pain (n = 3; 9.4%). Three grade 4 adverse events were observed (myocardial infarction, n = 1; posterior reversible encephalopathy syndrome, n = 1; and intracranial hemorrhage, n = 1). CONCLUSION This trial met the prespecified overall response rate primary end point, demonstrating antitumor activity with lenvatinib in R/M ACC patients. Toxicity was comparable to previous studies, requiring monitoring and management. Copyright © 2019 American Society of Clinical Oncology. All rights reserved.
Journal Title: Journal of Clinical Oncology
Volume: 37
Issue: 18
ISSN: 0732-183X
Publisher: American Society of Clinical Oncology  
Date Published: 2019-06-20
Start Page: 1529
End Page: 1537
Language: English
DOI: 10.1200/jco.18.01859
PUBMED: 30939095
PROVIDER: scopus
DOI/URL:
Notes: Article -- Export Date: 2 August 2019 -- Source: Scopus
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MSK Authors
  1. Eric J Sherman
    158 Sherman
  2. Cristina R Antonescu
    627 Antonescu
  3. Sofia S Haque
    87 Haque
  4. Nora Katabi
    167 Katabi
  5. David G Pfister
    260 Pfister
  6. Alan Loh Ho
    89 Ho
  7. Lara   Dunn
    31 Dunn
  8. Crystal Tran
    1 Tran