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Poster display

2173 - Dovitinib in advanced adenoid cystic carcinoma of the salivary glands: Ontario Clinical Oncology Group DOVE trial

Date

09 Oct 2016

Session

Poster display

Presenters

Sebastien Hotte

Citation

Annals of Oncology (2016) 27 (6): 328-350. 10.1093/annonc/mdw376

Authors

S.J. Hotte1, D. Hao2, G.R. Pond3, S.A. Laurie4, E. Winquist5, M. Filion6, M.N. Levine3

Author affiliations

  • 1 Medical Oncology, Escarpment Cancer Research Institute (ECRI) and McMaster University, L8V 5C2 - Hamilton/CA
  • 2 Oncology, Tom Baker Cancer Centre, Calgary/CA
  • 3 Oncology, Ontario Clinical Oncology Group (OCOG), McMaster University and Escarpment Cancer Research Institute (ECRI), Hamilton/CA
  • 4 Oncology, The Ottawa Hospital Regional Cancer Centre, Ottawa/CA
  • 5 Oncology, London Regional Cancer Center, London Health Science Center, University of Western Ontario, London/CA
  • 6 Oncology, Ontario Clinical Oncology Group (OCOG) and McMaster University, Hamilton/CA
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Resources

Abstract 2173

Background

Metastatic adenoid cystic carcinoma (ACC) is a rare, incurable malignancy of the salivary glands with no reliable treatment. Over 90% of ACC carry a t(6;9) translocation that leads to MYB overexpression and upregulation of the fibroblast growth factor 2 (FGF2) ligand. Dovitinib (DOV) is a receptor TKI with multiple targets including FGFR and VEGFR. In preclinical studies, DOV showed a suppressive effect in ACC xenografts. We hypothesized that DOV would have beneficial clinical effects.

Methods

Patients (pts) with incurable ACC were recruited if they had progressed within 12 months prior to study entry (> 10% change, new lesion(s), or worsening clinical status). The primary outcome was clinical benefit rate (CBR), a composite endpoint of CR, PR, or SD of > six months. Sample size of 20 evaluable pts was based on a CBR of 75%, estimated from natural history and previous studies. Archival tissue was obtained for MYB-NFIB gene translocation by FISH analysis and FGFR and phospho-FGFR expression. Pts received DOV 500mg orally 5 days on/2 days off on a 28-day cycle with response assessed every 12 weeks.

Results

21 pts (11 female) with a mean age of 55.9 years (range 38.1, 81.5) were enrolled. Best response was SD in 15 pts. CBR was 7/21 (33.3%). Five of 18 pts with measurable disease (27.8%) had some regression. PFS at 12 months was 37.6%, and 1-year OS was 61.6%. Most patients tolerated DOV reasonably well but six pts discontinued because of toxicity and five required dose reductions. The most frequent attributable AEs were diarrhea (91%), nausea (67%), fatigue (71%), rash (38%), anorexia, and vomiting (33% each). Six of 15 pts (40%) had wild type MYB by FISH. Wild type (WT) status was not prognostic for OS (p = 0.38) or PFS (p = 0.18). MYB IHC was not prognostic for either OS (p = 0.086) or PFS (p = 0.74), but pFGFR IHC score was significantly prognostic for OS (HR = 1.35, 95% CI = 1.01-1.80, p = 0.040), but not PFS (p = 0.11).

Conclusions

DOV toxicity was generally manageable with predominantly gastrointestinal adverse events. However, objective responses were not observed and the primary endpoint of clinical benefit was not met. Although tumor pFGFR IHC score appeared prognostic, no pharmacodynamic predictors of clinical activity from DOV were identified.

Clinical trial identification

NCT01678105

Legal entity responsible for the study

N/A

Funding

Novartis

Disclosure

All authors have declared no conflicts of interest.

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