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Ann Oncol. 2016 May;27(5):920-6. doi: 10.1093/annonc/mdw042. Epub 2016 Feb 15.

What hides behind the MASC: clinical response and acquired resistance to entrectinib after ETV6-NTRK3 identification in a mammary analogue secretory carcinoma (MASC).

Author information

1
Department of Medicine, Memorial Sloan Kettering Cancer Center, New York Department of Medicine, Weill Cornell Medical College, New York.
2
Ignyta, San Diego.
3
Department of Pathology.
4
Department of Epidemiology and Biostatistics, Memorial Sloan Kettering Cancer Center, New York.
5
Drug Development Program, Sarah Cannon Research Institute, Nashville.
6
Department of Drug Development, Florida Cancer Specialists, Sarasota.
7
Department of Medicine, Georgetown University, Washington.
8
Department of Medicine, University of California Irvine School of Medicine, Orange.
9
Department of Medicine, Massachusetts General Hospital, Boston, USA.
10
Department of Medicine, Memorial Sloan Kettering Cancer Center, New York Department of Medicine, Weill Cornell Medical College, New York hoa@mskcc.org.

Abstract

BACKGROUND:

Mammary analogue secretory carcinoma (MASC) is a recently described pathologic entity. We report the case of a patient with an initial diagnosis of salivary acinic cell carcinoma later reclassified as MASC after next-generation sequencing revealed an ETV6-NTRK3 fusion.

PATIENTS AND METHODS:

This alteration was targeted with the pan-Trk inhibitor entrectinib (Ignyta), which possesses potent in vitro activity against cell lines containing various NTRK1/2/3 fusions.

RESULTS:

A dramatic and durable response was achieved with entrectinib in this patient, followed by acquired resistance that correlated with the appearance of a novel NTRK3 G623R mutation. Structural modeling predicts that this alteration sterically interferes with drug binding, correlating to decreased sensitivity to drug inhibition observed in cell-based assays.

CONCLUSIONS:

This first report of clinical activity with TrkC inhibition and the development of acquired resistance in an NTRK3-rearranged cancer emphasize the utility of comprehensive molecular profiling and targeted therapy for rare malignancies (NCT02097810).

KEYWORDS:

ETV6-NTRK3; TrkC; entrectinib; mammary analogue secretory carcinoma

PMID:
26884591
PMCID:
PMC4843186
DOI:
10.1093/annonc/mdw042
[Indexed for MEDLINE]
Free PMC Article

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