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. 2017;2017(1):PO.17.00117.
doi: 10.1200/PO.17.00117. Epub 2017 Aug 29.

Dramatic Response to Crizotinib in a Patient with Lung Cancer Positive for an HLA-DRB1-MET Gene Fusion

Kurtis D Davies  1 , Terry L Ng  2 , Adriana Estrada-Bernal  2 , Anh T Le  2 , Peter R Ennever  3 , D Ross Camidge  2 , Robert C Doebele  2 , Dara L Aisner  1
Affiliations

Dramatic Response to Crizotinib in a Patient with Lung Cancer Positive for an HLA-DRB1-MET Gene Fusion

Kurtis D Davies et al. JCO Precis Oncol. 2017.
No abstract available

PubMed Disclaimer

Conflict of interest statement

Kurtis D. Davies

No relationship to disclose

Terry L. Ng

Honoraria: ARIAD Pharmaceuticals, Takeda

Consulting or Advisory Role: Boehringer Ingelheim

Adriana Estrada-Bernal

No relationship to disclose

Anh T. Le

Patents, Royalties, Other Intellectual Property: Royalties from Abbott Molecular for a patent

Peter R. Ennever

No relationship to disclose

D. Ross Camidge

Honoraria: Roche, G1 Therapeutics, Mersana, Takeda

Research Funding: Takeda

Robert C. Doebele

Honoraria: Pfizer, AstraZeneca, ARIAD Pharmaceuticals, Guardant Health

Consulting or Advisory Role: Pfizer, OncoMed, Trovagene, Ignyta, Green Peptide, AstraZeneca

Research Funding: Mirati Therapeutics (Inst), Abbott Molecular, Loxo Oncology (Inst), Ignyta (Inst)

Patents, Royalties, Other Intellectual Property: Licensing fees from Abbott Molecular for Patent PCT/US2013/057495, licensing fees for biologic material from ARIAD Pharmaceuticals (Inst), licensing fees for biologic materials from GVKbio, licensing fees for biologic materials from Loxo Oncology (Inst)

Travel, Accommodations, Expenses: Ignyta, ARIAD Pharmaceuticals

Dara L. Aisner

Honoraria: AstraZeneca, Clovis Oncology

Consulting or Advisory Role: Inivata

Research Funding: Genentech (Inst)

Patents, Royalties, Other Intellectual Property: Patent pending for pneumatic cell collection device

Travel, Accommodations, Expenses: SeraCare

Figures

Fig 1.
Fig 1.
(A) Schematic of the detected fusion with breakpoints between exons indicated (transcript fusion breakpoints map to the following genomic coordinates [hg19]: HLA-DRB1, chromosome 6: 32548024; MET, chromosome 7: 116414935; top). Black arrow indicates the binding site for the GSP2 primer used in the anchored multiplex polymerase chain reaction (AMP) assay. Example reads from the AMP assay that supports the fusion (middle). Sequence trace from reverse transcriptase polymerase chain reaction (RT-PCR) assay that supports the fusion (bottom). (B) Image of immunohistochemical staining using an antibody to HLA class II (DR). Green circle indicates an area of tumor cells; blue circle indicates an area of macrophages. Magnification ×40.
Fig 2.
Fig 2.
(A) MET-GAB1 proximity ligation assay (PLA) analysis of formalin-fixed, paraffin-embedded samples from the HLA-DRB1-MET patient, two different MET exon 14 (ex14) skipping–positive patients, and an ALK rearrangement–positive patient (negative control). Scale bar is 50 microns. (B) Quantification of PLA analysis displayed as the average number of dots per nucleus. Data are expressed as means ± SEM. The HLA-DRB1-MET sample displayed a significantly higher PLA score than did the ALK sample, as determined by analysis of variance followed by Bonferroni’s post hoc analysis. (*) P < .001.
Fig 3.
Fig 3.
Contrast-enhanced computed tomography scans of the chest of the patient (A) before and (B) approximately 6 weeks and (C) 3 months after starting crizotinib 250 mg twice daily. Arrows highlight lung lesions before and after therapy. Shown are four of 14 lesions; the remaining 10 lesions had regressed by 6 weeks, with an ongoing response at 3 months.
See this image and copyright information in PMC

References

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