Title |
Targeted therapies for targeted populations: Anti-EGFR treatment for EGFR amplified gastroesophageal adenocarcinoma
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Published in |
Cancer Discovery, May 2018
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DOI | 10.1158/2159-8290.cd-17-1260 |
Pubmed ID | |
Authors |
Steven B Maron, Lindsay Alpert, Heewon A Kwak, Samantha Lomnicki, Leah Chase, David Xu, Emily O'Day, Rebecca J Nagy, Richard B Lanman, Fabiola Cecchi, Todd Hembrough, Alexa Schrock, John Hart, Shu-Yuan Xiao, Namrata Setia, Daniel V T Catenacci |
Abstract |
Previous anti-EGFR trials in unselected gastroesophageal adenocarcinoma (GEA) patients were resoundingly negative. We identified EGFR amplification in 5% (19/363) of patients at the University of Chicago, including 6% (8/140) who were prospectively screened with intention-to-treat using anti-EGFR therapy. Seven pts received >1 dose of treatment: three first line FOLFOX plus ABT-806, one second line FOLFIRI plus cetuximab, and three third/fourth line cetuximab alone. Treatment achieved objective response in 58% (4/7) and disease control in 100% (7/7) with a median progression-free survival of 10 months. Pre and post-treatment tumor NGS, serial plasma ctDNA NGS, and tumor IHC/FISH for EGFR revealed pre-existing and/or acquired genomic events including EGFR negative clones, PTEN deletion, KRAS amplification/mutation, NRAS, MYC and HER2 amplification, and GNAS mutations serving as mechanisms of resistance. Two evaluable patients demonstrated interval increase of CD3+ infiltrate, including one who demonstrated increased NKp46+, and PD-L1 IHC expression from baseline, suggesting an immune therapeutic mechanism of action. EGFR amplification predicted benefit from anti-EGFR therapy, albeit until various resistance mechanisms emerged. |
X Demographics
Geographical breakdown
Country | Count | As % |
---|---|---|
United States | 19 | 44% |
France | 2 | 5% |
United Kingdom | 2 | 5% |
Canada | 1 | 2% |
Brazil | 1 | 2% |
Italy | 1 | 2% |
India | 1 | 2% |
Turkey | 1 | 2% |
Colombia | 1 | 2% |
Other | 0 | 0% |
Unknown | 14 | 33% |
Demographic breakdown
Type | Count | As % |
---|---|---|
Members of the public | 21 | 49% |
Practitioners (doctors, other healthcare professionals) | 10 | 23% |
Scientists | 9 | 21% |
Science communicators (journalists, bloggers, editors) | 3 | 7% |
Mendeley readers
Geographical breakdown
Country | Count | As % |
---|---|---|
Unknown | 98 | 100% |
Demographic breakdown
Readers by professional status | Count | As % |
---|---|---|
Student > Ph. D. Student | 15 | 15% |
Researcher | 12 | 12% |
Student > Bachelor | 9 | 9% |
Student > Doctoral Student | 8 | 8% |
Other | 8 | 8% |
Other | 22 | 22% |
Unknown | 24 | 24% |
Readers by discipline | Count | As % |
---|---|---|
Medicine and Dentistry | 37 | 38% |
Biochemistry, Genetics and Molecular Biology | 17 | 17% |
Agricultural and Biological Sciences | 4 | 4% |
Pharmacology, Toxicology and Pharmaceutical Science | 3 | 3% |
Immunology and Microbiology | 3 | 3% |
Other | 10 | 10% |
Unknown | 24 | 24% |