Abstract
Trastuzumab, has played a major role in improving treatment outcomes in HER-2 positive gastric cancer. However, once there is disease progression there is a paucity of evidence for second line therapy. Patient-derived xenografts (PDXs) in combination with liquid biopsies can help guide individual therapeutic decisions and have now started to be studied. In the present case we established a PDX model from a metastatic HER-2+ gastric cancer patient and after the first engraftment passage we performed a mouse clinical trial to test T-DM1 as an alternative therapy for the patient. The PDX tumor response served as a guide to administer T-DM1 therapy to the patient who responded to treatment before relapsing 6 months later. Throughout out the clinical follow up of the patient, ctDNA levels of HER-2 copy number and a PIK3CA mutation were monitored and we found their correlation with drug response and disease progression to outperform that of CEA levels. This study highlights the utility of applying precision medicine tools combining PDX models to guide therapy with circulating tumor DNA (ctDNA) to monitor treatment response and disease progression.
Highlights
Precision Medicine focuses on tailoring treatment for the tumor specific characteristics of individual patients [1]
We present a case of a patient with metastatic human epidermal growth factor receptor (HER2) positive gastric carcinoma in which treatment decisions were guided by Patient-derived xenografts (PDX) data and treatment response was monitored with circulating tumor DNA (ctDNA) markers on serial blood samples
Our case highlights how patient treatment planning can be tailored based on PDX models and how treatment response can be monitored with ctDNA
Summary
Precision Medicine focuses on tailoring treatment for the tumor specific characteristics of individual patients [1]. We present a case of a patient with metastatic human epidermal growth factor receptor (HER2) positive gastric carcinoma in which treatment decisions were guided by PDX data and treatment response was monitored with ctDNA markers on serial blood samples. This is a prime example of the power of cutting-edge personalized precision medicine based on PDX testing and ctDNA measurements in changing clinical care in oncology. We noted that ctDNA levels had already begun to fall significantly in April 2017, 3 weeks after starting T-DM1 treatment This fall in ctDNA levels of both HER-2 copy numbers and mutated PI3KCA correlated with clinical response while CEA levels were markedly increasing (Figure 3). CtDNA levels had markedly risen, coincident with disease progression, while, in contrast CEA levels had decreased and did not reflect disease status (Figure 3)
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