Personalized therapy based on sequential molecular analysis leads to 30 months of survival in a patient with diffuse unresectable gastric linitis plastica. Issue 6 (December 2018)

• Record Type: Journal Article
• Authors: Mahjoubi, Linda; Cecchi, Fabiola; Massard, Christophe; Calabro, Fabio; Gazzah, Anas; Bahleda, Rastislav; Jamme, Philippe; Gelli, Maximiliano; Goere, Diane; Lacroix, Ludovic; Adam, Julien; Heukamp, Lukas; Trenta, Patrizia; Hembrough, Todd; Soria, Jean-Charles; Sternberg, Cora; Ducreux, Michel
• Is Part Of: Tumori. Volume 104:Issue 6(2018)
• Page Start: NP38
• Page End: NP41
• Publication Date: 2018-12
• Subjects: Stomach -- cancer -- survival -- trastuzumab; Cancer -- Periodicals; 616.994
• DOI: 10.1177/0300891618763215
• Languages: English
• ISSNs: 0300-8916

Abstract

Introduction: Diffuse gastric cancer is associated with poor prognosis. We report a patient with metastatic gastric linitis plastica harboring human epidermal growth factor receptor 2 ( HER2 ) activating mutation and HER2 amplification. Case description: The patient received 5-fluorouracil/folinic acid and oxaliplatin combined with trastuzumab/pertuzumab, resulting in disease control for 8 months. Second-line therapy with nivolumab and trastuzumab/pertuzumab was well-tolerated, with macroscopic peritoneal response. Following ovarian progression and surgical resection of ovarian metastases, immunohistochemistry of PD-L1 was negative; proteomics demonstrated normal expression of HER2 and absence of PD-L1, while genomics showed HER2 amplification, suggesting mechanisms of escape to dual HER2 blockade by downregulation of HER2 and to nivolumab by the absence of PD-L1. Based upon this and nonexpression of biomarkers of taxane resistance, therapy was changed to paclitaxel. Two and a half years after diagnosis, the patient is undergoing treatment, with excellent performance status. Conclusions: Molecular analysis and personalized therapy can help optimize treatment in difficult-to-treat cancers.