Personalized therapy based on sequential molecular analysis leads to 30 months of survival in a patient with diffuse unresectable gastric linitis plastica.

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.

• Authors: Linda Mahjoubi, Fabiola Cecchi, Christophe Massard, Fabio Calabro, Anas Gazzah, Rastislav Bahleda, Philippe Jamme, Maximiliano Gelli, Diane Goere, Ludovic Lacroix, Julien Adam, Lukas Heukamp, Patrizia Trenta, Todd Hembrough, Jean-Charles Soria, Cora Sternberg, Michel Ducreux
• Journal: Tumori (Tumori) Vol. 104 Issue 6 Pg. NP38-NP41 (Dec 2018) ISSN: 2038-2529 [Electronic] United States
• PMID: 29714649 (Publication Type: Case Reports, Journal Article)

Chemical References

• Receptor, ErbB-2

Topics

• Antineoplastic Combined Chemotherapy Protocols (therapeutic use)
• Female
• Humans
• Linitis Plastica (drug therapy, metabolism)
• Middle Aged
• Precision Medicine (methods)
• Receptor, ErbB-2 (metabolism)
• Stomach (drug effects)
• Stomach Neoplasms (drug therapy, metabolism)