Aggressive HER2-Positive Gastric Cancer in a Young Patient, Refractory in Trastuzumab and Progressive with Trastuzumab-Emtansine Treatment

Abstract

Gastric cancer remains a major global health problem. Gastric cancer is the fifth most frequently diagnosed cancer and the third leading cause of cancer-related deaths in the world. The prognosis of the disease is poor because it is often diagnosed at later stages, especially at HER2-positive. Most patients diagnosed with gastric cancer present with advanced, incurable disease. This report details the case of a 30-year-old male patient diagnosed with metastatic gastric adenocarcinoma. Stage T3 N3 M1, PD-L1 0%, and HER2+. The patient was administered neoadjuvant palliative chemotherapy, eight cycles of FLOT, and the last two cycles of HER-FLOT. The patient constantly had elevated levels of liver enzymes, and therefore, endoscopic retrograde cholangiopancreatography with biliary stenting was performed. After chemotherapy followed by restaging, the tumor board, based on the findings, decided to remove the primary tumor from this young patient. The operation was performed as a palliative da Vinci-assisted total gastrectomy with lymphadenectomy. Then, trastuzumab monotherapy was prescribed. At that time, the patient's follow-up with PET-CT showed progression with hypermetabolic lymph nodes in the paraaortic and aortocaval regions, as well as left hydronephrosis. As a result, we started the second-line therapy with T-DM1, an antibody-drug conjugate trastuzumab-emtansine (KADCYLA), for five cycles. At the time of receiving the sixth cycle, the patient's condition changed dramatically due to liver and heart problems, pleural effusion, and bleeding. After two years of treatment, all oncological-specific therapies have been ended, and the patient has been put in palliative care to relieve suffering and to support the best possible quality of life. This case underlines the importance of identifying potential therapeutic targets and developing therapies to improve the outcomes of systemic treatment beyond those currently achieved with conventional chemotherapy and targets.

Keywords

• gastric cancer
• her2 resistance
• trastuzumab