Cure Is Possible: Extensively Metastatic HER2-Positive Gastric Carcinoma with 5 years of Complete Remission after Therapy with the FLOT Regimen and Trastuzumab

Abstract

Gastric cancer (GC) represents one of the most fatal neoplasms in gastrointestinal oncology and affected patients can only hope for cure in limited disease. In a metastatic situation however, patients have a worse prognosis finally resulting in cancer-related death. Some improvements were made by using intensified chemotherapy such as the FLOT protocol (5-FU, leucovorin, oxaliplatin and docetaxel). However, a breakthrough in the treatment of advanced GC has been achieved by pre-therapeutical tumor analysis for potentially targetable alterations. Microsatellite instability, PD-L1 expression, Epstein Barr virus, and human epidermal growth factor receptor-2 (HER2) overexpression or amplification are the most beneficial targets, if addressed, can prolong survival in a palliative situation. Whether the combination of these targeted therapeutics with chemotherapy can bring long-term survival or even a chance of cure in a metastatic situation is not clear. Here, we report the case of a 30-year-old man with GC and extensive metastases who was cured by anti-HER2 antibody Trastuzumab combined with the FLOT regime. Initial staging showed an exophytic Siewert type III tumor and extensive hepatic metastases. Histology resulted in gastric adenocarcinoma with HER2 overexpression (2+, FISH positive). Twelve courses of chemotherapy comprising Trastuzumab and FLOT were administered. After treatment, the extensive liver metastases had disappeared with no evidence of residual tumor growth on the CT scans. Monotherapy of Trastuzumab was continued until gastrectomy with D2 lymph node dissection and probing of liver tissue, which revealed no residual tumor cells. Five years after surgery, there is continued complete remission. In conclusion, Trastuzumab in combination with FLOT may have curative potential even for metastatic stages of HER-2-positive GC.

Third- and Late Line Treatments of Metastatic Gastric Cancer: Still More to Be Done

“…Targets such as microsatellite instability, PD-L1 expression, and human epidermal growth factor receptor-2 (HER2) overexpression or amplification may be addressed with the aim of personalising treatment and prolonging survival [ 18 ]. Unfortunately, at present few effective agents are available after two standard lines for mGC [ 6 ].…”

Comprehensive biomarker analysis of long-term response to trastuzumab in patients with HER2-positive advanced gastric or gastroesophageal adenocarcinoma

“…Even though this was a tremendous success, the overall survival remained poor with a median of 13.8 months [3,4]. However, several case reports and few smaller studies have reported that a subgroup of HER2-positive mGC/mGEJC patients showed prolonged survival for several years under maintenance therapy with trastuzumab alone [5][6][7][8]. To date, a biomarker that reliably identifies this long-term responder to trastuzumab treatment remains elusive.…”