Chemorefractory Gastric Cancer: The Evolving Terrain of Third-Line Therapy and Beyond

Simple Summary Gastric and gastro-oesophageal junction cancers (GC) are the fourth cause of cancer-related deaths, representing an international problem which needs a proper assessment. Beyond being an aggressive disease, which rapidly progress to different lines of treatment, patients suffering GC normally present a non-depreciable number of symptoms that make them especially fragile. In this context, sequential treatment lines with few toxic adverse events have been associated to an increased survival. A satisfactory GC therapy comprise at least three lines of treatment including chemotherapy and immunotherapy and/or targeted agents when indicated. Gastric and gastro-oesophageal junction cancer (GC) represent a global healthcare problem being the fifth most common tumour type and the fourth cause of cancer mortality. Extremely poor median survival of approximately 10 months is normally reported within advanced GC patients, mainly secondary to two factors, i.e., the fragility of these patients and the aggressiveness of this disease. In this context, the correct treatment of GC patients requires not only a multidisciplinary team with special attention to palliative and nutritional care but also a close follow-up with regular monitoring of disease symptoms and tumour evaluation. Sequential treatment lines with few toxic adverse events have emerged as the best therapeutic approach, and a third line of therapy could further improve survival and quality of life of GC patients. Chemotherapy, immunotherapy, and targeted agents -when indicated- constitute the treatment armamentarium of these patients. In this review, we discuss treatment options in the refractory setting as well as novel approaches to overcome the poor prognosis of GC.