European-Australasian consensus on the management of advanced gastric and gastro-oesophageal junction cancer: current practice and new directions

Abstract

Gastric carcinoma and gastro-oesophageal junction (GC/GEJ) carcinoma remain a significant global problem, with patients presenting with symptoms often found to have advanced or metastatic disease. Treatment options for these patients have broadened in recent years with new chemotherapy agents, agents targeting angiogenic pathways and the development of immune checkpoint inhibitors (ICIs). Most initial advances have occurred in the refractory setting, where it is important to balance treatment benefits versus toxicity and patient quality of life. In the first-line treatment of advanced/metastatic GC/GEJ, platinum- and fluoropyrimidine-based chemotherapy protocols remain the backbone of therapy (with or without HER2-targeted therapy), with the FOLFIRI regimen offering an alternative in patients deemed unsuitable for a platinum agent. Microsatellite instability-high or mismatch repair-deficient cancers have been shown to benefit most from ICIs. In unselected patients previously treated with doublet or triplet platinum- and fluoropyrimidine-based chemotherapy and second-line chemotherapy with irinotecan or taxanes have formed the backbone of therapy with or without the addition of the vascular endothelial growth factor receptor-2 inhibitor ramucirumab in addition to paclitaxel. Beyond this, efficacy has been demonstrated with oral trifluridine/tipiracil and with single-agent nivolumab, in selected refractory patients. In this review, we highlight the positive evidence from key trials that have led to our current practice algorithm, with particular focus on the refractory advanced disease setting, discussing the areas of active research and highlighting the factors, including biomarkers and the influence of ethnicity, that contribute to therapeutic decision-making.

HER2-Positive Gastroesophageal Cancers Are Associated with a Higher Risk of Brain Metastasis

“…Chemotherapy remains the backbone of standard-of-care therapies for patients with advanced GOCs [ 18 , 19 ]. Fluoropyrimadines, platinums, taxanes and topoisomerase I inhibitors have all been shown to improve overall survival in metastatic GOCs [ 20 ]. Furthermore, recent phase III data have demonstrated the additional benefits of immunotherapy with checkpoint inhibitors such as Nivolumab and Pembrolizumab, both in combination with chemotherapy and as monotherapy [ 21 , 22 , 23 , 24 ].…”

Efficacy and safety of bispecific antibodies vs. immune checkpoint blockade combination therapy in cancer: a real-world comparison

“…The first-line therapies for patients with G/GEJ adenocarcinoma typically involve platinum-based chemotherapy, anti-angiogenic drugs, and ICIs, which have shown ORRs ranging from 25 to 56.7% and mOS varying from 10.4 to 17.5 months. However, the recurrence rates following these therapies remain high [ 121 ].…”

Prognostic relevance of prognostic nutritional indices in gastric or gastro-esophageal junction cancer patients receiving immune checkpoint inhibitors: a systematic review and meta-analysis

“…As a result, the benefits of surgery are much lower compared to those for early-stage patients, and some may even lose the opportunity for curative surgery. In recent years, significant progress has been made in treating gastric and gastroesophageal junction cancers through combined chemotherapy and immunotherapy, particularly with the use of immune checkpoint inhibitors (ICIs) for advanced-stage cases ( 6 ). The combination of chemotherapy with immunotherapy and the integration of immune checkpoint inhibitors with other treatments have been continuously emerging ( 7 ).…”