Advanced cancer of the stomach and the gastro-esophageal junction (G/GEJ) remains a very serious disease. Today, only about 10-15% of patients are alive after 5 years. Treatments mainly aim to control symptoms, extend life, and maintain quality of life.
First treatments usually combine two chemotherapies, but recent years have brought real progress. Immunotherapy - drugs that "unlock" the immune system - has shown clear benefits. For patients whose tumors have certain markers (like PD-L1), combining drugs such as nivolumab or pembrolizumab with chemotherapy can help patients live longer. Another breakthrough is zolbetuximab, a targeted therapy that attacks a protein (Claudin 18.2) found on many gastric cancers, also improving survival.
When cancer grows despite these therapies, second-line treatments are used. The most common is chemotherapy with paclitaxel + ramucirumab, which blocks the tumor's blood supply. These drugs extend survival, but usually only by a few months.
For patients who need a third option, the oral drug trifluridine/tipiracil (TAS-102) can provide extra time, though benefits remain limited. That's why researchers are now exploring combinations. Since stomach tumors rely on forming new blood vessels, combining trifluridine/tipiracil with anti-angiogenic drugs - medicines that cut off the tumor's blood supply - looks promising.
One of the most exciting of these drugs is fruquintinib, already proven effective in colorectal cancer. A new international trial, FRUQUITAS (ENGIC 06/PRODIGE 114), is now testing whether adding fruquintinib to trifluridine/tipiracil can improve survival for patients with advanced stomach or gastro-esophageal cancer.
Age ≥ 18 years (patients enrolled gender independently).
Histologically proven metastatic adenocarcinoma of the stomach or the esophagogastric junction (GEJ) or esophagus.
Prior treatment by two or three lines of treatment for metastatic setting (patients who received adjuvant therapy and developed metastatic disease within 6 months of completing treatment should be considered as having failed first-line therapy for metastatic disease).
Prior treatment (progression or intolerance) with platinum salts (oxaliplatin or cisplatin), fluoropyrimidine and irinotecan and/or taxane (+/- anti-HER2 agents +/- immune checkpoint inhibitors +/- ramucirumab +/- anti-claudin 18.2).
Concurrent enrolment in another clinical study - unless it is an observational study or during the follow-up for survival status update only of an interventional study.
Administration of the last dose of anticancer therapy and palliative radiotherapy ≤ 2 weeks prior to the first dose of study drug.
Current or prior bowel obstruction within 28 days before the first dose of study drugs.
Any unresolved clinical significant toxicity NCI CTCAE v5.0 ≥ grade 2 from previous anticancer therapy (except neuropathy).
Federation Francophone de Cancerologie Digestive
Lead sponsor
Takeda Development Center Americas, Inc.
Collaborator