- HER2+ oesophagogastric cancer is not breast cancer.
Why this matters
- Trastuzumab is effective only as first line treatment, second line continuation is not beneficial.
- TAS102 (trifluridine + tipiracil) has shown effectiveness in refractory disease.
- First line there are two preferred regimens: S-1 + cisplatin remains the standard treatment for advanced gastric cancer (Japanese Phase III JCOG1013) and postoperative adjuvant S-1 + docetaxel is recommended as the new standard of care for advanced gastric cancer patients.
- HER2 targeted agent trastuzumab has modest first line activity in oesophagogastric cancers (TOGA cape-Cis + trastuzumab improved RR, RFS, OS).
- First line lapatinib + cape + oxaliplatin (LOGIC OS 12.2 v 10.5 mos) and pertuzumab + trastuzumab + chemotherapy (JACOB OS 17.5 vs 14.2 months) both failed to improve OS.
- Second line trastuzumab emtansine (TDM-1) was no better than a taxane in 345 patients (OS 7.9 vs 8.6 months). Possible reasons are denovo or acquired resistance due to HER2 loss.
- Novel cytotoxics: TAS102 (trifluridine + tipiracil) vs best supportive care in third or later line treatment met its primary endpoint of improved overall survival. It will become a salvage late line option.
- Coming up soon: genomics identified targetable subpopulations: RTK amplification, MSI high; FGFR inhibitors (bemartuzumab), matrix metalloproteinase inhibitors, IMAB362 targeting Claudin 18.2 are currently in phase III studies.
"Despite guidelines and recommendations for HER2 testing and treatment among patients with gastric, oesophageal, or GEJ adenocarcinomas only about ¾ of patients are tested before first line treatment and less than half of patients with HER2+ tumors received trastuzumab in the first line setting as recommended. HER2 targeted therapy is continued across lines of therapy despite lack of evidence for this practice. We need to improve testing rates and provide appropriate care to HER+ patients." Lisa M. Hess, PhD