HER2 inhibition in gastro-oesophageal cancer: A review drawing on lessons learned from breast cancer

Table 2 Selected perioperative (neoadjuvant + adjuvant) clinical trials currently underway targeting HER2 in HER2-amplified localised gastro-oesophageal cancer

Official study title	Stage and study number	Treatment arms	Estimated enrollment	Primary endpoint
Trastuzumab
A randomized phase II trial of systemic chemotherapy with and without trastuzumab followed by surgery in HER2-positive advanced gastric or esophagogastric junction adenocarcinoma with extensive lymph node metastasis: Japan Clinical Oncology Group study JCOG1301 (Trigger Study)[23]	Phase II UMIN 000016920	Preoperative S-1 + cisplatin + trastuzumab vs S-1 + cisplatin Followed by adjuvant chemotherapy with S-1 for 1 yr	130	OS
Multicenter, explorative phase II study of perioperative 5-FU, leucovorin, docetaxel, and oxaliplatin (FLOT) in combination with trastuzumab in patients with HER2-positive, locally advanced, resectable adenocarcinoma of the gastroesophageal junction or stomach (HerFLOT)	Phase II NCT01472029	Pre-operative 5-FU + leucovorin + docetaxel + oxaliplatin (FLOT) + trastuzumab Post-operative trastuzumab monotherapy	53	pCR
Trastuzumab plus XELOX for HER2-positive stage III gastric cancer after D2 gastrectomy: prospective observational Study[77]	Phase II NCT02250209	Trastuzumab + capecitabine + oxaliplatin after D2 gastrectomy	40	3-yr DFS
A phase III trial evaluating the addition of trastuzumab to trimodality treatment of HER2-overexpressing esophageal adenocarcinoma	Phase III NCT01196390	Radiotherapy + paclitaxel + carboplatin + trastuzumab vs Radiotherapy + paclitaxel + carboplatin	591	DFS
Lapatinib
A randomised phase II/III trial of peri-operative chemotherapy with or without bevacizumab in operable oesophagogastric adenocarcinoma and a feasibility study evaluating lapatinib in HER-2 positive oesophagogastric adenocarcinomas and (in selected centres) MRI and PET/CT sub-studies (STO3 trial)	Phase II/III NCT00450203	Epirubicin + cisplatin + capecitabine (ECX) + lapatinib vs ECX	40 (within lapatinib sub-study)	Safety
Pertuzumab + Trastuzumab
INtegratioN of trastuzumab, with or without pertuzumab, into perioperatiVe chemotherApy of HER-2 positive stomach cancer: the INNOVATION-TRIAL[77]	Phase II NCT02205047	Cisplatin/capecitabine or cisplatin/5-fluorouracil vs cisplatin/capecitabine + trastuzumab or cisplatin/5-fluorouracil + trastuzumab vs cisplatin/capecitabine + trastuzumab +pertuzumab or cisplatin/5-fluorouracil + trastuzumab + pertuzumab	220	Near complete pathological response rate
FLOT vs FLOT/Herceptin/Pertuzumab for perioperative therapy of adenocarcinoma of the stomach and gastroesophageal junction expressing HER-2 A phase II/III trial of the AIO. (PETRARCA study)	Phase II/III NCT02581462	5-FU + leucovorin + docetaxel + oxaliplatin (FLOT) vs FLOT + trastuzumab + Pertuzumab	404	pCR OS
Feasibility study of chemoradiation, TRAstuzumab and pertuzumab in resectable HER2+esophageal carcinoma: the TRAP study	Phase I/II NCT02120911	Pertuzumab + trastuzumab + standard chemoradiation with carboplatin and paclitaxel.	40	Safety

pCR: Pathological complete response; DFS: Disease-free survival.