Trimodality treatment in gastric and gastroesophageal junction cancers: Current approach and future perspectives

Table 3 Chemoradiation and targeted therapies clinical trials

Study name/phase	Size/stage/primary tumor location/histology	Intervention	Primary endpoint
Ku et al[72]/phase II	33 patients/uT2-3N0-1/esophagus 33% GEJ 66%/adenocarcinoma	E: cisplatin, irinotecan + bevacizumab + 50.4 Gy radiation → surgery	Tolerability: 59% grade 3/4 hematologic toxicity 42% grade 3/4 non-hematologic toxicity (including deep vein thrombosis)
TOXAG/phase II[70]	34 patients/76% > IIIA/stomach GEJ/adenocarcinoma HER2 positive	E: gastrectomy D2 → oxaliplatin, capecitabine + 45 Gy radiation + trastuzumab	Tolerability: 90.3% completed 3 cycles of treatment
SAKK 75/08/phase III[71]	300 patients/T2N1-3, T3Nany, T4aNany/esophagus 50% GEJ 50%/adenocarcinoma 64% SCC 36%	E: docetaxel, cisplatin + 45 Gy radiation + cetuximab → surgery → cetuximab OR C: docetaxel, cisplatin + 45 Gy radiation AND surgery (both arms)	mPFS: 2.9 y experimental vs 2 y control HR 0.79; (95%CI: 0.58 to 1.07, P = 0.13)
RTOG 1010/phase III[69]	203 patients/T1N1-2, T2-3N0-2/esophagus GEJ/adenocarcinoma HER2 positive	E: carboplatin, paclitaxel + 50.4 Gy radiation + trastuzumab → surgery → trastuzumab ORC: carboplatin, paclitaxel + 50.4Gy radiation → Surgery	mDFS: 19.6 m experimental vs 14.2 control HR 0.97 (95%CI: 0.69-1.36)
CheckMate 577/phase III[66]	794 patients/II-III, ≥ ypT1 or ≥ ypN1/esophagus 60% GEJ 40%/adenocarcinoma 71% SCC 29%	Neoadjuvant chemoradiation → surgery (both arms) AND E: nivolumab OR C: placebo	mDFS: 22.4 m experimental vs 11 m control HR 0.69 (95%CI: 0.56-0.86, P = 0.0003)

mOS: Median overall survival; mDFS: Median disease-free survival; mPFS: Median progression-free survival; E: Experimental; C: Control; HR: Hazard ratio; 5-FU: 5-fluorouracil; LV: Leucovorin; Gy: Gray; S-1: Tegafur/gimeracil/oteracil; pCR: Pathologic complete response; GEJ: Gastroesophageal junction; CRT: Chemoradiation; AEG: Adenocarcinomas of the esophagogastric junction.