Perioperative immunotherapy in gastric cancer in the spotlight

Table 3 Perioperative therapy: Landmark studies assessing perioperative therapy in gastric and gastroesophageal junction adenocarcinoma

Trial name	Disease subtype	Strategy	R0 resection rate	OS
MAGIC (2006)	G/GEJ adenocarcinoma	Perioperative ECF vs surgery	79.3% (ECF) vs 70.3%; P = 0.03	5-year OS: 36.3% (ECF) vs 23%
				HR: 0.75 (0.60-0.93); P = 0.009
FFCD 9703/ACCORD (2011)	G/GEJ adenocarcinoma	Perioperative 5-FU/cisplatin vs sugery	84% (5-FU/cisplatin) vs 74%; P = 0.04	5-year OS: 38% (5-FU/cisplatin) vs 24%
				HR OS: 0.69 (0.5-0.95); P = 0.02
CRITICS (2018)	G/GEJ adenocarcinoma	Perioperative CT vs perioperative CT + postoperative radiotherapy	80% (CT) vs 82% (CT + RDT)	Median OS: 43 months vs 37 months HR 1.01 (0.84-1.22), P = 0.9
FLOT4-AIO (2019)	G/GEJ adenocarcinoma	Perioperative FLOT vs ECF/ECX	85% (FLOT) vs 78% (ECF/ECX); P = 0.0162	Median OS: 50 months vs 35 months
				HR 0.77 (0.63-0.94), P = 0.012
ESOPEC (2024)	GEJ adenocarcinoma	Perioperative FLOT vs preoperative-CRT	94.3% (FLOT) vs 95% (CRT)	3-year OS: 57.4% (FLOT) vs 50.7% (CRT) HR: 0.7 (0.53-0.92), P = 0.01
				5-year OS: 50.6% (FLOT) vs 38.7% (CRT)
			pCR: 16.7% (FLOT) vs 10.1% (CRT)	Median OS: 66 months (FLOT) vs 37 months (CRT)
TOPGEAR	G/GEJ adenocarcinoma	Preoperative CRT + perioperative CT vs perioperative CT	No R0 difference (92%)	Median OS: 46 months (CRT) vs 49 months (CT)
			pCR: 17% (CRT) vs 8% (CT)	HR: 1.05 (0.83-1.31)
RESOLVE (2021)	G/GEJ adenocarcinoma	Perioperative SOX vs	93% (perioperative SOX) vs 88% (adjuvant SOX) vs 87% (adjuvant CAPOX) P = 0.075	No OS data
		Adjuvant SOX vs adjuvant CAPOX	pCR: 19% (perioperative SOX) vs 14% (adjuvant SOX)
RESONANCE (2024)	G/GEJ adenocarcinoma	Perioperative SOX vs adjuvante SOX	94.9% (perioperative SOX) vs 83.7% (adjuvant SOX), P < 0.0001	No OS data
			pCR: 22.3%
AIO/CAO STO 0801 (2018)	GEJ adenocarcinoma	Perioperative ECX ± Pa	No difference in R0 resection rate	No difference in OS: 49% (ECX + Pa) vs 62% (ECX)
			80% (ECX + Pa) vs 82% (ECX)	HR: 1.37 (0.84-2.25), P = 0.2
HERFLOT (2014/2023)	HER2 + G/GEJ adenocarcinoma	Perioperative FLOT ± T	Preliminary data	Preliminary data
			R0 ressection rate: 92.9%	3-year OS: 82.1%
			pCR: 21.4%
PETRARCA (2022)	HER2 + G/GEJ adenocarcinoma	Perioperative FLOT ± T ± Pe	The trial was closed prematurely	The trial was closed prematurely
			R0 ressection rate: 90% (FLOT) vs 93% (FLOT + T + Pe)	Median OS not reached
			pCR: 12% (FLOT) vs 35% (FLOT + T + Pe)	HR: 0.56, P = 0.24

R0: Complete resection with no tumor within 1mm; OS: Overall survival; G/GEJ: Gastric and gastroesophageal junction; ECF: Epirubicin, cisplatin, and fluorouracil; HR: Hazard ratio; CT: Chemotherapy; RT: Radiotherapy; FLOT: Fluorouracil, leucovorin, oxaliplatin, docetaxel; 5-FU: 5-fuorouracil; RDT: Radiotherapy ; ECX: Epirubicin, cisplatin, capecitabine; CRT: Chemoradiotherapy; pCR: Complete pathological response; Pa: Panitumumab; Pe: Pertuzumab; T: Trastuzumab; SOX: S-1 and oxaliplatin; CAPOX: Capecitabine, oxaliplatin, docetaxel.