Shifting paradigm in locally advanced resectable gastric and gastroesophageal junction cancers

Table 1 Key trials investigating the role of immunotherapy in the perioperative setting for gastric and gastroesophageal junction cancers

Ref.	Trial (design), participants (n)	Intervention arms vs comparator	Efficacy	Adverse events (grade 3 and 4)
[13]	MATTERHORN (phase III), 948	Durvalumab + FLOT (2 cycles), surgery, durvalumab + FLOT (2 cycles), durvalumab (10 cycles)	pCR: 19% vs 7%; 2-years EFS: 67% vs 59% (HR = 0.73; 95%CI: 0.60-0.89; P < 0.001); 2-year OS: 76% vs 70% (P = 0.024)	Grade 3-4 AEs during neoadjuvant phase: Similar between arms. Most common: Neutropenia, diarrhea, nausea, anemia
		Comparator: Placebo + FLOT (2 cycles), surgery, placebo + FLOT (2 cycles), placebo (10 cycles)
[17]	KEYNOTE-585 (phase III), 804	Pembrolizumab + CT: Pembrolizumab + cisplatin-based doublet (3 cycles), surgery, pembrolizumab + doublet (3 cycles), pembrolizumab (11 cycles)	pCR: 12.9% vs 2.0% (P < 0.0001); median EFS: 44.4 months vs 25.3 months (HR = 0.81; 95%CI: 0.67-0.99; P = 0.0178, NS); median OS: 60.7 months vs 58.0 months (P = 0.174, NS)	Grade 3-4 AEs: 78% (pembrolizumab + CT) vs 74% (CT). Most common: Neutropenia, anemia, diarrhea, nausea, vomiting, decreased appetite
		Comparator: Placebo + cisplatin-based doublet (3 cycles), surgery, placebo + doublet (3 cycles), placebo (11 cycles)
[12]	Retrospective, 299	Sintilimab + SOX: Sintilimab + SOX (2-4 cycles), surgery, sintilimab + SOX (2-4 cycles)	ORR: 70.4% vs 52.9% vs 59.3%; median EFS: 30 months vs 22 months vs 25 months (P = 0.054); median OS: 32 months vs 29 months vs 27 months (P = 0.007)	Grade 3-4 AEs: Overall incidence: 19.8% (sintilimab + SOX) vs 16.1% (SOX) vs 20.0% (P-SOX)
		SOX: SOX (2-4 cycles), surgery, SOX (2-4 cycles)
		P-SOX: P-SOX (2-4 cycles), surgery, P-SOX (2-4 cycles)

FLOT: 5-fluorouracil, leucovorin, oxaliplatin, docetaxel; pCR: Pathologic complete response; EFS: Event-free survival; HR: Hazard ratio; CI: Confidence interval; OS: Overall survival; NS: Not statistically significant; ORR: Objective response rate; AEs: Adverse events; CT: Chemotherapy; SOX: Oxaliplatin and S-1; P-SOX: Nab-paclitaxel, oxaliplatin, S-1.