. 2021 Dec 29;7(1):100360. doi: 10.1016/j.esmoop.2021.100360

Table 1.

Baseline characteristics

Study	Study design (study number)	Tx type	Region	Race	N	Male/female	Median age (range or IQR)	Tumor location	Stage of the disease	HER2+ expression status
Shitara Int J Clin Oncol 2020 (JACOB subgroup analysis)³⁰	Phase III^a (NCT01774786)	Placebo + Trast IV on D1 (loading dose, 8 mg/kg; maintenance dose, 6 mg/kg) Q3W + Cis 80 mg/m² IV Q3W + Cape 1000 mg/m² PO BID for 28 doses (D1-15) Q3W	Japan: 100%	Asian: 100%	40	70%/ 30%	70 (range, 53-82)	Stomach: 90% GEJ: 10%	Met: 100% 1-2 mets: 87.5% >2 mets: 12.5%	IHC3⁺: 62.5% IHC2⁺/ISH⁺: 37.5%
Liu Cancer Commun 2019 (JACOB subgroup analysis)³¹	Phase III^a (NCT01774786)	Placebo + Trast IV on D1 (loading dose, 8 mg/kg; maintenance dose, 6 mg/kg) Q3W + Cis 80 mg/m² IV Q3W + Cape 1000 mg/m² PO BID for 28 doses (D1-15), Q3W OR 5-FU 800 mg/m² IV every 24 h (D1-5) Q3W	China: 100%	Asian: 100%	81 Cape: 86.4% 5-FU: 16.0%	87.7%/ 12.3%	59 (range, 23-73)	Stomach: 85.2% GEJ: 14.8%	Met: 100% 1-2 mets: 89% >2 mets: 11%	IHC3⁺: 79% IHC2⁺/ISH⁺: 21%
Tabernero Lancet Oncol 2018 (JACOB)³²	Phase III^a (NCT01774786)	Placebo + Trast IV on D1 (loading dose, 8 mg/kg; maintenance dose, 6 mg/kg) Q3W + Cis 80 mg/m² IV Q3W + Cape 1000 mg/m² PO BID for 28 doses (D1-15), Q3W OR 5-FU 800 mg/m² IV every 24 h (D1-5) Q3W	Asia: 37% Japan: 10% North America, Western Europe, Australia: 34% South America, Eastern Europe: 19%	Asian: 47.9% White: 47.7% Other: 3.8%	392	82%/ 18%	61 (IQR, 54-68)	Stomach: 75% GEJ: 25%	Met: 100% 1-2 mets: 77% >2 mets: 23%	IHC3⁺: 67% IHC2⁺/ISH⁺: 33%
Shah J Clin Oncol 2017 (HELOISE)²⁸	Phase III^a (NCT01450696)	Trast IV on D1 (loading dose, 8 mg/kg; maintenance dose, 6 mg/kg) Q3W + Cis 80 mg/m² IV Q3W + Cape 800 mg/m² PO BID for 28 doses over 14 days Q3W	China: 25.8% ROW: 74.1%	Asian: 29.8% White: 60.5% Other: 9.7%	124	76.6%/ 23.4%	60 (range, 26-83)	Stomach: 76.6% GEJ: 23.4%	Met: 100% 1-2 mets: 59.7% >2 mets: 40.3%	IHC3⁺ or IHC2⁺/FISH⁺ (breakdown NR)
Sawaki Gastric Cancer 2012 (ToGA subgroup analysis)²⁹	Phase III^b (NCT01041404)	Trast IV on D1 (loading dose, 8 mg/kg; maintenance dose, 6 mg/kg) Q3W + Cis 80 mg/m² IV D1 Q3W + Cape 1000 mg/m² PO BID for 28 doses (D1-14) Q3W	Japan: 100%	Asian: 100%	51	78.4%/ 21.6%	63 (range, 29-76)	Stomach: 96.1% GEJ: 3.9%	Met: 100% 1-2 mets: 54.9% >2 mets: 45.1%	IHC3⁺/FISH⁺: 31.4% IHC2⁺/FISH⁺: 35.3% IHC3⁺/FISH⁻: 2% IHC3⁺/FISH^unk: 5.9% IHC1⁺/FISH⁺: 19.6% IHC0/FISH⁺: 5.9%
Bang Lancet 2010 (ToGA)⁶	Phase III^b (NCT01041404)	Trast IV on D1 (loading dose, 8 mg/kg; maintenance dose, 6 mg/kg) Q3W + Cis 80 mg/m² IV D1 Q3W + Cape 1000 mg/m² PO BID for 28 doses (D1-14) Q3W OR 5-FU 800 mg/m² IV every 24 h (D1-5) Q3W	Asia: 54.6% Europe: 32.5% Central or South America: 8.9% Other: 3.9% (N = 584)	Asian: 51% White: 39% Black: <1% Other: 9%	294 Cape: 87% 5-FU: 13%	77%/ 23%	Mean 59.4 (SD, 10.8)	Stomach: 80% GEJ: 20%	Met: 97% Locally advanced: 3% 1-2 mets: 52% >2 mets: 48%	IHC3⁺/FISH⁺: 45% IHC2⁺/FISH⁺: 27% IHC3⁺/FISH⁻: 3% IHC3⁺/FISH^unk: 3% IHC1⁺/FISH⁺: 13% IHC0/FISH⁺: 8% IHC^unk/FISH⁺: 2%
Yuki Cancer Chemother Pharmacol 2020 (KSCC/HGCSG/CCOG/Perseus 1501B)²⁷	Phase II (UMIN000017552)	Trast IV on D1 (loading dose, 8 mg/kg; maintenance dose, 6 mg/kg) Q3W + Oxal 130 mg/m² IV D1 Q3W + S-1 80 mg/m² PO BID (D1-14) Q3W	Japan: 100%	Asian: 100%	39	79%/ 21%	66.0 (range, 44-79)	Upper: 36% Middle: 28% Low: 36%	Liver mets: 56% No liver mets: 44%	IHC3⁺: 87% IHC2⁺/FISH⁺: 13%
Rivera Cancer Chemother Pharmacol 2019 (HERXO)³³	Phase II (NCT01503983)	Trast IV on D1 (loading dose, 8 mg/kg; maintenance dose, 6 mg/kg) Q3W + Oxal 130 mg/m² IV D1 Q3W + Cape 1000 mg/m² PO BID (D1-14) Q3W	Spain: 100%	White: 100%	45	82%/ 18%	65 (range, 44-80)	Stomach: 69% GEJ: 31%	Met: 82% Relapsed: 16% Unresectable locally advanced: 2%	IHC3⁺: 73% IHC2⁺: 27%
Takahari Gastric Cancer 2019 (HIGHSOX)³⁴	Phase II (UMIN000017602)	Trast IV on D1 (loading dose, 8 mg/kg; maintenance dose, 6 mg/kg) Q3W + Oxal 130 mg/m² IV D1 Q3W + S-1 40-60 mg/m² PO BID (D1-14) Q3W (40 mg for BSA <1.25 m²; 50 mg for BSA 1.25-1.5 m²; 60 mg for BSA >1.5 m²)	Japan: 100%	Asian: 100%	75	78.7%/ 21.3%	64 (range, 21-75)	Stomach: 85.3% GEJ: 14.7%	Advanced: 100% Mets, median (range): 1 (1-5)	IHC3⁺: 73.3% IHC2⁺/ISH⁺: 26.7%
Miura Gastric Cancer 2018 (WJOG7212G/T-SPACE)³⁵	Phase II (UMIN000008389)	Trast IV on D1 (loading dose, 8 mg/kg; maintenance dose, 6 mg/kg) Q3W + Cis 60 mg/m² IV D8 Q5W + S-1 40-60 mg/m² PO BID (D1-21) Q5W (40 mg for BSA <1.25 m²; 50 mg for BSA 1.25–1.5 m²; 60 mg for BSA >1.5 m²)	Japan: 100%	Asian: 100%	44	77.3%/ 22.7%	64.5 (range, 31-77)	Stomach: 84.1% GEJ: 15.9%	Met: 100% 0-1 mets: 54.5% ≥2 mets: 45.5%	IHC3⁺: 72.7% IHC2⁺/FISH⁺: 27.3%
Ryu Eur J Cancer 2015²⁶	Phase II (NCT01396707)	Trast IV on D1 (loading dose, 8 mg/kg; maintenance dose, 6 mg/kg) Q3W + Oxal 130 mg/m² IV D1 Q3W + Cape 1000 mg/m² PO BID (D1-14) Q3W	South Korea: 100%	Asian: 100%	55	66%/ 34%	57 (range, 29-74)	Stomach or GEJ (breakdown NR)	Met: 82% Recurrent: 14% Inoperable locally advanced: 4% Met sites: Liver: 49% Peritoneum: 27% Lung: 20% Bone: 13% Lymph node: 76%	IHC3⁺: 89% IHC2⁺/FISH⁺: 11%
Kurokawa Br J Cancer 2014 (HERBIS-1)²³	Phase II (UMIN000005739)	Trast IV on D1 (loading dose, 8 mg/kg; maintenance dose, 6 mg/kg) Q3W + Cis 60 mg/m² IV D1 Q3W + S-1 40-60 mg/m² PO BID (D1-14) Q3W (40 mg for BSA <1.25 m²; 50 mg for BSA 1.25-1.5 m²; 60 mg for BSA ≥1.5 m²)	Japan: 100%	Asian: 100%	54	78%/ 22%	66 (range, 34-75)	Stomach or GEJ (breakdown NR)	Unresectable: 94% Recurrent: 6% Met sites: Lymph nodes: 81% Liver: 59% Lung: 9% Peritoneum: 9% Bone: 4% Other: 2%	IHC3⁺: 83% IHC2⁺/FISH⁺: 17%
Gong BMC Cancer 2016 (CGOG1001)³⁶	Phase II (NCT01364493)	Trast IV on D1 (loading dose, 8 mg/kg; maintenance dose, 6 mg/kg) Q3W + Oxal 130 mg/m² IV D1 Q3W + Cape 1000 mg/m² PO BID (D1-14) Q3W	China: 100%	Asian: 100%	51	71%/ 29%	57 (range, 27-78)	Stomach: 65% GEJ: 35%	Met: 86% Locally advanced: 14%	IHC3⁺: 75% IHC2⁺/dual SISH⁺: 25%
Oh Cancer Chemother Pharmacol 2019²⁵	Retrospective	Trast IV on D1 (loading dose, 8 mg/kg, 90-min infusion; maintenance dose, 6 mg/kg, 30-min infusion) Q3W + Cis 60-100 mg/m² IV D1 Q3W + Cape 1000 mg/m² PO BID (D1-14) Q3W OR 5-FU 1000 mg/m² IV every 24 h (D1-5) Q3W	Korea: 100%	Asian: 100%	128 Cape: 96% (3 pts received oxal vs cis) 5-FU: 3.1%	80.5%/ 19.5%	63 (range, 20-87)	Stomach or GEJ (breakdown NR)	Met: 100% 1 met: 60.2% 2 mets: 25.8% ≥3 mets: 14.0%	IHC3⁺: 91.4% IHC2⁺/ISH⁺: 8.6%
Okita Tohoku J Exp Med 2018³⁷	Retrospective	T-XP(cape + cis) (n= 28) Trast IV on D1 (loading dose, 8 mg/kg; maintenance dose, 6 mg/kg) Q3W + Cape 1000 mg/m² PO BID (D1-14) Q3W + Cis 80 mg/m² IV D1 Q3W T-SP(S-1 + cis) (n= 30) Trast IV on D1 (loading dose, 8 mg/kg; maintenance dose, 6 mg/kg) Q3W + S-1 40 mg/m² PO BID (D1-14) Q3W + Cis 60 mg/m² IV D1 Q3W	Japan: 100%	Asian: 100%	28 (T-XP)	89.3%/10.7%	68.5 (range, 44-81)	Stomach: 82.1% GEJ: 17.9%	Inoperable advanced or recurrent: 100%	IHC3⁺: 82.1% IHC2⁺/ISH⁺: 14.3% Unk: 3.6%
Okita Tohoku J Exp Med 2018³⁷	Retrospective		Japan: 100%	Asian: 100%	30 (T-SP)	86.7%/ 13.3%	63.5 (range, 38-74)	Stomach: 76.7% GEJ: 23.3%	Inoperable advanced or recurrent: 100%	IHC3⁺: 83.3% IHC2⁺/ISH⁺: 16.7%
Soularue Bull Cancer 2015¹⁹	Retrospective	Trast IV on D1 (loading dose, 6 mg/kg; maintenance dose, 4 mg/kg) Q3W + mFOLFOX6 Oxal 85 mg/m² IV D1 Q2W + Leucovorin 400 mg/m² IV D1 Q2W + 5-FU bolus 400 mg/m² IV D1 Q2W + 5-FU 2400 mg/m² continuous IV D1 Q2W OR Trast IV on D1 (loading dose, 8 mg/kg; maintenance dose, 6 mg/kg) Q3W + XELOX Oxal 130 mg/m² IV D1 Q3W + Cape 1000 mg/m² PO BID (D1-14) Q3W	France: 100%	NR	34	79%/ 21%	63 (range, 30-82)	GEJ: 71% Stomach: 29%	Met: 100% Mets, median (range): 2 (1-4) 1 met: 64.7% 2 mets: 20.6% >2 mets: 14.7%	IHC3⁺: 88% IHC2⁺/FISH⁺: 12%
Kim BMC Cancer 2021²⁰	Retrospective	Trast IV on D1 (loading dose, 8 mg/kg; maintenance dose, 6 mg/kg) Q3W + Cis 80 mg/m² IV D1 Q3W + Cape 1000 mg/m² PO BID (D1-14) Q3W OR 5-FU 800 mg/m² IV every 24 h (D1-5) Q3W	Korea: 100%	Asian: 100%	47	81%/ 19%	59 (range, 36-83)	Stomach: 100%	Met: 77% Recurrent: 23% Liver mets: 51% No liver mets: 49%	IHC3⁺: 85% IHC2⁺/SISH⁺: 15%
Dijksterhuis Int J Cancer 2020²²	Retrospective	Trast + oxal + cape (n = 73) OR Trast + cis + cape (n = 65) OR Trast + other doublet CTX (n = 29) OR Trast + other CTX (n = 47) OR Trast monotherapy (n = 1)	Netherlands: 100%	White: 100%	215	79.5%/ 21.5%	63 (IQR, 55-69)	Esophagus: 54% GEJ or cardiac: 19.1% Stomach: 27.0%	Met: 100% 1-2 mets: 44% >2 mets: 56%	IHC3⁺ or IHC2⁺/FISH⁺ (breakdown NR)
Li Clin Transl Oncol 2018²¹	Prospective observational	Trast + platinum (cis, oxal) + fluoropyrimidine (5-FU, cape, S-1) (n = 75) Trast + taxane (doce, pacli) + fluoropyrimidine (5-FU, cape, S-1) (n = 20) Trast + monotherapy CTX (n = 10) Trast + iri + cis (n = 2) Trast IV (loading dose, 8 mg/kg; maintenance dose, 6 mg/kg) Q3W	China: 100%	Asian: 100%	107 (75 pts [70%] had fluoropyrimidine + platinum)	77%/ 23%	64 (range, 26-87)	Stomach: 100%	Advanced/met: 100% <2 mets: 35.7% >2 mets: 64.3%	IHC3⁺: 65% IHC2⁺/FISH⁺: 35%
Janjigian Lancet Oncol 2020¹⁵	Phase II (NCT02954536)	Pembro 200 mg IV D1 Q3W + Trast IV on D1 (loading dose, 8 mg/kg in C1; maintenance dose, 6 mg/kg in C2+) Q3W + Oxal 130 mg/m² OR cis 80 mg/m² IV on D1C2+ Q3W + Cape 850 mg/m² PO BID (D1-14) C2+ OR 5-FU 800 mg/m² IV (D1-5) Q2W	USA: 100%	White: 86% Asian: 5% Black/ Hispanic/other: 8%	37 Oxal: 97% Cis: 3% Cape: 65% 5-FU: 35%	78%/22%	60 (IQR, 21-84)	Esophagus: 38% GEJ: 32% Stomach: 30%	Met: 100%	IHC3⁺ or IHC2⁺/FISH⁺: 84% IHC2⁺/FISH⁻ or IHC1⁺ or IHC0: 16% PD-L1⁻ (CPS <1): 35% PD-L1⁺ (CPS ≥1): 38% PD-L1^unkn: 27%
Lee AACR 2021, Abstr. CT174 (HCRN GI17-319)²⁴	Phase II (NCT03783936)	Ave 800 mg IV D1 + Trast IV on D1 (loading dose, 8 mg/kg in C1; maintenance dose, 6 mg/kg in C2+) Q3W + mFOLFOX Oxal 85 mg/m² IV D1 Q2W + Leucovorin 400 mg/m² IV D1 Q2W + 5-FU bolus 400 mg/m² IV D1 Q2W + 5-FU 2400 mg/m² continuous IV D1 Q2W	USA: 100%	NR	NR	NR	NR	Stomach or GEJ (breakdown NR)	Met: 100%	IHC3⁺ or IHC2⁺/FISH⁺ (breakdown NR)
Rha ASCO 2020, Abstr. 3031 Rha ASCO GI 2021, Abstr. 218 (PANTHERA)¹⁷	Phase Ib/II (NCT02901301)	Pembro 200 mg IV D1 Q3W + Trast biosimilar IV on D1 (loading dose, 8 mg/kg; maintenance dose, 6 mg/kg) Q3W (trastuzumab-pkrb) + Cape 1000 mg/m² PO BID (D1-14) Q3W + Cis 80 mg/m² IV D1 Q3W	Korea: 100%	Asian: 100%	43	77%/23%	63 (range, 34-82)	Stomach or GEJ (breakdown NR)	Advanced: 100%	IHC3⁺: 70% IHC2⁺/SISH: 30%
Janjigian ASCO 2021, Abstr. 4013 (KEYNOTE-811)¹⁴	Phase III (NCT03615326)	Placebo + Trast IV on D1 (loading dose, 8 mg/kg; maintenance dose, 6 mg/kg) Q3W + FP 5-FU 800 mg/m² IV (D1-5) Q3W + Cis 80 mg/m² IV on D1 Q3W OR CAPOX Cape 1000 mg/m² PO BID (D1-14) Q3W + Oxal 130 mg/m² IV D1 Q3W OR SOX S-1 40-60 mg/m² PO BID (D1-14) Q3W (40 mg for BSA <1.25 m²; 50 mg for BSA 1.25-1.5 m²; 60 mg for BSA ≥1.5 m²) + Oxal 130 mg/m² IV D1 Q3W	North America, Europe, Israel, Australia: 34% Asia: 30% ROW: 37%	NR	131 CAPOX: 88% FP: 12%	79% 21%	61 (range, 32-83)	Stomach: 68% GEJ: 32%	Met: 100%	IHC3⁺: 79% IHC2⁺/ISH⁺: 21%
		Pembro 200 mg IV D1 Q3W + Trast IV on D1 (loading dose, 8 mg/kg; maintenance dose, 6 mg/kg) Q3W + FP 5-FU 800 mg/m² IV (D1-5) Q3W + Cis 80 mg/m² IV on D1 Q3W OR CAPOX Cape 1000 mg/m² PO BID (D1-14) Q3W + Oxal 130 mg/m² IV D1 Q3W OR SOX S-1 40-60 mg/m² PO BID (D1-14) Q3W (40 mg for BSA <1.25 m²; 50 mg for BSA 1.25-1.5 m²; 60 mg for BSA ≥1.5 m²) + Oxal 130 mg/m² IV D1 Q3W	North America, Europe, Israel, Australia: 31% Asia: 30% ROW: 39%	NR	133 CAPOX: 86% FP: 14% SOX: 0%	84%/16%	62 (range, 19-84)	Stomach: 72% GEJ: 28%	Met: 100%	IHC3⁺: 82% IHC2⁺/ISH⁺: 18%

5-FU, 5-fluorouracil; ave, avelumab; BID, twice daily; BSA, body surface area; C, cycle; cape, capecitabine; CAPOX, capecitabine plus oxaliplatin; cis, cisplatin; CPS, combined positive score; CTX, chemotherapy; D, day; doce, docetaxel; FP, 5-fluorouracil plus platinum; GEJ, gastroesophageal junction; HER2+, human epidermal growth factor receptor 2 positive; IHC, immunohistochemistry; IQR, interquartile range; iri, irinotecan; ISH, in situ hybridization; IV, intravenous; met, metastatic; mets, metastases; NR, not reported; oxal, oxaliplatin; pacli, paclitaxel; PD-L1, programmed death-ligand 1; PO, oral; pembro, pembrolizumab; pts, patients; Q2W, every 2 weeks; Q3W, every 3 weeks; Q5W, every 5 weeks; ROW, rest of the world; SD, standard deviation; SISH, silver-enhanced in situ hybridization; SOX, S-1 plus oxaliplatin; T-SP, trastuzumab plus S-1 plus cisplatin; ToGA, Trastuzumab for Gastric Cancer; trast, trastuzumab; tx, treatment; T-XP, trastuzumab plus capecitabine plus cisplatin; unk, unknown.

Only details on the control arm are reported in this table.

Only details on the experimental arm are reported in this table.