Progress in immunotherapy for neuroendocrine neoplasm of the digestive system

Table 1 Clinical trials mentioned in the review

Intervention	Study phase	Actual enrollment	NEN type of the digestive system	ORR (%)	mPFS (mo)	mOS (mo)	Ref.
Pembrolizumab	I	16	pNET	6.3	4.5	21.0	[29]
	II	29 (14 GI, 10 pancreas)	GI-NEN, pNEN	3.4	2.0	4.7	[30]
	II	107 (83 GEP)	WD NETs	3.7	4.1	24.2	[31]
Toripalimab	Ib	40 (23 GI, 9 pancreas)	GI-NEN	13.0	2.5	7.8	[32]
			pNEN	22.0
Nivolumab	II	185 (93 GEP)	GEP-NEC	7.0	1.8	7.2	[33]
Spartalizumab	II	95 NETs (32 GI, 33 pancreas); 21 GEP-NECs	GI NET	3.1	3.8	Not estimable	[34]
			pNET	3.0
			GEP-NEC	4.8	1.8	6.8
Avelumab	II	27 (21 GEP)	GEP-NET	--	3.3	14.2	[35]
Nivolumab + Ipilimumab	--	34 (21 from digestive organs)	NENs	14.7	1.0	5.0 (from treatment initial); 14.0 (from diagnosis)	[36]
	II	32 (15 GI)	Non-pNETs	25.0	4.0	11.0	[37]
	II	19 (9 from digestive organs)	High-grade NENs	26.0	2.0	8.7	[38]
	II	185 (93 GEP)	GEP-NEC	14.9	1.9	5.8	[33]
	--	11	Metastatic EP-NEC (mainly of GEP origin)	--	8.5	Not reached	[39]
Durvalumab + Tremelimumab	II	123 (31 GI, 32 pancreas, 33 GEP)	G1/G2 GI-NETs	0	5.8	29.5	[40,41]
			G1/G2 pNETs	6.3	5.5	23.8
			G3 GEP-NENs	9.1	2.4	5.9
Atezolizumab + Bevacizumab	II	40 (20 pNET, 20 non-pNET)	pNET	20.0	19.6	30.1	[44,45]
			Non-pNET	15.0	14.9	Not reached
Pembrolizumab + Lenvatinib	II	20 (10 GI)	GI-NEN	10.0	10.0	--	[46]
Pembrolizumab + Irinoteca/Paclitaxel	II	22 (16 GI)	GI-NEC	9.0	2.0	4.0	[47]
Nivolumab + Tezolomide	II	15 (12 evaluable and 7 GEP)	GEP-NET	25.0	--	--	[48]
Nivolumab + Cisplatin/Carboplatin	II	38 (31 GEP)	G3 NENs	54.1	5.7	13.9	[49,50]

WD: Well-differentiated; NET: Neuroendocrine tumor; NEN: Neuroendocrine neoplasm; NEC: Neuroendocrine carcinoma; GEP: Gastroenteropancreatic; SCLC: Small cell lung cancer; MCC: Merkel cell carcinoma; pNET: Pancreas NET; ORR: Objective response rate; mOS: Median overall survival; mPFS: Median progression-free survival; EP-NEC: Extrapulmonary neuroendocrine carcinoma.