Advances in immunology and immunotherapy for mesenchymal gastrointestinal cancers

Li, Bo; Chen, Hui; Yang, Shaohua; Chen, Feng; Xu, Liangliang; Li, Yan; Li, Mingzhe; Zhu, Chengming; Shao, Fangyuan; Zhang, Xinhua; Deng, Chuxia; Zeng, Leli; He, Yulong; Zhang, Changhua

doi:10.1186/s12943-023-01770-6

Molecular Cancer

Table 3 The therapeutic efficacy of ICIs in GIST in published literatures

From: Advances in immunology and immunotherapy for mesenchymal gastrointestinal cancers

Year	Country	Phase	ICIs	Other drugs	Cases	GIST Inclusion Criteria	Key findings	Ref
2014	USA	Ib	Ipilimumab	Dasatinib	8	Failure of imatinib and sunitinib	3 GISTs achieved durable response per Choi criteria	[228]
2017	USA	Ib	Ipilimumab	Dasatinib	20	Advanced/unresectable GIST, failed to imatinib and sunitinib	13 GISTs were evaluable. 7 PR, 3 SD and 3 PD were found per Choi criteria. Synergy was not observed	[229]
2017	USA	I	Ipilimumab	Imatinib	12	Metastatic or unresectable GIST, refractory to standard therapies	1 WT gastric GIST had PR. 9 heavily pretreated GIST had no response. Synergy was not observed	[230]
2017	USA	I	Multiple	NA	9	Metastatic or unresectable advanced GIST	3 GIST patients showed SD (33%), while 1 patient showed hyper-progression after receiving ICIs	[231]
2017	France	II	Pembrolizumab	Metronomic CP	NA	Advanced GIST	The 6-month non-progression rate was 11.1%. PD1 inhibition had limited activity in advanced GIST	[232, 233]
2018	France	II	Pembrolizumab	Metronomic CP	10	Advanced GIST	The 6-month non-progression rate was 11.1%. PD1 inhibition had limited efficacy in advanced GIST, due to infiltrated macrophage and activated IDO1	[34]
2019	USA	II	Nivolumab Ipilimumab	NA	29	Advanced/metastatic GISTs refractory to at least imatinib	For nivolumab monotherapy, 7/15 GIST had SD; For combination therapy, 1/12 had PR, 2/12 had SD	[234]
2020	USA	NA	Nivolumab	NA	1	A metastatic WT GIST refractory to multiple TKIs	1 WT GIST patient showed durable response to nivolumab, progressed after 33.5 months	[235]
2020	USA	II	Nivolumab Ipilimumab	NA	18	GISTs refractory to ≥ 1 regimen(s)	Both nivolumab monotherapy and combination therapy had 9 patients, but all showed no response	[236]
2022	USA	II	Nivolumab Ipilimumab	NA	35	Advanced/metastatic GISTs refractory to at least imatinib	For nivolumab monotherapy, 10/19 had SD, For combination therapy, 1/16 had CR and 4/16 had SD	[237]
2022	India		Pembrolizumab	NA	2	Advanced/metastatic GIST	No response to pembrolizumab monotherapy	[238]

Abbreviations: GIST Gastrointestinal stromal tumor, ICIs Immune checkpoint inhibitors, CP Cyclophosphamide, WT wild type, PD1 Programmed cell death protein 1, CR Complete response, PR Partial response, PD Progressive disease, SD Stable disease, NA Not applicable, IDO Indoleamine 2,3-dioxygenase

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