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Copyright ©The Author(s) 2023.
World J Gastroenterol. Jul 14, 2023; 29(26): 4174-4185
Published online Jul 14, 2023. doi: 10.3748/wjg.v29.i26.4174
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.
PembrolizumabI16pNET6.34.521.0[29]
II29 (14 GI, 10 pancreas)GI-NEN, pNEN3.42.04.7[30]
II107 (83 GEP)WD NETs3.74.124.2[31]
ToripalimabIb40 (23 GI, 9 pancreas)GI-NEN13.02.57.8[32]
pNEN22.0
NivolumabII185 (93 GEP)GEP-NEC7.01.87.2[33]
SpartalizumabII95 NETs (32 GI, 33 pancreas); 21 GEP-NECsGI NET3.13.8Not estimable[34]
pNET3.0
GEP-NEC4.81.86.8
AvelumabII27 (21 GEP)GEP-NET--3.314.2[35]
Nivolumab + Ipilimumab--34 (21 from digestive organs)NENs14.71.05.0 (from treatment initial); 14.0 (from diagnosis)[36]
II32 (15 GI)Non-pNETs25.04.011.0[37]
II19 (9 from digestive organs)High-grade NENs26.02.08.7[38]
II185 (93 GEP)GEP-NEC14.91.95.8[33]
--11Metastatic EP-NEC (mainly of GEP origin)--8.5Not reached[39]
Durvalumab + TremelimumabII123 (31 GI, 32 pancreas, 33 GEP)G1/G2 GI-NETs05.829.5[40,41]
G1/G2 pNETs6.35.523.8
G3 GEP-NENs9.12.45.9
Atezolizumab + BevacizumabII40 (20 pNET, 20 non-pNET)pNET20.019.630.1[44,45]
Non-pNET15.014.9Not reached
Pembrolizumab + LenvatinibII20 (10 GI)GI-NEN10.010.0--[46]
Pembrolizumab + Irinoteca/PaclitaxelII22 (16 GI)GI-NEC9.02.04.0[47]
Nivolumab + TezolomideII15 (12 evaluable and 7 GEP)GEP-NET25.0----[48]
Nivolumab + Cisplatin/CarboplatinII38 (31 GEP)G3 NENs54.15.713.9[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.
Table 2 Ongoing clinical trials related to immune checkpoint inhibitors in neuroendocrine neoplasms of the digestive system
Indentifier of Clinical Trails
Intervention
Study phase
Primary outcome measures
Estimated or actual enrollment
Trial status
Estimated study completion date
Condition related to NENs of the digestive system
NCT04079712Nivolumab + Ipilimumab + CabozantinibIIoverall response rate30Active, not recruitingOctober 2023NECs: Excluding SCLC and MCC
NCT03980925Nivolumab + Platinum-doublet chemotherapyIIOS at 12 mo38Active, not recruitingDecember 2023G3 NENs: GEP or unknown primary site
NCT04197310Cabozantinib + NivolumabIIORR35Active, not recruitingDecember 2023WD-NET: Non-pancreatic (i.e., carcinoid) origin
NCT03290079Pembrolizumab + LenvatinibIIORR28Active, not recruitingJanuary 2024NETs: WD small bowel or colon origin, including unknown primary, excluding pNENs
NCT04400474Cabozantinib + AtezolizumabIIORR93Active, not recruitingMarch 2024WD G1/2 NET: Digestive system; G3 NEN: Excluding SCLC
NCT04579757Surufatinib + TislelizumabIb/IIDLT, ORR135Active, not recruitingJune 2024G1/2 NETs: Thoracic or GEP origins
NCT04525638Nivolumab + 177Lu-DOTATATEIIoverall response rate30RecruitingSeptember 2024G3 NET or NEC of GEP, lung, and unknown primary site
NCT05058651Atezolizumab + Platinum drug (cisplatin or carboplatin) + EtoposideII/IIIOS189RecruitingOctober 2024NEC: Extrapulmonary
NCT05113355Chidamide + SintilimabIIORR23RecruitingNovember 2024High-grade NEN, advanced and metastatic
NCT04969887Nivolumab + IpilimumabIICBR, 6 mo PFS240RecruitingDecember 2024NECs and G3 NETs: Independent of primary site, excluding SCLC
NCT04701307Dostarlimab + NiraparibII6 mo PFS, 3 mo ORR48Active, not recruitingMay 2025NECs: Excluding prostate origin
NCT03475953Avelumab + RegorafenibI/IIPhase I: Recommended dose of regorafenib; Phase II (cohort G): CR or PR747 (only cohort G consists of GEP-NETs)RecruitingDecember 2025G2/3 GEP-NETs
NCT05746208Lenvatinib + PembrolizumabIIORR29Not yet recruitingJuly 2027WD G3 NET: GIsite and pancreas primary
NCT05289856Avelumab + CabozantinibIIDCR, CR, PR, SD30RecruitingDecember 2025G3 NET: Excluding MCC and SCLC
NCT05627427Surufatinib + SintilimabIIPFS60RecruitingDecember 2024G3 NET and NEC: Metastatic and advanced
NCT05262556NP-101 (TQ Formula) + Nivolumab + IpilimumabICR, PR, SD10RecruitingDecember 2024GEP-NET, GEP-NEC: Poorly differentiated
CR: Complete response; CBR: Clinical benefit rate; DCR: Disease control rate; DLT: Dose-limiting toxicity; ORR: Objective response rate; OS: Overall survival; PFS: Progression-free survival; PR: Partial response; 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; GI: gastrointestinal; G1, 2, 3: Grade 1, 2, 3.