Emerging Treatment Options for Gastroenteropancreatic Neuroendocrine Tumors
Abstract
:1. Introduction
2. Innovative PRRT Strategies
3. New Antiangiogenic Agents
4. Immunotherapeutic Agents
5. Future Perspectives
6. Conclusions
Author Contributions
Funding
Conflicts of Interest
References
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Therapeutic Agent | Dosage and Schedule | Patient Population | Number of Patients Enrolled | Objective Responses * (RECIST 1.1) | Reference |
---|---|---|---|---|---|
225Ac-DOTATATE | Systemic infusion every 8 weeks (100 kBq/kg of body weight) | Advanced GEP-NETs stable or progressing on 177Lu-DOTATATE | 32 | ORR: 62% (62% PR; 38% SD) | [17] |
213Bi-DOTATOC | Intra-arterial or systemic infusion every 8 weeks (first cycle: 1GBq; second cycle: 1.5 GBq; third cycle: 2–4 GBq; fourth cycle: as available from the generator) | Advanced NETs with liver metastases progressing on 90Y/177Lu-DOTATOC therapy | 7 | ORR: 50% (17% CR; 33% PR; 50% SD) | [18] |
212Pb-DOTAMTATE | Systemic infusion every 8 weeks (3+3 dose escalation design) | Advanced SSTR+ NETs | 50 | ORR at highest dose cohort: 83% (1 CR; 5 PR) | [20] |
177Lu-DOTA-JR11 | Systemic infusion every 12 weeks (cumulative absorbed bone marrow dose up to 1 Gy) | Advanced, well-differentiated, SSTR+ NETs | 20 | ORR: 45% (5% CR; 40% PR) | [22] |
Therapeutic Regimen | Molecular Target(s) | Clinical Phase | Patient Population | Sample Size | Primary Outcome | Identifier |
---|---|---|---|---|---|---|
Cabozantinib | c-MET, VEGFR2, AXL, KIT, TIE2, FLT3, RET | III | Advanced progressive NETs | 395 | PFS | NCT03375320 |
Axitinib + Octreotide LAR vs. Placebo + Octreotide LAR | VEGFR 1-3 | II/III | Advanced, progressive, G1/G2 NETs of extra-pancreatic origin | 255 | PFS | NCT01744249 |
Lenvatinib + Everolimus | VEGFR 1-3, FGFR 1-4, IT, RET, PDGFR-alpha | II | Advanced progressive carcinoid tumors | 32 | ORR | NCT03950609 |
Nintedanib | VEGFR 1-3, PDGFR-α and -β, FGFR 1-3, FLT3, SRC | II | Advanced, G1/G2 NETs of extra-pancreatic origin | 30 | PFS | NCT02399215 |
Famitinib | c-KIT, VEGFR2-3, PDGFR, FLT1, FLT3 | II | Advanced, G1/G2 GEP-NETs | 53 | ORR | NCT01994213 |
Regorafenib | VEGFR 1-3, PDGFRβ, KIT, RET, RAF-1 | II | Advanced, progressive carcinoid or panNET | 48 | PFS | NCT02259725 |
Anlotinib | VEGFR2/3, FGFR1-4, PDGFR-α and -β, c-KIT, RET | II | G3 advanced GEP-NETs | 60 | PFS | NCT03457844 |
Pazopanib + temozolomide | VEGFR 1-3, PDGFR-α and -β, c-KIT | I/II | Advanced panNETs | 29 | MTD | NCT01465659 |
Evofosfamide (TH-302) + Sunitinib | DNA + VEGFR-1-3, PDGFR-α and -β, c-KIT, FLT-3, CSF1R | II | Advanced, G1/G2, treatment-naïve panNETs | 43 | ORR | NCT02402062 |
Therapeutic Agent | Dosage and Schedule | Patient Population | Number of Patients | Objective Responses (RECIST 1.1) | Reference |
---|---|---|---|---|---|
Pembrolizumab | 10 mg/kg every 2 weeks | Advanced PD-L1+ carcinoids or panNETs | 41 | ORR: 12% (carcinoids); 6.3% (panNETs) | [36] |
Pembrolizumab | 200 mg every 3 weeks | Advanced, well-differentiated NETs | 107 | ORR: 3.7% | [37] |
Pembrolizumab | 200 mg every 3 weeks | Advanced G3 NETs/NECs (Ki-67 > 20%) progressing on platinum-based chemotherapy | 29 | ORR: 3.4% | [39] |
Spartalizumab | 400 mg every 4 weeks | Advanced thoracic/GEP-NETs and GEP-NECs | 116 | ORR: 7.4% (NETs); 4.8% (NECs) | [40] |
Avelumab | 10 mg/kg every 2 weeks | Advanced G3 NECs | 29 | ORR: 6.9% (by irRECIST criteria) | [41] |
Ipilimumab and Nivolumab | Ipilimumab 1 mg/kg every 6 weeks; Nivolumab 240 mg every 2 weeks | Advanced, any grade NETs (excluding panNETs) | 32 | ORR: 25% | [42] |
Ipilimumab and Nivolumab | Ipilimumab 1 mg/Kg every 3 weeks for four doses and Nivolumab 3 mg/Kg, followed by Nivolumab 3 mg/Kg every 2 weeks for up to 96 weeks | Advanced, any grade NETs | 29 | ORR: 24% | [43] |
Durvalumab and Tremelimumab | Durvalumab 1500 mg every 4 weeks for 12 months, and Tremelimumab 75 mg every 4 weeks up to 4 doses/cycles | Cohort 1: well-moderately differentiated lung NETs Cohort 2: G1/G2 gastrointestinal NETs; Cohort 3: G1/2 panNETs Cohort 4: G3 GEP-NENs | 126 | ORR: 7.4% (cohort 1); 0% (cohort 2); 6.3% (cohort 3); 9.1% (cohort 4) (by irRECIST criteria) | [44] |
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Cives, M.; Pelle’, E.; Strosberg, J. Emerging Treatment Options for Gastroenteropancreatic Neuroendocrine Tumors. J. Clin. Med. 2020, 9, 3655. https://doi.org/10.3390/jcm9113655
Cives M, Pelle’ E, Strosberg J. Emerging Treatment Options for Gastroenteropancreatic Neuroendocrine Tumors. Journal of Clinical Medicine. 2020; 9(11):3655. https://doi.org/10.3390/jcm9113655
Chicago/Turabian StyleCives, Mauro, Eleonora Pelle’, and Jonathan Strosberg. 2020. "Emerging Treatment Options for Gastroenteropancreatic Neuroendocrine Tumors" Journal of Clinical Medicine 9, no. 11: 3655. https://doi.org/10.3390/jcm9113655