Table 1.
A summary of currently used therapy modalities (systemic and liver loco-regional) for advanced GEP NETs, indicating reference studies for each one, and frequent side effects
| Drug | Study | Population (n) | Design | Primary end-point | Main Outcome | Major side effects |
|---|---|---|---|---|---|---|
| Octreotide LAR | Rinke et al. 2009 [10], PROMID study | Intestinal NETs F/NF (85) | Randomized phase III | PFS | 14.3 months vs 6 months with placebo | Diarrhea, flatulence, cholelithiasis |
| Lanreotide autogel | Caplin et al. 2014 [11], CLARINET study | NF Intestinal/ Pancreatic NETs (204) | Randomized phase III | PFS | Median not reached vs 18 months with placebo | Diarrhea, flatulence, cholelithiasis, hyperglycemia |
| Interferon | Oberg et al. 2012 [15] | GEP NETs, carcinoid syndrome | Review | Clinical and biochemical response, tumor effect | Symptoms relief up to 70%, biochemical response 50–60%, SD up to 70% | Flu-like symptoms, chronic fatigue, liver toxicity, bone marrow suppression, depression, autoimmune-related conditions |
| Everolimus | Yao et al., 2008 [21], RADIANT-1 study | PNET (160) | Single-arm (± sandostatin) phase II | Response rate | 8.7% objective response rate; 84.7% stable disease | |
| Pavel et al., 2011 [23], RADIANT-2 study | Intestinal NETs (420) | Randomized phase III | PFS | 16.4 months vs 11.3 months with placebo | Stomatitis, rash, fatigue, diarrhea, nausea, infections, fever, cytopenia, edema, hyperglycemia, dyspnea, pneumonitis | |
| Yao et al., 2011 [23], RADIANT-3 study | PNETs (410) | Randomized phase III | PFS | 11 months vs 4.6 months with placebo | ||
| Yao et al. 2016 [24], RADIANT-4 study | Lung/Intestinal NETs (302) | Randomized phase III | PFS | 11 months vs 3.9 months with placebo | ||
| Sunitinib | Raymond et al. 2011 | Pancreatic NETs (171) | Randomized phase III | PFS | 11.4 months vs 5.5 months with placebo | Diarrhea, nausea, asthenia, vomiting, fatigue, HTN, neutropenia, stomatitis, palmar-plantar erythrodysesthesia |
| Telotristat ethyl | Pavel et al. 2015 [16], TELESTAR study | Carcinoid syndrome (135) | Randomized phase III | Reduction in daily bowel movements | Mean reduction of 1.7–2.1 BM/day (dose dependent) vs 0.9 with placebo | Nausea, abdominal pain, vomiting, fatigue, infections, increased LFTs |
| PRRT | Strosberg et al. 2017 [33], NETTER-1 trial | Intestinal NETs (229) | Randomized phase III | PFS | PFS at 20 months 65.2% vs 10.8% with SSA alone | Nausea, vomiting, renal impairment, marrow toxicity |
| STZ-5FU | Dilz et al. 2015 [40]; Clewemar et al. 2016 [41] |
pNETs (96) pNETs (133) |
Retrospective | PFS | 19.4 months 23 months |
Nausea, fatigue, kidney toxicity, bone marrow suppression |
| CAPTEM | Strosberg et al. 2011 [45]; Fine et al. 2013 [46] |
pNETs (30) GEP NETs (18) |
Retrospective | PFS | 18 months 14 months |
Fatigue, nausea, myelosuppression, palmar-plantar erythrodysesthesia |
| TACE | Grozinsky-Glasberg et al. 2018 [54] | NETs (57) | Retrospective | PFS | 14 months | Fever, leukocytosis, abdominal pain, nausea, elevated liver enzymes (post embolization syndrome), carcinoid crisis, liver failure, cholecystitis, liver abscess |
| SIRT | Kennedy et al. [55] | NETs (158) | Retrospective | Imaging response | SD 22.7%, PR 60.5%, CR 2.7%, PD 4.9% | Fatigue, nausea, pain, ascites, |
F functioning, NF non-functioning, PFS progression free survival, PRRT peptide receptor radionuclide therapy, STZ-5FU streptozotocin + 5-fluorouracil, CAPTEM capecitabin + temozoomide, TACE trans-arterial chemoembolization, SIRT selective interval radiation therapy, HTN hypertension, LFT liver function tests