Table 1.
Principal prospective phase III trials of unresectable, recurrent GEP-NETs
| Study | Study design | Setting | Treatment and dose | No. of patients | Primary endpoint | Outcome of primary endpoint | HR | OS |
|---|---|---|---|---|---|---|---|---|
| Somatostatin analogs | ||||||||
| PROMID Rinke A et al. (5,15) |
Phase III | Midgut or unknown origin NET (Functional and non-functional) | Octreotide LAR 30 mg every 28 days vs. placebo |
N = 85 42 vs. 43 |
TTP | OCT: 14.3 m vs. placebo: 6.0 m | 0.34 (0.20–0.59) P < 0.001 |
84.7 vs. 83.7 m |
| CLARINET Martyn E et al. (6,19) |
Phase III | Ki67 < 10% enteropancreatic or unknown origin NET (non-functioning) | Lanreotide LAR vs. placebo |
N = 204 101 vs. 103 |
PFS | NR vs. 18 0.0 m (32.8 vs. 18.0 in open-label extension study) |
0.47 (2.1–24.0) P < 0.001 |
Not reported |
| Molecularly targeted agents | ||||||||
| SUN1111 Raymond E et al. (25,31) |
Phase III | Progressive disease pancreatic NET |
Sunitinib vs. placebo |
N = 171 86 vs. 85 |
PFS | 11.4 m vs. 5.5 m | 0.42 (0.26–0.66) P = 0.0001 |
38.6 vs. 29.1 m |
| RADIANT3 Yao JC et al. (38,39) |
Phase III | Progressive disease pancreatic NET |
Everolimus vs. placebo | 207 vs. 203 | PFS | 11.0 vs. 4.6 m | 0.35 (0.27–0.45) P < 0.0001 |
44.0 vs. 37.7 m |
| RADIANT4 Yao JC et al. (40) |
Phase III | Progressive disease lung or GI NET |
Everolimus vs. placebo | 205 vs. 97 | PFS | 11 vs 3.9 m | 0.48 (0.35–0.67) P < 0.001 |
Not reported |
| SANEP-p Xu J et al. (30) |
Phase III | Progressive disease pancreatic NET |
Surufatinib vs. placebo | 113 vs. 59 | 10.9 vs 3.7 m | 0.49 (0.32–0.76) P = 0.0011 |
Not reported | |
| SANEP-ep Xu J et al. (36) |
Phase III | Progressive disease extrapancreatic NET |
Surufatinib vs. placebo | 129 vs. 69 | 9.2 vs. 3.8 m | 0.33 (0.22–0.50) P < 0.001 |
Not reported | |
| Cytotoxic anticancer agents | ||||||||
| STZ study Moertel CG et al. (45) |
Phase III | pancreatic NET | STZ + doxorubicin vs. STZ + 5-FU vs. chlorozotocin |
N = 105 38 vs. 34 vs. 33 |
OS | 2.2 vs. 1.5 vs. 1.4 years | Not reported | 2.2 vs. 1.5 vs. 1.4 years |
| PRRT | ||||||||
| NETTER-1 (69) | Phase III | Midgut NET progressive to SSA |
PRRT (177Lu-Dotate) vs. Octreotide LAR 60 mg |
N = 229 116 vs. 113 |
PFS | NR vs. 8.4 m |
0.21 (0.13–0.33) | OS data immature |
*Include subgroup analysis.
NET, neuroendocrine tumor; n, number of patients; HR, hazard ratio; RR, response rate; PFS, progression free survival; TTP, time to progression; OS, overall survival; m, months; STZ, streptozocin; 5-FU, 5-fluorouracil; DOX, doxorubicin; PRRT, peptide receptor radionuclide therapy; NR, not reached; −, no data.