Table 4.
Phase I/II studies related to the efficacy of everolimus treatment with SSAs or studies with everolimus in combination with other agents in NETs
| Study, phase (year) |
n | Treatment (n) | Population (n) [comment] |
PFS | OS | ORR | SD |
|---|---|---|---|---|---|---|---|
| Phase II; Yao et al (2010)[72] |
160 | Statrum 1; Eve, Statrum 2; Eve + Oct |
panNET; Oct-naïve (St 1, n=115), patients on Oct for ≥3 mo (St 2, n=45) | St 1; 9.7 mo, St 2; 16.7 mo |
St 1; 24.9 mo, St 2; not reached (2-yr; 54.7%) |
St 1; 9.6%, St 2; 4.4% |
St 1; 68%, St 2; 80% |
| Phase II: Bajetta et al (2014) [73](2017)[74] |
50 | Eve + Oct | NET; GI (n=11), pancreas (n=14), lung (n=11) | TTP; 33.6 mo | 61.9 mo | 18% | 74% |
| COOPERATE-2, phase II; Kulke et al (2017)[75] |
160 | Eve + Pas (n=79) vs Eve (n=81) | panNET | 16.8 vs 16.6 mo (HR 0.99, p = 0.488) |
Not reached (HR 0.93, p = 0.410) |
20% vs 6% | 57% vs 77% |
| LUNA, Phase II; Ferolla et al (2017)[76] |
124 | Pas (n=41) vs Eve (n=42) vs Eve + Pas (n=41) | NET; lung (n=116), thymus (n=8) |
8.5 vs 12.5 vs 11.8 mo (39% vs 33% vs 59% at 9 mo) |
- | 2.4% in each group (Tumor shrinkage a; 31% vs 49% vs 73%) |
34% vs 31% vs 49% |
| Phase I; Chan et al (2012)[77] |
22 | Eve + Pas | NET; GI (n=14), pancreas (n=4), bronchus (n=2) | 76% at 6 mo 65% at 12 mo |
- | (Tumor shrinkagea; 81%) | 90% |
| CALGB 80701, phase II; Kulke et al (2017)[75] |
150 | Eve + Oct + Bv (n=75) vs Eve + Oct (n=75) | panNET | 16.7 vs 14.0 mo (HR 0.80, p = 0.12) |
36.7 vs 35.0 mo (HR 0.75, p = 0.16) |
31% vs 12% (p = 0.005) |
- |
| Phase I; Dasari et al (2015)[78] |
19 | Eve + Oct + cixutumumab | NET; small bowel (n=6), pancreas (n=4), lung (n=4) | 43.6 weeks | 25.5 mo | (Tumor shrinkage a; 89%) | 89% |
| Phase I; Kim et al (2018)[79] |
13 | Eve + Pas + SIRT | NET; GI (n=6), pancreas (n=3), lung (n=2) | 18.6 mo | 46.3 mo | 46% | 23% |
| Phase I/II; Chan et al (2013)[83] |
43 | Eve 5 or 10 mg + temozolomide | panNET | 15.4 mo | - | 40% | 53% |
| Phase I; Chan et al (2013)[84] |
21 | Eve + sorafenib | NET; GI (n=13), bronchus (n=3), pancreas (n=3) | 79% at 6 mo | - | 6% (Tumor shrinkage a; 62%) | 76% |
| NETTLE, Phase I; Claringbold et al (2015)[85] |
16 | Eve + PRRT | NET; GI (n=11), pancreas (n=5) |
- (No disease progression in 6 mo treatment) |
Not reached (1-yr; 88%, 2-yr; 63%) |
44% | 50% |
| Phase II; Salazar et al (2017)[86] |
62 | BEZ235 (n=31) vs Eve (n=31) | panNET | 8.2 vs 10.8 mo (HR 1.53) | (6-mo; 96.6% vs 90.3%) | 9.7% vs 9.7% | 52% vs 81% |
| Phase II; Oh et al (2012)[87] |
27 | Eve | NF-GEP-NET | 17.1 mo | Not reached | 12% | 88% |
Bv, bevacizumab; Eve, everolimus; GI, gastrointestinal; HR, hazard ratio; NET, neuroendocrine tumor; NF; non-functioning, Oct, octreotide; ORR, objective response rate; OS, overall survival; Pas, pasireotide; panNET, pancreatic neuroendocrine tumor; PFS, progression free survival; PRRT, Peptide Receptor Radionuclide Therapy; SD, stable disease; St, statrum; TTP; time to progression.
a
Included decrease in tumor size less than 30%.