A phase II trial of Everolimus plus Octreotide LAR as first-line treatment for patients with previously untreated, well-differentiated gastroenteropancreatic NETs and NETs of lung origin, both functioning and not functioning, demonstrated an overall response rate of 18% [ 2% complete response and 16% partial response ], with a disease control rate of 92%; the responses obtained were generally durable ( more than 6 months ).
The efficacy of Everolimus in patients with well-differentiated ( G1 or G2 ) advanced NET of gastrointestinal ( GI ) or lung origin was also evaluated in the landmark RADIANT 4 trial, a prospective, multicenter, randomized, double-blind, placebo-controlled, phase III study.
Patients received Everolimus 10 mg/day ( n = 205 ) or placebo ( n = 97 ) plus best supportive care.
In total, 175 patients had GI NETs and 90 had lung disease.
According to centralized analysis, patients on Everolimus showed an almost 3-fold longer median progression-free survival ( PFS ) than those assigned to the control group ( 11.0 versus 3.9 months, hazard ratio, HR, 0.48; 95% CI, 0.35–0.67; p less than 0.00001 ).
These findings were confirmed at the local evaluation ( 14.0 versus 5.5 months ) and were observed in all the analyzed subgroups, including those with pulmonary disease and patients with GI NETs.
However, when patients with better prognoses ( appendix, caecum, jejunum, ileum, duodenum, and NETs of unknown primary ) are compared with those with worse prognoses ( lung, stomach, rectum, and colon except caecum ), a better hazard ratio for progression or death was observed for patients with worse prognosis ( 0.43 for Everolimus versus placebo ) and in those with moderately-differentiated NETs G2 patients ( 0.49 for Everolimus versus placebo ).
On the other hand, hazard ratio for progression or death in the ‘better prognosis’ subgroup was 0.63 for Everolimus versus placebo, and hazard ratio in patients with well-differentiated NETs G1 was 0.57.
The rate of tumor shrinkage was 64% in the Everolimus group and 26% in the placebo group.
Disease control rate, assessed according to the Response Evaluation Criteria in Solid Tumors ( RECIST ) criteria version 1.0, was 82.4% and 64.9%, respectively. ( Xagena )
Pusceddu S et al, Ther Adv Med Oncol 2017; 9: 183–188