Background
Phase III RCT included 302 patients with advanced (unresectable or metastatic), non-functional, well-differentiated (grade 1 or 2) neuroendocrine tumors of the lung or gastrointestinal tract (extra-pancreatic) with documented progression.
Interventions and follow up
Arm A: Everolimus 10 mg oral daily
Arm B: Placebo (both with best supportive care; 2:1 randomization)
Primary endpoint: PFS
mFollow up: 21 mo
Arm B: Placebo (both with best supportive care; 2:1 randomization)
Primary endpoint: PFS
mFollow up: 21 mo
Results
mPFS: 11.0 vs 3.9 mo, arm A vs B (HR 0.48; 95% CI 0.35-0.67; P<.00001)
Interim OS: HR 0.64 (95% CI 0.40-1.05; P=.037, not crossing significance boundary)
Interim OS: HR 0.64 (95% CI 0.40-1.05; P=.037, not crossing significance boundary)
Adverse events
Common grade ≥3 (arm A): stomatitis, diarrhea, infections, anemia, fatigue
Pulmonary: non-infectious pneumonitis 13% in arm A (1% grade ≥3)
Discontinuation: due to adverse events 12% vs 3%, arm A vs B
Pulmonary: non-infectious pneumonitis 13% in arm A (1% grade ≥3)
Discontinuation: due to adverse events 12% vs 3%, arm A vs B
Conclusions
Everolimus significantly prolonged PFS versus placebo in advanced, progressive, non-functional lung and GI neuroendocrine tumors, with a manageable safety profile.
Key Limitations
OS difference did not reach statistical significance. Heterogeneous primary sites (lung and varied GI). Class-related toxicities (stomatitis, pneumonitis, hyperglycemia) require monitoring and may limit tolerability.
Clinical Context
FDA approved everolimus for progressive, well-differentiated, non-functional GI and lung NETs (2016). ESMO recognizes everolimus as a treatment option for advanced progressive non-functional GI and lung NETs.
References