Background
Phase III, double-blind, placebo-controlled RCT with optional open-label extension. 77 patients with metastatic and/or unresectable, SSTR-positive typical carcinoid (TC; n=45) or atypical carcinoid (AC; n=32) of bronchopulmonary origin. Randomized 2:1 (LAN:placebo). Enrollment was stopped early (77 of planned 158 patients) due to slow accrual attributed to guideline updates recommending SSA as first-line for bronchopulmonary NETs during the study period, which made placebo-controlled recruitment untenable. The original primary endpoint (PFS in the double-blind phase) was subsequently adapted.
Interventions and follow up
Arm A: Lanreotide autogel/depot (LAN) 120 mg SC q28d + best supportive care (n=51)
Arm B: Placebo SC q28d + best supportive care (n=26); eligible for open-label LAN after the double-blind phase
Primary endpoint: Progression-free survival (PFS) by central radiologic review (RECIST 1.1)
Median follow-up: NR
Arm B: Placebo SC q28d + best supportive care (n=26); eligible for open-label LAN after the double-blind phase
Primary endpoint: Progression-free survival (PFS) by central radiologic review (RECIST 1.1)
Median follow-up: NR
Results
Combined DB+OL mPFS (all LAN recipients, adapted primary): 16.6 months (95% CI 11.3–21.9)
TC subgroup: 21.9 months (95% CI 12.8–NC)
AC subgroup: 13.8 months (95% CI 5.4–16.6)
DB phase only — LAN vs placebo mPFS: 16.6 vs 13.6 months (not statistically significant; no formal P value)
TC subgroup: 21.9 months (95% CI 12.8–NC)
AC subgroup: 13.8 months (95% CI 5.4–16.6)
DB phase only — LAN vs placebo mPFS: 16.6 vs 13.6 months (not statistically significant; no formal P value)
Adverse events
Overall: LAN was well tolerated; adverse events were consistent with known somatostatin-analog class effects, and quality of life did not deteriorate with LAN during the study.
Gastrointestinal / injection-site: Gastrointestinal symptoms and injection-site reactions, as expected for the SSA class; grade breakdown NR.
Gastrointestinal / injection-site: Gastrointestinal symptoms and injection-site reactions, as expected for the SSA class; grade breakdown NR.
Conclusions
SPINET is the largest prospective study of SSA therapy in SSTR-positive bronchopulmonary NETs. Despite early enrollment termination and an underpowered comparison, results suggest clinical benefit — particularly in typical carcinoid (mPFS 21.9 months) — though no statistically significant difference was achieved in the double-blind placebo-controlled phase.
Key Limitations
Key Limitations: The trial closed early at 77 of 158 planned patients, leaving the double-blind comparison underpowered. The primary endpoint was adapted mid-study to a combined double-blind plus open-label analysis, which lacks a concurrent control. Small subgroup sizes (TC n=45, AC n=32) limit precision. No OS data. Findings apply specifically to SSTR-positive bronchopulmonary carcinoids and may not generalize to SSTR-negative or higher-grade lung NETs.
Clinical Context
Somatostatin analogs are an established first-line antiproliferative option for SSTR-positive, well-differentiated NETs (PROMID, CLARINET in GEP-NET). SPINET extends supportive evidence to bronchopulmonary carcinoids, where SSAs are commonly used off the strength of these GEP-NET data and ENETS recommendations. For progressive lung NETs, everolimus (RADIANT-4) and PRRT remain alternative options.
References