Table 2.
Relevant clinical studies of LAN Autogel® in GEP-NENs
| Study | Type of the study | Patients | Aim of the study | Results |
|---|---|---|---|---|
| Ruszniewski et al53 | 6-month, open, non-controlled, multicenter, dose-titration study | 71 patients affected by CS treated with LAN. The dose for the first 2 injections was 90 mg. Subsequent doses could be titrated (60 mg, 90 mg, 120 mg) according to symptom response | Efficacy and safety of 28-day PR-LAN in the treatment of CS | Symptom frequency decreased further after the second and third injections. In 6 months, flushing and diarrhea had significantly decreased from baseline. Median urinary 5-HIAA and CgA levels decreased by 24% and 38%, respectively |
| Bajetta et al44 | Phase III, multicenter, randomized trial | 60 patients randomized; 46 completed the study. Comparison between LAN Autogel 120 mg/6 weeks vs LAN microparticles 60 mg/3 weeks | Efficacy of LAN Autogel vs LAN microparticles in sporadic, well-differentiated NENs with a low grade of malignancy | LAN Autogel was not inferior to LAN microparticles for tumor markers (55% and 59%, respectively) and tumor size reduction (68% and 66%, respectively) |
| Khan et al58 | Retrospective study (9 years) | 69 patients treated (initial dose) with LAN 60 mg/28 days (23 patients), 90 mg/28 days in 36 patients and 120 mg in 7 patients | Clinical response and tolerance of LAN in metastatic midgut NENs and CS | 94% of patients achieved symptomatic response at first follow-up visit. 46% had loss of symptomatic response, but 44% of these achieved control increasing LAN dose. Overall, symptoms were controlled with LAN in 74% of patients. 26% required additional treatment despite good initial response; 30% showed radiological progression |
| Bianchi et al45 | Retrospective study (4 years) | 23 patients receiving LAN Autogel (120 mg) every 28 days | Relief of disease symptoms, behavior of tumor markers response rate in terms of time to tumor progression, and safety and tolerability of LAN in metastatic well-differentiated NENs | Improvement of flushing and diarrhea in 85.7% and 55.6% of patients, respectively. Complete, partial, or no-changed response in the tumor markers behavior in 42.9%, 22.9%, and 17.1% of cases, respectively. Tumor partial regression: 8.7%; stable disease: 65.3%; tumor progression: 26.0%. No severe adverse reaction |
| Martín-Richard et al46 | Multicenter, open-label, Phase II trial | 30 patients receiving LAN Autogel (120 mg) every 28 days | PFS, response rate, tumor biomarkers, symptom control, QoL, and safety in well-differentiated NENs | PFS time: 12.9 months; disease stabilization: 89% of patients; partial response: 4% of cases. No deterioration in QoL. Treatment-related adverse events (most frequently diarrhea and asthenia): 63% |
| Palazzo et al50 | Retrospective study | 68 patients with well-differentiated NENs treated with LAN | To identify factors associated with tumor control in a group of patients with well-differentiated, malignant GEP-NENs treated with LAN | Tumor progression in 57.4%. Median PFS was 29 months. Ki-67 index of up to 5%, pretreatment stability, and hepatic tumor load of up to 25% were significantly associated with disease stability under LAN therapy |
| Vinik et al54 | 16-week, randomized, double-blind, Phase III trial | LAN 120 mg/28 days, n=59; placebo, n=56 | Efficacy of LAN 120 mg/4 weeks in treatment of CS | The percentage days with rescue OCT use is significantly lower in the LAN vs placebo (33.7% vs 48.5%) |
| Caplin et al47 | 96-week, randomized, double-blind, placebo-controlled, multinational study (CLARINET) | LAN Autogel 120 mg/28 days, n=101; placebo, n=103 | PFS, overall survival, QoL, and safety in SSAs-positive, G1 or G2 NENs and documented disease-progression status | PFS at 24 months was 65.1% for LAN and 33.0% for placebo group. No significant differences in QoL or overall survival. The most common treatment-related adverse event was diarrhea (in 26% of the patients in the LAN group and 9% of those in the placebo group) |
| Orlewska et al59 | National, multicenter, non-interventional, observational study (LANRONET) | 52 patients receiving LAN 120 mg/28 days | To examine characteristics and treatment patterns of symptomatic NEN patients treated with LAN Autogel 120 mg for at least 3 months before inclusion, administered as part of routine clinical practice | Primary tumors were GEP-NENs (51.2%); all tumors were metastatic. Most commonly reported symptoms were flushing and diarrhea (55.8%). During the 12-month observation, 28% received LAN Autogel |
| Ruszniewski et al55 | International, open-label, observational study (SYMNET) | 273 patients | Satisfaction with diarrhea control; severity, change in symptoms, and impact on daily life of diarrhea; and satisfaction with flushing control | 76% were “completely” or “rather” satisfied with diarrhea control; 79% had improvement in diarrhea with LAN. 75% were unconcerned about the impact of diarrhea on daily life. Satisfaction with flushing control was 73% |
| Caplin et al49 | Open-label extension of CLARINET study | 88 patients. LAN, n=41; placebo, n=47 | Long-term safety and additional efficacy | Patients continuing LAN reported fewer adverse events than core study. Placebo-to-LAN switch patients reported similar adverse effects |
| Faggiano et al51 | Observational multicenter study | 106 patients with a histologically confirmed GEP or thoracic NENs or unknown primary NENs, initially treated with LAN Autogel (120 mg/28 days) or OCT LAR (30 mg/28 days). The initial SSA dose has been subsequently changed in 14 patients. OCT was switched to LAN in 6 cases | Evaluate the efficacy of long-acting SSAs in NENs according to Ki-67 index | Tumor response in 11%, stability in 58%, and progression in 31%. No differences between G1 and G2 NENs. PFS was longer but not significantly different in G1 than G2 NENs. The median PFS was significantly longer in NENs showing Ki-67 <5% than in those showing Ki-67 ≥5% |
Abbreviations: 5-HIAA, 5-hydroxyindoleacetic acid; CgA, chromogranin A; CS, carcinoid syndrome; GEP, gastroenteropancreatic; LAN, lanreotide; NENs, neuroendocrine neoplasms; OCT, octreotide; PFS, progression-free survival; PR, prolonged release; QoL, quality of life; SSAs, somatostatin analogs; LAR, long acting repeatable.