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4089 Background: In the CLARINET core study, lanreotide Autogel (LAN) 120 mg deep sc monthly significantly improved PFS vs PBO in metastatic grade-1/2 enteropancreatic NETs. An interim analysis of patients with stable disease (SD) in the core study continuing LAN in the open-label extension (OLE, of which safety was primary objective) showed continued antitumor effects. Here, we report final LAN PFS analyses for subgroups according to tumor origin and prior therapy. Methods: In the core study, patients with metastatic well/moderately differentiated non-functioning (N-F) enteropancreatic NETs, Ki-67 <10%, no prior somatostatin-analog treatment and no other prior medical therapies in the previous 6 months were randomized to LAN 120 mg (n=101) or PBO (n=103) for 96 weeks or until death/progressive disease (PD; RECIST 1.0). Patients with SD receiving LAN and any patient receiving PBO could enter a single-arm (LAN) OLE (NCT00842348). Main efficacy endpoint: PFS (time from core-study randomization to death/PD) for core-study intent-to-treat population from Kaplan–Meier survival analysis. Here, PFS was analyzed in subgroups of LAN–LAN patients. Results: OLE final population comprised 89 patients (LAN–LAN 42 [41 with SD]; PBO–LAN 47 [15 with SD]); 38% had pancreatic and 38% midgut NETs. During the OLE, 40% continuing LAN vs 47% switched to LAN had treatment-related adverse events. No new safety concerns were identified. Overall LAN median PFS from the LAN–LAN group was 38.5 months, and varied with tumor origin and prior therapy (Table). Conclusions: CLARINET OLE suggests sustained antitumor effects with LAN 120 mg in enteropancreatic NETs irrespective of tumor origin, and suggests benefits with LAN as early treatment. Clinical trial information: NCT00842348. [Table: see text]

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434 Background: In the CLARINET study, significant improvement in progression-free survival (primary endpoint) was reported in patients (pts) treated with lanreotide depot (LAN), a long-acting somatostatin analog, for moderately- or well-differentiated, nonfunctioning, locally advanced or metastatic GEP-NETs. A favorable safety profile was also observed. This retrospective analysis presents tumor response from CLARINET. Methods: Pts were randomized to LAN 120 mg (n=101) or PBO (n=103) once every 28 days for 96 weeks. Tumor response was evaluated centrally using RECIST version 1.0. Pts’ tumors were measured by sum of the longest diameter (SLD) of target lesions (TLs). Change was calculated for each pt’s SLD from baseline to last available post-baseline assessment. Tumor response was classified as complete response (CR): disappearance of all TLs and non-target lesions (NTLs) and no new lesions; partial response (PR): ≥30% decrease in SDL and no progressive disease (PD); stable disease (SD): not meeting criteria for CR/PR or PD; PD: ≥20% increase in SLD from baseline or nadir, unequivocal progression of NTLs or appearance of new lesions. The remaining pts were not evaluable (NE) for response. Results: 101 pts treated with LAN and 103 pts treated with PBO were assessed for tumor response. Among pts receiving LAN, 64% (65/101) demonstrated SD compared to 43% (44/103) of pts receiving PBO (Table). An additional 2 pts in the LAN group achieved a PR. Similar trends were observed in pts with pancreas and midgut origin tumors. Conclusions: A clinical benefit (defined as CR+PR+SD) of 66% (67/101) was observed with single agent LAN vs 43% (44/103) with PBO in the CLARINET population, further supporting the clinical efficacy of LAN. Clinical trial information: NCT00353496. [Table: see text]

Background/Aims: To evaluate the efficacy and safety of a triptorelin pamoate (11.25 mg) 3-month formulation in the management of central precocious puberty (CPP) (TP Study) and to retrospectively compare it with a triptorelin acetate (11.25 mg) 3-month formulation (TA Study). Methods: We conducted two phase III, multicentre, single-stage, non-comparative, open-label studies. In the TP Study, patients with CPP received an intramuscular injection of triptorelin pamoate 11.25 mg at baseline and 3 months after baseline. Hormonal changes as well as safety and efficacy endpoints were measured at baseline, 3 months, and 6 months. Results: The baseline characteristics of the 37 patients in the TP Study were similar to those of the TA Study population. A suppressed luteinising hormone (LH) response (LH peak ≤3 IU/l) to the gonadotrophin-releasing hormone test at 3 months (primary endpoint) occurred in 83.8 and 82.8% of the cases in the TP and the TA Study, respectively. At 6 months, a suppressed LH response occurred in 86.5 and 96.8% of the cases in the TP and the TA Study, respectively. Pubertal development was slowed in both studies. Adverse events were mild to moderate and resolved without sequelae in the TP Study. Conclusion: Triptorelin pamoate 11.25 mg administered at 3-month intervals is an effective and well-tolerated treatment in patients with CPP. The efficacy and safety profiles appear similar to those reported in the literature for triptorelin acetate 11.25 mg.

Background. Urinary 5-hydroxyindoleacetic acid (5-HIAA) is an established biomarker in neuroendocrine tumors and carcinoid syndrome; however, its role in nonfunctional neuroendocrine tumors is not defined. We present post hoc data on urinary 5-HIAA and plasma chromogranin A (CgA) from the CLARINET study. Methods. Patients with well-or moderately differentiated, nonfunctioning, locally advanced or metastatic enteropancreatic neuroendocrine tumors were randomized to deep subcutaneous lanreotide depot/autogel 120 mg or placebo once every 28 days for 96 weeks. Tumor response, evaluated centrally (RECIST 1.0), and progression-free survival (PFS) were assessed by treatment and biochemical response, defined as (a) baseline >upper limit of normal (ULN, 41.6 μmol per day 5-HIAA; 98.1 μg/L CgA) and (b) ≥50% decrease from baseline and to ≤ULN value on study. Results. Forty-eight percent (82 of 171; lanreotide, n = 45; placebo, n = 37) and 66% (129 of 195; lanreotide, n = 65; placebo, n = 64) of randomized patients had 5-HIAA and CgA > ULN at baseline. Among patients with >ULN baseline values who did not progress after 96 weeks of treatment,

This study prospectively collected daily patient-reported data on diarrhea and flushing from the ELECT trial to evaluate the direct impact of lanreotide depot on patients' relief of carcinoid syndrome symptoms. Treatment with lanreotide depot was associated with significant reductions in the percentages of days patients reported symptoms of diarrhea and flushing, as well as reductions in the frequency and severity of daily symptoms compared with placebo during 16 weeks of double-blind treatment. These improvements were sustained for 32 additional weeks of open-label lanreotide treatment (i.e., through week 48 of treatment), resulting in clinically meaningful, long-term symptom reduction.

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