Antiproliferative effects of lanreotide autogel in patients with progressive, well-differentiated neuroendocrine tumours: a Spanish, multicentre, open-label, single arm phase II study

Marta Martín-Richard, Bartomeu Massutí, Eva Pineda, Vicente Alonso, Maribel Marmol, Daniel Castellano, Emilio Fonseca, Antonio Galán, Marta Llanos, Maria Angeles Sala, Carlos Pericay, Fernando Rivera, Javier Sastre, Angel Segura, Maria Quindós, Pascal Maisonobe, TTD (Tumores del Tracto Digestivo) Study Group, Bartomeu Massutí, Marta Martín-Richard, Vicente Alonso, Daniel Castellano, Emilio Fonseca, Antonio Galán, J Luis García López, Marta Llanos, Inmaculada Maestu, Lorena del Río Pazos, Joan Maurel, María Purificación Martínez de Prado, Carlos Pericay, Fernando Rivera, Javier Sastre, Ángel Segura, Manuel Valladares, Amalia Velasco, Marta Martín-Richard, Bartomeu Massutí, Eva Pineda, Vicente Alonso, Maribel Marmol, Daniel Castellano, Emilio Fonseca, Antonio Galán, Marta Llanos, Maria Angeles Sala, Carlos Pericay, Fernando Rivera, Javier Sastre, Angel Segura, Maria Quindós, Pascal Maisonobe, TTD (Tumores del Tracto Digestivo) Study Group, Bartomeu Massutí, Marta Martín-Richard, Vicente Alonso, Daniel Castellano, Emilio Fonseca, Antonio Galán, J Luis García López, Marta Llanos, Inmaculada Maestu, Lorena del Río Pazos, Joan Maurel, María Purificación Martínez de Prado, Carlos Pericay, Fernando Rivera, Javier Sastre, Ángel Segura, Manuel Valladares, Amalia Velasco

Abstract

Background: Somatostatin analogues (SSAs) are indicated to relieve carcinoid syndrome but seem to have antiproliferative effects on neuroendocrine tumours (NETs). This is the first prospective study investigating tumour stabilisation with the long-acting SSA lanreotide Autogel in patients with progressive NETs.

Methods: This was a multicentre, open-label, phase II trial conducted in 17 Spanish specialist centres. Patients with well-differentiated NETs and radiologically confirmed progression within the previous 6 months received lanreotide Autogel, 120 mg every 28 days over ≤92 weeks. The primary endpoint was progression-free survival (PFS). Secondary endpoints were response rate, tumour biomarkers, symptom control, quality of life (QoL), and safety. Radiographic imaging was assessed by a blinded central radiologist.

Results: Of 30 patients included in the efficacy and safety analyses, 40% had midgut tumours and 27% pancreatic tumours; 63% of tumours were functioning. Median PFS time was 12.9 (95% CI: 7.9, 16.5) months, and most patients achieved disease stabilisation (89%) or partial response (4%). No deterioration in QoL was observed. Nineteen patients (63%) experienced treatment-related adverse events, most frequently diarrhoea and asthenia; only one treatment-related adverse event (aerophagia) was severe.

Conclusion: Lanreotide Autogel provided effective tumour stabilisation and PFS >12 months in patients with progressive NETs ineligible for surgery or chemotherapy, with a safety profile consistent with the pharmacology of the class.

Trial registration: ClinicalTrials.gov Identifier NCT00326469; EU Clinical Trial Register EudraCT no 2004-002871-18.

Figures

Figure 1
Figure 1
Kaplan–Meier plot of PFS among patients treated with lanreotide autogel (n = 27).
Figure 2
Figure 2
Maximum change in sum of longest diameters of target NET lesions (n = 27). Each bar represents data for a single patient.

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