Combined Lanreotide Autogel and Temozolomide Treatment of Progressive Pancreatic and Intestinal Neuroendocrine Tumors: The Phase II SONNET Study.

BACKGROUND: In advanced neuroendocrine tumors (NET), antiproliferative treatment options beyond somatostatin analogs remain limited. Temozolomide (TMZ) has shown efficacy in NET alone or combined with other drugs. MATERIALS AND METHODS: SONNET (NCT02231762) was an open, multicenter, prospective, phase II study to evaluate lanreotide autogel 120 mg (LAN) plus TMZ in patients with progressive advanced/metastatic grade 1/2 gastroenteropancreatic (GEP) NET or of unknown primary. Patients could be enrolled at first-line or higher therapy line. The primary endpoint was disease control rate ([DCR], rate of stable disease [SD], partial [PR], and complete response [CR]) at 6 months of LAN and TMZ. Patients with nonfunctioning (NF) NET without progression at 6 months were randomized to 6-month LAN maintenance or watch and wait, patients with functioning (F)-NET with clinical benefit (PR, SD) continued on LAN. RESULTS: Fifty-seven patients were recruited. The majority of patients received the study drug at second or higher treatment line and had an NET G2. DCR at 6 months LAN and TMZ was 73.5%. After 6 months of further LAN maintenance, 54.5% of patients with F-NET and 71.4% with NF-NET had SD or PR vs 41.7% with NF-NET on observation only. LAN and TMZ were effective in all subgroups analyzed. At 12 months of follow-up, median progression-free survival was 11.1 months. Median serum chromogranin A decreased except in NF-NET on observation. O6-methylguanine DNA methyltransferase promoter methylation appeared to better reflect TMZ response than loss of gene expression. During combination therapy, the most frequent treatment-emergent adverse events grade 3/4 reported were nausea (14%), thrombocytopenia (12.3%), and neutropenia (8.8%). Four deaths were reported resulting from severe adverse events not considered related to study medication. CONCLUSIONS: LAN plus TMZ is a treatment option for patients with progressive GEP-NET with more aggressive biological profile showing a manageable safety profile.

How to Implement Adherence-Promoting Programs in Clinical Practice? A Discrete Choice Experiment on Physicians' Preferences.

INTRODUCTION: The aim of this study was to examine physicians' preferences regarding adherence-promoting programs (APPs), and to investigate which APP characteristics influence the willingness of physicians to implement these in daily practice. MATERIALS AND METHODS: A discrete choice experiment was conducted among general practitioners, cardiologists, neurologists and ophthalmologists in Germany. The design considered five attributes with two or three attribute levels each: validation status of the APP; possibility for physicians to receive a certificate; type of intervention; time commitment per patient and quarter of the year to carry out the APP; reimbursement for APP participation, per included patient and quarter of the year.A multinomial logit model was run to estimate physicians' utility for each attribute and to evaluate the influence of different levels on the probability of choosing a specific APP. The relative importance of the attributes was compared between different pre-defined subgroups. RESULTS: In total, 222 physicians were included in the analysis. The most important characteristics of APPs were time commitment to carry out the program (34.8% importance), reimbursement (33.3%), and validation status of the program (23.7%). The remaining attributes (type of intervention: 3.6%; possibility to receive a certificate: 4.7%) were proven to be less important for a physician's decision to participate in an APP. Physicians on average preferred APP alternatives characterized by little time commitment (ß=1.456, p<0.001), high reimbursement for work (ß=1.392, p<0.001), "positive validation status" (ß=0.990, p<0.001), the "possibility to get a certificate" (ß=0.197, p<0.001), and the provision of "tools for both physicians and patients" (ß=0.150, p<0.001). CONCLUSION: For the majority of the physicians participating in this survey, the willingness to implement an APP is determined by the associated time commitment and reimbursement. Considering physicians' preferences regarding different APP features in the promoting process of these programs may enhance physicians' participation and engagement.