Evaluation of the efficacy and safety of lanreotide in combination with targeted therapies in patients with neuroendocrine tumours in clinical practice: a retrospective cross-sectional analysis

Abstract

BackgroundBased on the mechanism of action, combining somatostatin analogues (SSAs) with mTOR inhibitors or antiangiogenic agents may provide synergistic effects for the treatment of patients with neuroendocrine tumours (NETs). Herein, we investigate the use of these treatment combinations in clinical practice.MethodsThis retrospective cross-sectional analysis of patients with NETs treated with the SSA lanreotide and targeted therapies at 35 Spanish hospitals evaluated the efficacy and safety of lanreotide treatment combinations in clinical practice. The data of 159 treatment combinations with lanreotide in 133 patients was retrospectively collected.ResultsOf the 133 patients, with a median age of 59.4 (16–83) years, 70 (52.6 %) patients were male, 64 (48.1 %) had pancreatic NET, 23 (17.3 %) had ECOG PS ≥2, 41 (30.8 %) had functioning tumours, 63 (47.7 %) underwent surgery of the primary tumour, 45 (33.8 %) had received prior chemotherapy, and 115 (86.5 %) had received prior SSAs. 115 patients received 1 lanreotide treatment combination and 18 patients received between 2 and 5 combinations. Lanreotide was mainly administered in combination with everolimus (73 combinations) or sunitinib (61 combinations). The probability of being progression-free was 78.5 % (6 months), 68.6 % (12 months) and 57.0 % (18 months) for patients who only received everolimus plus lanreotide (n = 57) and 89.3 % (6 months), 73.0 % (12 months), and 67.4 % (18 months) for patients who only received sunitinib and lanreotide (n = 50). In patients who only received everolimus plus lanreotide the median time-to-progression from the initiation of lanreotide combination treatment was 25.8 months (95 % CI, 11.3, 40.3) and it had not yet been reached among the subgroup of patients only receiving sunitinib plus lanreotide. The safety profile of the combination treatment was comparable to that of the targeted agent alone.ConclusionsThe combination of lanreotide and targeted therapies, mainly everolimus and sunitinib, is widely used in clinical practice without unexpected toxicities and suggests efficacy that should be explored in randomized prospective clinical trials.

Everolimus as first line therapy for pancreatic neuroendocrine tumours: current knowledge and future perspectives

“…This disease-stabilizing activity was confirmed in the randomized phase 3 clinical trial RADIANT-3 (Yao et al 2011), which documented a significantly longer PFS in patients with pNETs randomized to the association of everolimus and octreotide (11 vs. 4.6 months in the octreotide alone arm). In addition, the combination of everolimus with lanreotide suggested efficacy in a retrospective cross-sectional analysis, without unexpected toxicities, apparently through a synergistic effect (Capdevila et al 2015). The possibility of enhanced efficacy with SSAs combined with everolimus is actually being explored in randomized clinical trials, such as the phase 2 study COOPERATE-2 and the LUNA clinical trial, whose definitive results are eagerly awaited, even if preliminary data are disappointing.…”

“…Overall, 8 retrospective studies were identified (Bernard et al 2013;Capdevila et al 2015;Ferrer-Garcia et al 2013;Fiebrich et al 2011;Kulke et al 2009;Liu et al 2016;Panzuto et al 2014;Tippeswamy et al 2015), which included a total of 183 patients with pancreatic and 135 patients with extra-pancreatic NETs (see Table 2a). …”

Systemic Therapy in Incurable Gastroenteropancreatic Neuroendocrine Tumours: A Clinical Practice Guideline

“…The search uncovered eleven relevant randomized prospective studies [9][10][11][12][13][14][15][16][17][18][19] , sixteen nonrandomized prospective studies [20][21][22][23][24][25][26][27][28][29][30][31][32][33][34][35] , and thirteen retrospective studies [36][37][38][39][40][41][42][43][44][45][46][47][48] . Where multiple reports and abstracts were published for a single trial or study, only the most recent full publication was included, unless other reports contained data that were not available in the most recent publication.…”

“…Several trials included both pnets and non-pnets in their populations w ithout presenting results by subgroup 9,16,19,20,23,25,[35][36][37]39,40,43,44,46 . Because of heterogeneity and a potential for bias, those trials were not used for making the initial recommendations (pnets and non-pnets both respond differently to treatment, making it difficult to draw any conclusions from those trials).…”

GEP–NETs UPDATE: Biotherapy for neuroendocrine tumours

“…Sixty-eight (40%) patients received SSAs in combination with sunitinib and the benefit of the TKI was identified in both groups of treatment. In addition, retrospective results from a Spanish cohort treated with sunitinib (nZ61) or everolimus (nZ73) combined with lanreotide autogel showed interesting results in estimated PFS at 6 and 12 months (79.5 vs 89.3% and 68.6 vs 73% respectively) (48). Pazopanib has also been studied in the phase II trial that firstly introduced the concept of sequential therapy with targeted agents in NETs.…”