Diabetes mellitus (DM) is a risk factor for pancreatic NETs, but its prognostic role in stage IV NETs is less defined. We evaluated the impact of diabetes on PFS in patients with advanced, non-functioning GEP-NETs.
Post hoc analysis of data from the phase III double-blind, placebo-controlled CLARINET study (NCT00353496) to investigate association between DM (any of: medical history of type 1 or 2; use of antihyperglycemic medication; HbA1c ≥6.5%, fasting plasma glucose ≥7mmol/L; non-fasting plasma glucose ≥11.11mmol/L [at baseline or during study]) and PFS (Kaplan-Meier). Multivariate Cox analysis including treatment (LAN vs PBO), DM at baseline, previous therapy and progression at baseline was used to test interaction between DM and LAN efficacy.
The overall population (total, n = 204; LAN, n = 101; PBO, n = 103) had well-differentiated (Ki-67 <10%) foregut (45%), midgut (36%), or hindgut (7%) and unknown (13%) NET. 79 patients had DM, 125 did not (N-DM); 24 received metformin in combination with LAN (n = 14) or PBO (n = 10). Median PFS (mPFS) was 96.0 months (mo) [95% CI: 70.4; not reached (NR)] for DM vs 98.0 mo [72.1;NR] for N-DM (HR 1.20 [0.79;1.82], p = 0.38). For DM, mPFS with LAN (n = 42) was NR [95.9;NR] vs 60.0 mo [48.0;74.4] with PBO (n = 37) (HR 0.27, [0.13-0.57], p = 0.0002). For N-DM, mPFS with LAN (n = 59) was NR [96.0;NR] vs 72.1 mo [52.0;NA] with PBO (n = 66) (HR 0.64 [0.35-1.15], p = 0.04). In multivariate analysis, DM at baseline was not significantly associated with PFS (HR 1.64 [0.95;2.84], p = 0.08). Significant impact of LAN on PFS was confirmed (HR 0.53 [0.31;0.89], p = 0.02), without significant interaction between LAN efficacy and DM (p = 0.62).
DM did not emerge as a negative prognostic factor in advanced stage IV NETs. Efficacy of LAN in DM and N-DM was confirmed. Although LAN–DM interaction was not significant, LAN efficacy seemed particularly favorable in DM compared to N-DM patients, in terms of HR. These findings, along with a potential favorable association with hypoglycemic drugs such as metformin, should be evaluated and validated in prospective biomarker studies.
Clinical trial identification
Post hoc analisys of phase III double-blind, placebo-controlled CLARINET study (NCT00353496).
Legal entity responsible for the study
Editorial assistance for the preparation of this abstract was provided by Emma Leah, Global Publications Manager, Rare Diseases, Ipsen.
S. Pusceddu: Honoraria, advisory boards: Novartis; Research funding, honoraria, advisory boards, consulting role, grants: Ipsen; Advisory boards: Italfarmaco; Research funding, advisory boards, grants: Pfizer; Advisory boards: Advanced Accelerate Application (AAA). R. Buzzoni: Research funding, advisory boards: Ipsen. F.G.M. de Braud: Research funding, honoraria, advisory boards, consulting role, grants: Ipsen. N. Prinzi: Honoraria: Ipsen. X-M. Truong-Thanh: Employment: Ipsen. V. Mazzaferro: Honoraria: Ipsen. All other authors have declared no conflicts of interest.