CLARINET FORTE assessed the efficacy and safety of increasing LAN 120 mg dose frequency from every (q) 28 days (standard) to q14 days in patients with a progressive pancreatic NET (panNET) or midgut NET.
A prospective, single-arm, open-label, exploratory, international phase II study in patients with a metastatic or locally advanced, unresectable, G1/2 panNET or midgut NET, with centrally assessed progression within the last 2 years while on a standard LAN regimen for ≥24 weeks. Planned recruitment was 50 patients per cohort. LAN 120 mg q14 days was administered for 48 (panNET) or 96 (midgut) weeks (or until centrally-assessed progressive disease, unacceptable toxicity/tolerability, or death), or longer if <25 events had occurred.
In the panNET (N=48) and midgut NET (N=51) cohorts, respectively, median (95% confidence interval [CI]) progression-free survival (PFS, primary endpoint) was 5.6 (5.5; 8.3) and 8.3 (5.6; 11.1) months. Post-hoc subgroup analysis in the panNET cohort showed median (95% CI) PFS of 8.0 (5.6; 8.3) months in patients with Ki67 ≤10% (N=43), and 2.8 (2.8; 2.9) months in patients with Ki67 >10% (N=5). Disease control rate (DCR; proportion of patients with complete response, partial response or stable disease; 95% CI) in the panNET and midgut NET cohorts, respectively: Week 24, 43.8% (29.5; 58.8) and 58.8% (44.2; 72.4); Week 48, 22.9% (12.0; 37.3) and 33.3% (20.8; 47.9). Treatment-related adverse events (TRAEs) occurred in 37.5% and 51.0% of patients in the panNET and midgut NET cohorts, respectively; only one TRAE was G≥3 (panNET: fatigue [N=1], G3). The most common (≥10%) classes of TRAEs were gastrointestinal disorders (panNET, 25.0%; midgut NET, 37.3%) and general disorders/administration-site conditions (midgut NET, 13.7%). Of note, the following TRAEs occurred: hyperglycaemia (N=2), bile stones (N=1), steatorrhea (N=1).
LAN 120 mg q14 days in patients with panNETs or midgut NETs (progressive on standard LAN dose) produced promising PFS and DCR. In the pan-NET cohort, the outcome was more favourable in patients with Ki67 ≤10%. Safety was consistent with the known safety profile of LAN.
Clinical trial identification
Jessica Woods, BMedSci (Hons), on behalf of Watermeadow Medical, an Ashfield company, provided medical writing support, which was funded by the study sponsor in accordance with Good Publication Practice guidelines.
Legal entity responsible for the study
M.E. Pavel: Honoraria (self), Advisory/Consultancy: Ipsen; Honoraria (self), Advisory/Consultancy: Novartis; Honoraria (self), Advisory/Consultancy: Pfizer; Honoraria (self), Advisory/Consultancy: AAA; Honoraria (self), Advisory/Consultancy: Lexicon. J.B. Ćwikła: Honoraria (self): Ipsen. C. Lombard-Bohas: Advisory/Consultancy, Research grant/Funding (self): Ipsen; Advisory/Consultancy: Pfizer; Advisory/Consultancy, Research grant/Funding (self): Novartis. I. Borbath: Advisory/Consultancy: Pfizer; Advisory/Consultancy, Research grant/Funding (self): Novartis; Advisory/Consultancy, Research grant/Funding (self): Ipsen; Research grant/Funding (self): Bayer; Research grant/Funding (self): Celgene. T. Shah: Honoraria (self), Advisory/Consultancy, Travel/Accommodation/Expenses: Ipsen. U-F. Pape: Honoraria (self), Advisory/Consultancy, Speaker Bureau/Expert testimony, Research grant/Funding (self): Ipsen; Honoraria (self), Research grant/Funding (self): Novartis. X-M. Truong Thanh: Full/Part-time employment: Ipsen. A. Houchard: Full/Part-time employment: Ipsen. P. Ruszniewski: Advisory/Consultancy: Novartis; Advisory/Consultancy: Ipsen; Advisory/Consultancy: AAA; Advisory/Consultancy: ITM; Advisory/Consultancy: Keocyt.