Results of the CLARINET FORTE trial showed that lanreotide autogel (LAN) 120 mg at escalating dosing frequency (every 14 days) was associated with promising progression-free survival (PFS) benefit and no new safety issues in patients with progressive pancreatic or midgut neuroendocrine tumors (NETs).
CLARINET FORTE is a prospective, single-arm, open-label, exploratory, international phase 2 study that assessed the efficacy and safety of escalating lanreotide autogel (LAN) dose frequency (every 14 days instead of the approved every 28 days) in patients with a progressive pancreatic (pan) or midgut NET; study results were reported at the European Society for Medical Oncology Virtual Congress 2020.
Eligibility criteria included patients with a metastatic or locally advanced, unresectable, grade 1 or 2 panNET or midgut NET, with somatostatin receptor type 2 expression–positive, centrally assessed progression within the past 2 years while receiving a standard LAN regimen (120 mg every 28 days) for ≥24 weeks, with or without hormonal-related syndromes, and Ki67 ≤20%. Eligible patients received LAN 120 mg every 14 days for 48 (panNET cohort) or 96 (midgut NET cohort) weeks or until centrally assessed progressive disease (PD), unacceptable toxicity/intolerability, or death, or longer if <25 events (PD or death) had occurred. The primary end point was centrally assessed median PFS by independent central review; secondary end points included disease control rate (DCR), best overall response, and safety. The planned recruitment was 50 patients per cohort.
A total of 48 patients were enrolled in the panNET cohort and 51 patients in the midgut NET cohort. The median PFS was 5.6 months (95% confidence interval [CI], 5.5-8.3 months) and 8.3 months (95% CI, 5.6-11.1 months), respectively, in the panNET and midgut NET cohorts. Post-hoc subgroup analysis by Ki67 status showed better PFS outcomes in the panNET cohort in patients with Ki67 ≤10% (N = 43; 8.0 months [95% CI, 5.6-8.3]) compared with those with Ki67 >10% (N = 5; 2.8 months [95% CI, 2.8-2.9]); in the midgut cohort, the median PFS was 8.6 months (95% CI, 5.6-13.8) and 5.5 months (95% CI, 2.6-not calculable), respectively. At week 24, DCR was 43.8% (95% CI, 29.5-58.8) in the panNET cohort and 58.8% (95% CI, 44.2-72.4) in the midgut NET cohort; at week 48, DCR rates were 22.9% (95% CI, 12.0-37.3) and 33.3% (95% CI, 20.8-47.9), respectively.
Treatment-related adverse events (TRAEs) occurred in 37.5% of patients in the panNET cohort and 51.0% of patients in the midgut NET cohort. The majority of TRAEs were of grade 1/2 severity; only 1 grade 3 TRAE (fatigue; panNET cohort) was reported. The safety profile was found to be consistent with that previously reported for the approved dose and schedule of LAN; the most common (≤10%) classes of TRAEs were gastrointestinal disorders, occurring in 25% of patients in the panNET cohort and 37.3% of patients in the midgut NET cohort; general disorders/administration-site conditions were reported in 13.7% of patients in the midgut NET cohort. Other notable TRAEs included hyperglycemia (1 event each in the 2 cohorts), and 1 event each in the midgut NET cohort of bile stones and steatorrhea.
These results indicate that LAN 120 mg at an increasing dosing frequency of every 14 days was associated with promising efficacy outcomes, with no new safety concerns in patients with panNETs or midgut NETs. Based on these results, the authors concluded that escalating LAN dosing frequency may be a viable management strategy that could be considered before switching to an alternative treatment.
Source: Pavel ME, et al. Ann Oncol. 2020;31(suppl 4). Abstract 1162MO.