For patients with progressive pancreatic or midgut neuroendocrine tumors, improvements in disease-free survival and progression-free survival were seen when the dosing of lanreotide Autogel was increased from 120 mg every 28 days to every 14 days. Data from the phase 2 CLARINET FORTE study suggest that this treatment option can delay switching to a more toxic treatment, which was presented at the 2020 ESMO Virtual Congress.
For patients with progressive pancreatic or midgut neuroendocrine tumors (NETs), improvements in disease-free survival (DFS) and progression-free survival (PFS) were seen when the dosing of lanreotide Autogel was increased from 120 mg every 28 days to every 14 days. Data from the phase 2 CLARINET FORTE study (NCT02651987) suggest that this treatment option can delay switching to a more toxic treatment, which was presented at the 2020 ESMO Virtual Congress.
The prospective open-label study assessed the efficacy and safety of lanreotide Autogel in a cohort of patients with pancreatic NETs (pan-NET; n = 48) and in a cohort of patients with midgut NETs (n = 51).
In the presentation, lead investigator Marianne Pavel, MD, chair of the Division of Endocrinology, Friedrich-Alexander-University of Erlangen-Nürnberg, Germany, reported that in patients with midgut NETs, median PFS was 8.3 months (95% CI, 5.6-11.1). For the pan-NET cohort, median PFS was 5.6 months (95% CI, 5.5-6.3).
In the pan-NET cohort, stable disease was 66.7% (95% CI, 51.6%-79.6%) and midgut NET was 68.5% (95% CI, 54.1%-80.9%). DCR at 24 weeks was reported as 43.8% (95%CI, 29.5%-58.8%) for pan-NET and 58.8% (95% CI, 44.2%-72.4%) for the midgut NET cohort.
At 48 weeks, DCR was 22.9% (95% CI, 12.0%-37.3%) for the pan-NET group and 33.3% (95% CI, 20.8%-47.9%) for the midgut NET group.
When analyzing PFS using the Ki67 test, Pavel noted that for Ki67 ≤10%, PFS for the pan-NET cohort was 8.0% (95% CI, 5.6%-8.3%) and PFS for the midgut NET was 8.6% (95% CI, 5.6%-13.8%). When Ki67 ˃10%, PFS in the pan-NET cohort was 2.8% (95% CI, 2.9-2.9%) and in the midgut NET, it was 5.5% (95% CI, 2.6-not calculable).
Patients were eligible to enroll if they had metastatic or locally advanced unresectable midgut or pancreatic NET with Ki67 ≤20%, somatostatin receptor 2+ (SSTR2+), and centrally assessed progression (as per RECIST 1.0) within the last 2 years while on a standard lanreotide regimen (120 mg every 28 days) for ≥24 weeks.
After a screening period, each cohort received 120 mg every 14 days. Patients in the pan-NET cohort were followed for 48 weeks, whereas the patients with midgut NET were followed for 96 weeks.
“Since the tumor biology between midgut and pancreatic tumors is different, the observation period is different between the 2 cohorts," Pavel said.
The primary end point was assessed median PFS by independent central review and secondary end points were disease control rate (DCR), best overall response, and safety.
The majority of baseline characteristics were similar between the 2 cohorts. Median age in the midgut NET cohort was 67.1 years and 63.3 years in the pan-NET cohort.
“The notable exception is that in the midgut NET cohort, more patients had grade 1 tumors [56.9%] than the pan-NET cohort [25.0%], whereas grade 2 tumors were higher in the pan-NET cohort versus the midgut NET cohort [75% vs 43.1%],” Pavel said. “Most of these patients had liver tumor involvement and the vast majority had less than 25% liver tumor burden.”
Regarding tolerability, most treatment-related adverse effects (TRAEs) were grade 1 for both cohorts. Most frequent side effects (≥10%) were gastrointestinal disorders reported at 25.0% in the pan-NET group and 27.3% in the midgut NET group. Administrative site reactions were reported in 13.7% of the midgut NET cohort.
“There are some side effects that are of particular interest,” Pavel said. One case of hyperglycemia was reported in each cohort, 1 case of bile duct stones was reported in the midgut NET, and 1 case of steatorrhea occurred in the midgut NET cohort.
“At the increased dosing frequency of 14 days, lanreotide Autogel provided encouraging PFS and DCR results in patients with progressive pan-NETs,” Pavel said. “Additionally, there were no new safety concerns with the increasing dosing of lanreotide.” The safety profile has been consistent with previous studies in which lanreotide has been used every 3 or 4 weeks.
Pavel M, Ċwikla JB, Lombard-Bohas C, et al. Efficacy and safety of lanreotide autogel 120 mg every 14 days in progressive pancreatic or midgut neuroendocrine tumours: CLARINET FORTE study results. Presented at: 2020 ESMO Virtual Congress. September 19-21, 2020. Abstract 1161MO.