Quality of Life Maintained After Dose Doubling of Lanreotide Autogel in NETs

Treatment with lanreotide autogel in patients with pancreatic neuroendocrine tumors (panNETs), and midgut neuroendocrine tumors (NETs) did not cause deterioration in quality-of-life (QoL), according to new data from the Phase II CLARINET FORTE study (NCT02651987) reported in a press release from Ipsen and presented during the 18th Annual European Neuroendocrine Tumor Society Conference.^1,2

Lanreotide is a long-acting somatostatin analogue that prevents growth hormone secretion and certain hormones secreted by the digestive system.

The prospective, single-arm, open-label, European phase 2 study measured quality of life with three validated questionnaires on the severity of problems associated with mobility, selfcare, unusual activates, pain or discomfort, and anxiety or depression. Patients with metastatic or locally advanced unresectable pancreatic NETs or midgut NETs, with centrally accessed progression received 120 mg lanreotide autogel every 14 days following progression within the past 2 years on the standard dose regimen of 120 mg every 28 days. Treatment was continued until disease progression, death, or unacceptable toxicity.²

Results ultimately showed no decrease in QoL from baseline to the post-treatment period. The mean change from baseline according to the EQ-5D-5L index was –0.04 (–0.09; 0.01) and 0.00 in the panNET and midgut NET cohorts, respectively. For diarrhea, the change was 1.52 (–9.16; 12.19) for the panNET group and – 4.00 (–14.75; 6.75) for the midgut NET group. Global health status saw an improvement of –0.38 (–7.17; 6.41) in the panNET cohort and –1.33 (–8.40; 5.74) in the midgut NET cohort. For endocrine symptoms, the was a –0.53 (–5.71; 4.65) change in the panNET group and –5.09 (– 12.41; 2.23) in the midgut NET cohort. Finally, there was a –3.49 (–9.97; 2.99) change in gastrointestinal symptoms in the panNET cohort and a –2.78 (–9.52; 3.96) change in the midgut NET cohort.

Utilization of the injectable somatostatin analog also had a significant impact on cost and hospital visit reductions.

"The new findings from the CLARINET FORTE trial highlighted that QoL remained stable throughout the study in patients who were enrolled with progressive disease and who were receiving twice the frequency of injections compared with their pre-study regimen,” said Professor Marianne Pavel, Friedrich-Alexander University of Erlangen, Germany, senior physician and chair of Endocrinology, and principal investigator of the study, in a press release. "This is an important new measure as it reflects the patients’ perceptions of their own current overall health and means that patients with progressive NETs may be able to remain on a more tolerable first-line standard of care for longer with no new safety signals or quality of life deterioration."

Initial data on safety and efficacy were presented at the 2020 European Society for Medical Oncology (ESMO) Congress. The safety results showed that 37.5% of the panNET and 51.0% of the midgut NET cohorts experienced treatment-related adverse events (TRAEs). Only 1 patient in the panNET group experienced a grade 3 event of fatigue. The most common TRAEs fell into 2 classes of events. First, in the panNET and the midgut NET cohorts respectively gastrointestinal disorders (25.0% and 37.3%) were observed. Also, in the midgut NET cohort, 13.7% of patients had TRAEs classified as general disorders/administration-site conditions. The TRAEs of note in the study were hyperglycemia in 2 patients, bile stones in 1 patient, and steatorrhea in 1 patient.³

Lanreotide is licensed to treat individuals with acromegaly when levels of circulating growth hormone or insulin-like growth factor-1 remain abnormal after surgery and/or radiotherapy or in patients who otherwise require medical treatment. It is also meant to treat grade 1 and a subset of grade 2 gastroenteropancreatic neuroendocrine tumors, and symptoms associated with neuroendocrine tumors.

^REFERENCE:

1. ^{Ipsen Announces New Data from the Phase II CLARINET FORTE study which demonstrated preservation of quality of life when ncreasing dose frequencies of Somatuline® Autogel® (lanreotide). News Release. Ipsen. February 22, 2021; Accessed March 1, 2021. https://bit.ly/3bRlI4f}

2. ^{Pavel M, Ćwikła J BB , Lombard-Bohas C, et al. Efficacy, safety and quality of life (QoL) with Lanreotide Autogel (LAN) 120 mg every 14 days in progressive pancreatic or midgut neuroendocrine tumors (NETs): CLARINET FORTE study results. Presented at: 18th Annual European Neuroendocrine Tumor Society Conference; February 24-27, 2021. Virtual. Abstract H 14.}

3. ^{Pavel ME, Ćwikła J BB, Borbath I, et al. 1162MO - Efficacy and safety of lanreotide autogel (LAN) 120 mg every 14 days in progressive pancreatic or midgut neuroendocrine tumours (NETs): CLARINET FORTE study results. Ann Oncol. 2020 31 (suppl_4): S711-S724. Doi: 10.1016/annonc/annonc281}