1146MO - Interim analysis of CABONEN: A multicenter phase II trial investigating cabozantinib in patients with advanced, low proliferative NEN G3

Background

The prognosis of patients with neuroendocrine neoplasia (NEN) depends mainly on the proliferation index Ki67. Patients with low-grade NEN (G1, Ki67 <3%) frequently survive more than ten years, those with NET G2 (Ki67 3-20%) have a moderate prognosis while patients with a Ki67 >20% (G3) often survive less than 12 months. For patients with NET G1/G2, a variety of treatment options are available, while for NEN G3 the choice is limited. Among NEN G3, those with a Ki67 of >60% respond well to platinum-based chemotherapies, while there is no trial-proven treatment for slower proliferating G3 tumors. The CABONEN study evaluates cabozantinib, which has shown activity in NEN G1/G2, in NEN G3 with a Ki67 up to 60%.

Methods

CABONEN is a prospective, single-arm, multicenter phase II trial which investigates the efficacy and safety of cabozantinib in NEN G3 patients with a Ki67 between 20% and 60%. Primary endpoint is disease control rate (DCR) after 6 months; secondary endpoints include DCR after 3 and 12 months, progression-free survival (PFS), overall survival (OS), objective response rate (ORR), quality of life, and toxicity.

Results

From December 2021 to March 2024, 32 of 40 planned patients (16 female, 16 male) were enrolled. Of these, 26 patients had NET G3, and 6 patients had NEC Ki67low. The median age at diagnosis was 61.5 years (40 to 80). The primary tumor location was the pancreas in 46.9% (15), the GI tract in 25% (8), the lung in 9.4% (3), and others in 18.8 % (6). The median Ki67 was 31% (21% to 60%). Patients were therapeutically naïve in 31% (10), had received 1 prior therapy in 41% (13), or had received 2 or more therapeutic lines in 28.1% (9). The primary end point DCR after 6 months was 64.1% and after 3 months 80.1%. The PFS was 6.7 months. ORR after 3 months (20 patients) showed PR 10% (2), SD 75% (15), and PD 15% (3). During therapy, a total of 26 SAEs were observed including 22 SAE grade 3, 1 SAE grade 4, and 3 SAE grade 5, with SAEs including ileus, acute pain, cholangiosepsis, intestinal perforation, or stroke. A Data and Safety Monitoring Board could not find new and unexpected AEs and recommends continuation of the study.

Conclusions

Cabozantinib has shown to be a safe and effective treatment option in patients with low proliferative NEN G3.

Clinical trial identification

NCT04524208, 24.08.2020.

Editorial acknowledgement

Legal entity responsible for the study

The Sponsor of the CABONEN Trial represents the University Medical Center Göttingen.

Funding

Ipsen Pharma.

Disclosure

All authors have declared no conflicts of interest.