Cabozantinib Improves Progression-Free Survival in Patients With Carcinoid and Pancreatic NETs: Presented at ENETS

By Jenny Powers

BARCELONA, Spain -- March 13, 2018 -- Cabozantinib demonstrated promising activity and improved progression-free survival (PFS) in patients with carcinoid or pancreatic neuroendocrine tumours (pNETs), according to a study presented here at the 15th Annual Conference of the European Neuroendocrine Tumor Society (ENETS).

In the study, patients with each disease type demonstrated partial response (PR) or stable disease (SD).

The objective response rate (ORR) -- the primary endpoint -- in patients with pNET was 15%, including PR in 3 (15%) patients SD in 15 (75%) patients.

Of the 41 patients with carcinoid, the ORR was 15%, with 6 (15%) patients achieving PR and 26 (63%) patients showing SD. Two (5%) patients experienced progressive disease and the response was unknown in 7 (17%) patients, where treatment was halted prior to staging.

“Treatment with cabozantinib was associated with objective tumour responses in both NET subgroups,” said Jennifer A. Chan, MD, Dana Farber Cancer Institute, Boston, Massachusetts.

The researchers enrolled patients with progressive, well differentiated, grades 1 to 2 carcinoid or pNET in parallel cohorts. The patients had received prior treatment and there was no limit on the amount or type. The study accrued 41 patients with carcinoid with an ECOG PS 0/1. Accrual to the pNET cohort was halted due to a decision made by the investigators and sponsor at 20 patients.

Patients received oral cabozantinib 60 mg/day. Restaging was done every 2 months for the first 6 months, and every 3 months thereafter. The carcinoid group completed a median of 8 (range, 0-44) 28-day treatment cycles and the pNET group completed a median of 10 (range, 0-35) cycles; 14 patients remain on treatment.

The median PFS in patients with pNETs was 21.8 months and 31.4 months for patients with carcinoid.

“The median PFS durations are encouraging in the context of historical controls,” said Dr. Chan.

Of the 53 patients completing more than 1 cycle of treatment, 81% of patients required a dose reduction.

“Although dose reduction was common, overall the treatment was tolerable and the toxicity profile is consistent with data in other disease settings,” said Dr. Chan.

Of the patients, 51% discontinued the trial due to disease progression or death, 28% of patients discontinued the study due to withdrawal of consent or investigator decision, and 21% stopped treatment due to adverse events (AEs).

Grade 3/4 toxicities occurring in ≥1 patient included hypertension (13%), hypophosphatemia (11%), diarrhoea (10%), lymphopenia (7%), thrombocytopenia (5%), fatigue (5%), and increased lipase or amylase (8%).

Other grade 3/4 AEs that were unexpected were heart failure and autoimmune hemolytic anaemia, which each occurred in 1 patient.

“A randomised phase 3 trial to further assess the activity of cabozantinib in carcinoid and pancreatic NET is already in development,” said Dr. Chan.

Funding for this study was provided by Exelixis.

[Presentation title: Phase II Trial of Cabozantinib in Patients With Carcinoid And Pancreatic Neuroendocrine Tumors (pNET). Abstract OR0091]

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