Updated Efficacy and Safety Outcomes for Patients with Well-Differentiated Pancreatic Neuroendocrine Tumors Treated with Sunitinib

Abstract

Background: Sunitinib prolonged progression-free survival (PFS) versus placebo in patients with metastatic pancreatic neuroendocrine tumors (panNETs) in a phase III trial. The efficacy and safety of sunitinib in patients with panNETs were confirmed in an open-label phase IV trial.

Objective: To assess the clinical benefit with sunitinib using the combined data from these trials.

Patients and methods: An updated overall survival (OS) in patients with panNETs for the phase IV trial was provided, and an analysis of results from the sunitinib-treated combined cohort from the phase III and IV trials (combined cohort) was conducted to assess PFS, OS, and objective response rate (ORR).

Results: The updated median OS for the phase IV trial was 54.1 months (95% CI 37.9-not reached). Investigator-assessed median PFS for the combined cohort (n = 102) was 12.9 months (95% CI 7.4-16.7) with a significant benefit versus placebo in the phase III trial (n = 35) (HR 0.429; 95% CI 0.245-0.752; p = 0.001). Median OS could not be calculated for the combined cohort or placebo group due to the high number of patients censored; however, the estimated HR of 0.303 (CI 0.100-0.921; p = 0.013) favored sunitinib. ORR for the combined cohort was 16.7% (95% CI 10.0-25.3). Sunitinib was well tolerated in both trials with a safety profile similar to previously seen in other studies.

Conclusions: The combined analysis of these studies confirms the objective tumor responses and improvements in PFS observed in the initial phase III trial, providing further support for the clinical benefit of sunitinib in patients with advanced panNETs. CLINICALTRIALS.

Gov identifiers: NCT00428597 and NCT01525550.

Conflict of interest statement

Eric Raymond is a consultant for and has received grants for clinical trials from Ipsen, Novartis, Eli Lilly, and Pfizer. Matthew H. Kulke has participated on advisory boards for Ipsen and Novartis. Nicola Fazio has received honoraria from Pfizer; he has participated on advisory boards for Novartis, Pfizer, and Ipsen, Merck Serono, MSD, and AAA; and his institution has received research funds from Novartis and Merck Serono. Brad Rosbrook and Kathrine Fernandez are employees of and hold stock in Pfizer.

Figures

Fig. 1

Progression-free survival (PFS) for the combined phase III and phase IV treatment-naïve sunitinib cohort versus the treatment-naïve placebo cohort in the phase III trial. CI confidence interval

Fig. 2

Tumor swimmer plot investigator-assessed response for phase IV full analysis set. a Treatment-naïve cohort phase IV trial and b later-line cohort phase IV trial. PD progressive disease

Fig. 3

Overall survival for the combined phase III and phase IV treatment-naïve sunitinib cohort versus the treatment-naïve placebo cohort in the phase III trial. CI confidence interval

Fig. 4

Maximum percent change from baseline in the sum of the longest diameters of target lesions as assessed by the investigators. a Combined phase III and phase IV treatment-naïve cohort sunitinib arm and b treatment-naïve cohort placebo arm from the phase III trial. CR complete response, NE not evaluable, PD progressive disease, PR partial response, SD stable disease