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Ann Oncol. 2017 Feb 1;28(2):339-343. doi: 10.1093/annonc/mdw561.

Sunitinib in pancreatic neuroendocrine tumors: updated progression-free survival and final overall survival from a phase III randomized study.

Author information

1
Medical Oncology and Gastroenterology Department, Service Inter-Hospitalier de Cancérologie, Hôpital Beaujon and Paris Diderot University, Clichy.
2
Cancer Care, Institut Paoli-Calmettes, and RENATEN Network, Marseille, France.
3
Department of Medical Oncology, Hospital Universitario 12 de Octubre, Madrid, Spain.
4
Medical Oncology Department, The University of Manchester/The Christie NHS Foundation Trust, Manchester, UK.
5
Translational Medicine - Digestive Cancers, Institut Paoli-Calmettes and RENATEN Network, Marseille, France.
6
Eastern Virginia Medical School Streilitz Diabetes Research Center and Neuroendocrine Unit, Norfolk, USA.
7
Digestive Oncology Unit, University Hospitals Leuven and KU Leuven, Leuven, Belgium.
8
Seoul National University College of Medicine, Seoul National University Hospital, Seoul, Republic of Korea.
9
Hepato-Gastroenterology Unit, Cliniques Universitaires Saint-Luc, Brussels, Belgium.
10
Medical Oncology Department, Hôpital Edouard Herriot, Hospices Civils de Lyon, Lyon, France.
11
McGill University Hospital Centre, Montreal, Canada.
12
Oncology Department, University Hospital, Bordeaux, France.
13
Linkou Chang Gung Memorial Hospital and Chang Gung University, Tao-Yuan, Taiwan.
14
Centre Hospitalier Universitaire Timone, Assistance Publique-Hôpitaux de Marseille, Aix-Marseille Université, and RENATEN Network, Marseille, France.
15
Pfizer Oncology, La Jolla, USA.
16
Department of Evidera, St-Laurent, Canada.

Abstract

Background:

In a phase III trial in patients with advanced, well-differentiated, progressive pancreatic neuroendocrine tumors, sunitinib 37.5 mg/day improved investigator-assessed progression-free survival (PFS) versus placebo (11.4 versus 5.5 months; HR, 0.42; P < 0.001). Here, we present PFS using retrospective blinded independent central review (BICR) and final median overall survival (OS), including an assessment highlighting the impact of patient crossover from placebo to sunitinib.

Patients and methods:

In this randomized, double-blind, placebo-controlled study, cross-sectional imaging from patients was evaluated retrospectively by blinded third-party radiologists using a two-reader, two-time-point lock, followed by a sequential locked-read, batch-mode paradigm. OS was summarized using the Kaplan-Meier method and Cox proportional hazards model. Crossover-adjusted OS effect was derived using rank-preserving structural failure time (RPSFT) analyses.

Results:

Of 171 randomized patients (sunitinib, n = 86; placebo, n = 85), 160 (94%) had complete scan sets/time points. By BICR, median (95% confidence interval [CI]) PFS was 12.6 (11.1-20.6) months for sunitinib and 5.8 (3.8-7.2) months for placebo (HR, 0.32; 95% CI 0.18-0.55; P = 0.000015). Five years after study closure, median (95% CI) OS was 38.6 (25.6-56.4) months for sunitinib and 29.1 (16.4-36.8) months for placebo (HR, 0.73; 95% CI 0.50-1.06; P = 0.094), with 69% of placebo patients having crossed over to sunitinib. RPSFT analysis confirmed an OS benefit for sunitinib.

Conclusions:

BICR confirmed the doubling of PFS with sunitinib compared with placebo. Although the observed median OS improved by nearly 10 months, the effect estimate did not reach statistical significance, potentially due to crossover from placebo to sunitinib.

Trial registration number:

NCT00428597.

KEYWORDS:

VEGFR inhibitor; antiangiogenics; blinded independent central review; crossover; rank-preserving structural failure time (RPSFT)

PMID:
27836885
DOI:
10.1093/annonc/mdw561
[Indexed for MEDLINE]

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