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Updated results from a phase III trial of sunitinib versus placebo in patients with progressive, unresectable, well-differentiated pancreatic neuroendocrine tumor (NET).

2012· article· en· W2601720937 on OpenAlexaff
Aaron I. Vinik, Eric Van Cutsem, Patricia Niccoli, Jean‐Luc Raoul, Yung‐Jue Bang, Ivan Borbath, Juan W. Valle, Peter Metrakos, Denis Smith, Jen‐Shi Chen, Dieter Hoersch, Daniel Castellano, Hagen F. Kennecke, Joel Picus, Guy van Hazel, Shem Patyna, Dongrui R. Lu, Richard C. Chao, Éric Raymond

Bibliographic record

VenueJournal of Clinical Oncology · 2012
Typearticle
Languageen
FieldMedicine
TopicNeuroendocrine Tumor Research Advances
Canadian institutionsBC Cancer AgencyMcGill University Health Centre
Fundersnot available
KeywordsMedicineClinical endpointSunitinibInternal medicinePlaceboNeuroendocrine tumorsProgression-free survivalRandomized controlled trialDosingGastroenterologyOverall survivalUrologyOncologySurgeryCancerPathology

Abstract

fetched live from OpenAlex

4118 Background: In a double-blind phase III trial, sunitinib (Sutent; SU) improved progression-free survival (PFS) vs placebo (PBO; 11.4 vs 5.5 mos; HR: 0.42, 95% CI: 0.26–0.66; P=0.0001) and was well tolerated in patients (pts) with unresectable, well-differentiated pancreatic NET that had progressed ≤12 mos before baseline. Initial overall survival (OS) revealed a benefit for SU vs PBO, although median OS had not been reached. We now report PFS assessed by blinded independent central review (BICR) and updated OS. Methods: Pts were randomized 1:1 to SU 37.5 mg or PBO on a continuous daily dosing schedule, each with best supportive care. The primary endpoint was investigator-assessed PFS; OS was a secondary endpoint to be evaluated every 2 yrs for 5 yrs, or until 95% of pts had died. Additionally, BICR was performed retrospectively; baseline and on-study CT/MRI scans were evaluated by a 2-reader, 2-time-point lock, followed by a sequential locked-read, batch-mode paradigm by blinded, third-party radiologists. Results: 171 pts were randomized (SU, n=86; PBO, n=85) from Jun 2007 to Apr 2009. The trial ended when an independent data monitoring committee noted efficacy favoring SU and more serious AEs and deaths with PBO. The study was unblinded at closure; pts were offered open-label SU and followed for survival. Median PFS by BICR was 12.6 mos (SU) vs 5.8 mos (PBO) (HR: 0.32, 95% CI: 0.18–0.55; P=0.00001). At study closure, there were 9 and 21 deaths in the SU and PBO arms (HR: 0.41, 95% CI: 0.19–0.89; P=0.02). By Apr 2011 (2 yrs additional follow-up) a total of 87 deaths occurred (51%), median OS was estimated at 33.0 mos in the SU arm, and 26.7 mos in the PBO arm (HR: 0.71, 95% CI: 0.47–1.09; P=0.11 [Table]). 69% of pts crossed over to SU on progression. Conclusions: BICR confirmed investigator assessment of PFS and demonstrated a 6.8-mo improvement in median PFS with SU. Updated OS favors SU, although this result is non-significant for reasons that may include crossover of treatment and limited statistical power. [Table: see text]

Fetched live from OpenAlex and de-inverted. Abstracts are not stored in this database: the inverted indexes are 8.6 GB of the frame’s 9.3 GB of text, and the host has 13 GB free.

How this classification was reachedexpand

Full frame distilled prediction

Teacher imitation

Not calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.

metaresearch head score (Codex)0.001
metaresearch head score (Gemma)0.014
Version: codex-gemma-dda1882f352aValidation status: machine_predicted_unvalidated
Candidate categoriesMetaresearch
Consensus categoriesnone
DomainCandidate signal: none · Consensus signal: none
Study designCandidate signal: Randomized trial · Consensus signal: Randomized trial
GenreCandidate signal: Empirical · Consensus signal: Empirical
Teacher disagreement score0.116
Threshold uncertainty score0.994

Codex and Gemma teacher scores by category

CategoryCodexGemma
Metaresearch0.0010.014
Meta-epidemiology (narrow)0.0000.000
Meta-epidemiology (broad)0.0030.000
Bibliometrics0.0000.001
Science and technology studies0.0000.000
Scholarly communication0.0000.000
Open science0.0000.000
Research integrity0.0000.002
Insufficient payload (model declined to judge)0.0000.000

Machine scores (provisional)

The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.

Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.

Opus teacher head0.085
GPT teacher head0.450
Teacher spread0.364 · how far apart the two teachers sit on this one work
Validation statusscore_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from it

Classification

machine, unvalidated

Machine predicted; a candidate call from one teacher head, not a consensus.

Study designRandomized trial
Domainnot available
GenreEmpirical

How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".

Quick stats

Citations16
Published2012
Admission routes1
Has abstractyes

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