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

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.

The design of an observational study of hypertension management, adherence and pressure control in Blood Pressure Success Zone Program participants.

AIMS: The Blood Pressure Success Zone (BPSZ) Program, a nationwide initiative, provides education in addition to a complimentary trial of one of three antihypertensive medications. The BPSZ Longitudinal Observational Study of Success (BPSZ-BLISS) aims to evaluate blood pressure (BP) control, adherence, persistence and patient satisfaction in a representative subset of BPSZ Program participants. The BPSZ-BLISS study design is described here. METHODS: A total of 20,000 physicians were invited to participate in the study. Using a call centre supported Interactive Voice Response System (IVRS), physicians report BP and other data at enrolment and every usual care visit up to 12 +/- 2 months; subjects self-report BPs, persistence, adherence and treatment satisfaction at 3, 6 and 12 months post-BPSZ Program enrolment. In addition to BPSZ Program enrolment medications, physicians prescribe antihypertensive medications and schedule visits as per usual care. The General Electric Healthcare database will be used as an external reference. RESULTS: After 18 months, over 700 IRB approved physicians consented and enrolled 10,067 eligible subjects (48% male; mean age 56 years; 27% newly diagnosed); 97% of physicians and 78% of subjects successfully entered IVRS enrolment data. Automated IVRS validations have maintained data quality (< 5% error on key variables). Enrolment was closed 30 April 2007; study completion is scheduled for June 2008. CONCLUSIONS: The evaluation of large-scale health education programmes requires innovative methodologies and data management and quality control processes. The BPSZ-BLISS design can provide insights into the conceptualisation and planning of similar studies.

Oxybutynin extended release and tolterodine immediate release : a health economic comparison.

OBJECTIVE: To evaluate the cost-effectiveness of a new extended-release (XL) formulation of oxybutynin relative to tolterodine immediate release (IR), currently the most prescribed treatment for overactive bladder in the UK. METHODS: A state-transition model was developed to compare outcomes over 1 year. Effectiveness and treatment persistence data were derived from the OBJECT (Overactive Bladder: Judging Effective Control and Treatment) study, a 3-month clinical trial comparing oxybutynin XL 10 mg/day with tolterodine IR 4 mg/day. The daily costs of oxybutynin XL and tolterodine IR were pound0.82 and pound1.04, respectively. These data and information from the literature were used to project outcomes beyond the trial time. Severity-specific incontinence cost profiles were developed for the UK (2002 costings). RESULTS: After 1 year, 3.1 more patients per 100 treated attained complete continence with oxybutynin XL compared with tolterodine IR, and 5.6% more had less than seven incontinent episodes per week. Over 1 year, patients receiving oxybutynin XL had almost 17 additional incontinence-free days and 95 fewer incontinent episodes. Estimated costs were pound86 lower per patient with oxybutynin XL. If drugs are priced equally, savings decrease to pound21 per patient. Oxybutynin XL maintains its advantage over wide ranges of inputs, and outcomes are similar if analyses are limited to 3 months. CONCLUSION: Base-case analyses suggest that oxybutynin XL provides better effectiveness than tolterodine IR and reduces costs. Results indicate that oxybutynin XL is the dominant therapeutic option under a wide range of alternative inputs and assumptions.