An independent review of the benefit of Pfizer’s Sutent in a Phase III trial in pancreatic neuroendocrine tumours has confirmed the original findings of the investigators that the drug results in a clinically significant improvement in progression-free survival compared with placebo.
The study was stopped early following a planned review by a data monitoring committee in February 2009, which recommended that all patients should be offered Sutent (sunitinib) because of its efficacy. However, as Juan Valle of the Christie Hospital in Manchester, explains, a new review of data was necessary because the positive results were questioned on the basis that the estimates of PFS may have been subject to bias in the original trial.
“The results were based on investigator assessments and once the trial was stopped, some commentators suggested that the results could have been biased because sunitinib can have some very particular and obvious side effects, therefore investigators may have been able to tell who was taking the active drug rather than placebo. An independent review was necessary to determine if the results stood up, irrespective of any unintentional unblinding,” added Dr Valle.
A retrospective, blinded, independent central review of imaging studies was therefore conducted in a large subset of patients from the trial and presented here at the European Society for Medical Oncology congress in Milan. Its findings support the original findings of the investigator-assessed PFS and a review for the whole population in the original trial is ongoing, to be presented later this year.
Results from the Phase III trial were first reported at ECCO/ESMO last year. Investigators had assessed the safety and efficacy of placebo or sunitinib 37.5 mg/day continuous daily dosing, with best supportive care, in patients with well-differentiated pancreatic islet cell tumors not amenable to curative therapy.
Their interim analysis showed that median progression-free survival was 11.1 months with sunitinib versus 5.5 months for placebo. The hazard ratio for progression-free survival was 0.397 in favour of sunitinib (p < 0.001), giving a 60% improvement.
Sutent is the standard of care for first-line treatment of metastatic renal cell cancer and has been shown in this tumour type to extend overall survival beyond two years. It has also been approved for the treatment of imatinib-resistant/intolerant gastrointestinal stromal tumours.
By Rhonda Siddall in Milan