Amgen has presented the results from a randomized, double-blind, placebo-controlled phase III study evaluating the efficacy and safety of Aranesp (darbepoetin alfa) in previously untreated patients with extensive-stage small-cell lung cancer (SCLC) receiving chemotherapy ("the 145 study") at the 2007 World Conference on Lung Cancer in Seoul, Korea.

The study demonstrated no statistically significant difference in risk of death (overall survival Aranesp compared to placebo Hazard Ratio (HR): 0.93, 95 percent CI: 0.78 to 1.11) or investigator assessed progression-free survival (HR: 1.02, 95 percent CI: 0.86, 1.21).

This study is a component of Amgen's ongoing pharmacovigilance programme designed to evaluate the effect of Aranesp on long-term survival in anaemic patients undergoing concomitant chemotherapy. The study was completed three months ahead of Amgen's post-marketing commitment, and the results were publicly announced and primary data were provided to the US Food and Drug Administration (FDA) in April 2007. Additionally, Amgen presented the results at the FDA's Oncologic Drug Advisory Committee meeting in May 2007.

As reported in April, the "145 study" demonstrated that Aranesp maintained haemoglobin (Hb) levels at a higher level than placebo and significantly reduced red blood cell (RBC) transfusions relative to placebo. The estimated difference in Hb change between the two groups was 0.84 g/dL. A total of 52 Aranesp patients (17 per cent) had at least one red blood cell transfusion during the study treatment compared to 116 patients (39 per cent) in the placebo group.

Overall, 493 of 596 patients died during the treatment period or long-term follow up through a pre-specified cut off date. In the Aranesp group, 242 patients (81 per cent) died and 251 patients (84 percent) died in the placebo group. Median survival time to death was 40 weeks for both groups.

"These study results show no statistically significant difference in overall survival or investigator assessed progression-free survival when Aranesp is used in patients with extensive-stage small-cell lung cancer receiving chemotherapy," said Robert Pirker, MD, Medical University of Vienna, Vienna, Austria. "This study is particularly important as it was conducted in a homogeneous population, receiving platinum-containing chemotherapy and the treatment arm received higher than usual doses of erythropoiesis stimulating agents (ESAs). It's important to note that this tumour type was one of the first to be reported as expressing a putative EPO receptor although subsequent rigorous studies have invalidated methodologies employed and there is at this time no conclusive evidence to indicate that the EPO receptor is in any way involved in the malignant process."

The adverse event rate was similar between the two groups. A total of 138 Aranesp patients (46 per cent) and 121 patients in the placebo group (41 percent) experienced a serious adverse event. Cardiovascular and thromboembolic events occurred at a moderately higher rate in the Aranesp group (22 per cent) than in the placebo group (15 per cent), primarily due to embolisms/thromboses (9 per cent Aranesp versus 5 per cent placebo).