Design of an ongoing randomized study on the long-term safety and efficacy of darbepoetin alfa (DA) administered 500 mcg every three weeks (Q3W) to non-small cell lung cancer (NSCLC) patients (pts) with anemia concomitant with chemotherapy (ACC).

Abstract

TPS325 Background: Erythropoiesis-stimulating agents (ESAs) such as DA are approved for treating ACC based on controlled studies showing ESAs can raise hemoglobin (Hb) and reduce transfusions. In several controlled ACC studies in pts with small cell lung cancer or NSCLC (JCO. 2008;26:2342-49; JNCI. 2002;94:1211-20), ESAs had a neutral impact on mortality and disease progression. However, ESAs were reported to increase mortality and/or progression in some other tumor types examined in studies with high Hb targets and in one NSCLC study of pts not receiving chemotherapy or radiotherapy (JCO. 2007;25:1027-32). Since lung cancer pts often develop ACC, further studies on ESA use in these pts are warranted. We describe here a randomized trial (Amgen 20070782; ClinicalTrials.gov NCT00858364) currently enrolling to study the long-term safety of DA in NSCLC pts with ACC. Methods: Up to 500 clinical sites in ∼34 countries are targeted for this study. Pts (∼ 3000) will be randomized 2:1 to DA (500 mcg) or placebo Q3W until progression or end of chemotherapy. Key eligibility criteria include ≥ 18 years, advanced NSCLC, first-line chemotherapy, ECOG status ≤ 1, and screening Hb ≤ 11 g/dL. At Hb > 12 g/dL, study drug administration will be withheld until Hb is ≤ 12 g/dL. Noninferiority of ESA to placebo for overall survival (primary endpoint) and progression-free survival (modified RECIST per investigator; secondary endpoint) will be examined when 2700 deaths occur. Other safety endpoints include tumor response and thromboembolic events. Transfusion rates are a key efficacy endpoint; Hb changes will also be reported. This global study will likely take a year to obtain protocol approvals from all countries and to initiate study procedures at all clinical sites; 5 countries have screened pts as of December 2009. This trial aims to provide comprehensive data on whether DA affects survival, disease progression, and reduces transfusions in NSCLC pts with ACC. A better understanding of the DA benefit:risk profile in ACC may provide further global guidance for ESA use in medical practice. Author Disclosure Employment or Leadership Position Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Amgen Amgen Amgen Amgen Amgen