Pere Gascón1, Rajnish Nagarkar2, Martin Šmakal3, Konstantinos N Syrigos4, Carlos H Barrios5, Jesús Cárdenas Sánchez6, Li Zhang7, David H Henry8, David Gordon9, Vera Hirsh10, Kaoru Kubota11, Sergey Orlov12, Gary Thomas13, Tilman Steinmetz14, Jin-Hyoung Kang15, Dianne K Tomita16, Alexander N Fleishman16, Joseph K Park16, Cisio De Oliveira Brandao16. 1. Department of Hematology-Oncology, Hospital Clínic de Barcelona, University of Barcelona, Barcelona, Spain. Electronic address: gascon@clinic.cat. 2. Curie Manavata Cancer Center, Nashik, India. 3. Nemocnice Hořovice, NH Hospital a.s., Hořovice, Czech Republic. 4. Third Department of Medicine, Athens Medical School, Athens, Greece. 5. Centro de Pesquisa em Oncologia, PUCRS, Porto Alegre, Brazil. 6. Centro Medico de Colima, Colima, Mexico. 7. Sun Yat-Sen University Cancer Center, East Guangzhou, China. 8. University of Pennsylvania, Philadelphia, Pennsylvania. 9. Cancer Care Centers of South Texas and US Oncology Research Network, San Antonio, Texas. 10. MUHC Royal Victoria Hospital, Montreal, Quebec, Canada. 11. Nippon Medical School, Tokyo, Japan. 12. Saint Petersburg State Medical University, Saint Petersburg, Russian Federation. 13. South Carolina Cancer Specialists, Hilton Head Island, South Carolina. 14. Gemeinschaftspraxis für Hämatologie und Onkologie, Köln, Germany. 15. The Catholic University of Korea, Seoul, South Korea. 16. Amgen Inc., Thousand Oaks, California.
Abstract
INTRODUCTION: This study evaluated noninferiority of darbepoetin alfa versus placebo for overall survival (OS) and progression-free survival (PFS) in anemic patients with NSCLC treated to a 12.0-g/dL hemoglobin (Hb) ceiling. METHODS: Adults with stage IV NSCLC expected to receive two or more cycles of myelosuppressive chemotherapy and Hb less than or equal to 11.0 g/dL were randomized 2:1 to blinded 500 μg darbepoetin alfa or placebo every 3 weeks. The primary endpoint was OS; a stratified Cox proportional hazards model was used to evaluate noninferiority (upper confidence limit for hazard ratio [HR] < 1.15). Secondary endpoints were PFS and incidence of transfusions or Hb less than or equal to 8.0 g/dL from week 5 to end of the efficacy treatment period. RESULTS: The primary analysis set included 2516 patients: 1680 were randomized to darbepoetin alfa; 836 to placebo. The study was stopped early per independent Data Monitoring Committee recommendation after the primary endpoint was met with no new safety concerns. Darbepoetin alfa was noninferior to placebo for OS (stratified HR = 0.92; 95% confidence interval [CI]: 0.83‒1.01) and PFS (stratified HR = 0.95; 95% CI: 0.87‒1.04). Darbepoetin alfa was superior to placebo for transfusion or Hb less than or equal to 8.0 g/dL from week 5 to end of the efficacy treatment period (stratified odds ratio = 0.70; 95% CI: 0.57‒0.86; p < 0.001). Objective tumor response was similar between the groups (darbepoetin alfa, 36.4%; placebo, 32.6%). Incidence of serious adverse events was 31.1% in both groups. No unexpected adverse events were observed. CONCLUSIONS: Darbepoetin alfa dosed to a 12.0-g/dL Hb ceiling was noninferior to placebo for OS and PFS and significantly reduced odds of transfusion or Hb less than or equal to 8.0 g/dL in anemic patients with NSCLC receiving myelosuppressive chemotherapy.
INTRODUCTION: This study evaluated noninferiority of darbepoetin alfa versus placebo for overall survival (OS) and progression-free survival (PFS) in anemic patients with NSCLC treated to a 12.0-g/dL hemoglobin (Hb) ceiling. METHODS: Adults with stage IV NSCLC expected to receive two or more cycles of myelosuppressive chemotherapy and Hb less than or equal to 11.0 g/dL were randomized 2:1 to blinded 500 μg darbepoetin alfa or placebo every 3 weeks. The primary endpoint was OS; a stratified Cox proportional hazards model was used to evaluate noninferiority (upper confidence limit for hazard ratio [HR] < 1.15). Secondary endpoints were PFS and incidence of transfusions or Hb less than or equal to 8.0 g/dL from week 5 to end of the efficacy treatment period. RESULTS: The primary analysis set included 2516 patients: 1680 were randomized to darbepoetin alfa; 836 to placebo. The study was stopped early per independent Data Monitoring Committee recommendation after the primary endpoint was met with no new safety concerns. Darbepoetin alfa was noninferior to placebo for OS (stratified HR = 0.92; 95% confidence interval [CI]: 0.83‒1.01) and PFS (stratified HR = 0.95; 95% CI: 0.87‒1.04). Darbepoetin alfa was superior to placebo for transfusion or Hb less than or equal to 8.0 g/dL from week 5 to end of the efficacy treatment period (stratified odds ratio = 0.70; 95% CI: 0.57‒0.86; p < 0.001). Objective tumor response was similar between the groups (darbepoetin alfa, 36.4%; placebo, 32.6%). Incidence of serious adverse events was 31.1% in both groups. No unexpected adverse events were observed. CONCLUSIONS: Darbepoetin alfa dosed to a 12.0-g/dL Hb ceiling was noninferior to placebo for OS and PFS and significantly reduced odds of transfusion or Hb less than or equal to 8.0 g/dL in anemic patients with NSCLC receiving myelosuppressive chemotherapy.