4579 - Randomized, double-blind, placebo (P)-controlled phase 3 noninferiority study of darbepoetin alfa (D) for anemia in patients (pts) with advanced NSCLC: an ad hoc subgroup analysis of pts with baseline hemoglobin (Hb) _10.0 g/dL

Background

In the primary analysis of this study (EudraCT: 2007-005792-34), D dosed to a 12.0-g/dL Hb ceiling was noninferior to P for overall survival (OS) and progression-free survival (PFS) and superior to P for transfusion (TN) or Hb ≤ 8.0 g/dL in anemic pts with advanced NSCLC (screening Hb ≤ 11.0 g/dL).

Methods

Adults with stage IV NSCLC expected to receive ≥2 cycles of myelosuppressive chemotherapy, life expectancy >6 mo, ECOG 0–1, and Hb ≤ 11.0 g/dL were randomized 2:1 to D (500 µg SC) or P Q3W. Pts were stratified by region, histology, and Hb. This ad hoc analysis assessed key study endpoints in pts with baseline Hb ≤ 10.0 g/dL and in subgroups with Hb 9.0–10.0 and <9.0 g/dL. Primary endpoint of the parent study was OS; a Cox proportional hazards model, stratified by randomization factors, was used to evaluate noninferiority (upper confidence limit for hazard ratio [HR] <1.15). Secondary endpoints were PFS (noninferiority) and incidence of TN or Hb ≤ 8.0 g/dL from wk 5 to end of efficacy treatment period (EOETP).

Results

Of 2549 pts enrolled in the trial, 1183 had baseline Hb ≤ 10.0 g/dL (735, Hb 9.0–10.0; 448, Hb < 9.0 g/dL). Pts were well matched between arms for sex, race, and age. Among pts with Hb ≤ 10.0 g/dL, the HRs for OS and PFS were close to 1.0; results were consistent in the subgroups. Odds ratios for TN or Hb ≤ 8.0 g/dL from wk 5 to EOETP were <1.0 and were consistent in the subgroups (Table). TN was more frequent in pts with lower baseline Hb. Safety findings were consistent with previous studies; thrombovascular events were more frequent with D than P (Table).

Conclusions

The results presented here appear mostly consistent with the primary study results, but this ad hoc analysis was not powered to demonstrate noninferiority or superiority, so the results should be interpreted in that context.

Clinical trial identification

NCT00858364; July 17, 2009.

Legal entity responsible for the study

Amgen Inc.

Funding

Amgen Inc.

Editorial Acknowledgement

The authors would also like to acknowledge James Balwit, MS, CMPP (Complete Healthcare Communications, LLC, an ICON plc company, West Chester, PA), whose work was funded by Amgen Inc., and Micah Robinson, PhD (Amgen Inc.), for assistance in writing this abstract.

Disclosure

D. Henry: Grants: Amgen Inc.; Consulting fees: Amag; Editor in Chief of the Journal of Community and Supportive Oncology. K. Kubota: Research grants: Boehringer lngelheim, Ono, Taiho; Consulting fees: Taiho; Speakers' bureau: Chugai, MSD, Boehringer lngelheim, Ono, Taiho, AstraZeneca, Eli Lilly, Kyowa Hakko Kirin, Novartis, Dainippon Sumitomo, Daiichi Sankyo, Eisai. T. Steinmetz: Research grants: Celgene, Novartis; Consulting fees: Amgen Inc., Bristol-Myers Squibb; Speakers' bureau: Amgen Inc., Celgene. G. Thomas: Ownership or partnership: South Carolina Cancer Specialists, P.A.; Consulting fees: Gilead Sciences, Cardinal Health, TRM Oncology, Bayer Oncology; President: South Carolina Oncology Society, 2016–2017; Employee: Hospice Care of the Lowcountry. D. Gordon: Stockholder: Amgen Inc. A.N. Fleishman, C. De Oliveira Brandao: Employee and stockholder: Amgen Inc,. All other authors have declared no conflicts of interest.Table: 1387P

Standardized MedDRA query.

AEs, adverse events; CI, confidence interval; HR, hazard ratio; OR, odds ratio.