ASN's Mission

To create a world without kidney diseases, the ASN Alliance for Kidney Health elevates care by educating and informing, driving breakthroughs and innovation, and advocating for policies that create transformative changes in kidney medicine throughout the world.

learn more

Contact ASN

1401 H St, NW, Ste 900, Washington, DC 20005

email@asn-online.org

202-640-4660

The Latest on Twitter

Kidney Week

Abstract: SA-PO115

On-Treatment Cancer Safety Events With Daprodustat vs. Erythropoiesis-Stimulating Agents: Post Hoc Analyses of ASCEND-ND and ASCEND-D

Session Information

Category: Onconephrology

  • 1600 Onconephrology

Authors

  • Singh, Ajay K., Brigham and Women's Hospital, Boston, Massachusetts, United States
  • McCausland, Finnian R., Brigham and Women's Hospital, Boston, Massachusetts, United States
  • Claggett, Brian, Brigham and Women's Hospital, Boston, Massachusetts, United States
  • Wanner, Christoph, University Hospital of Würzburg, Würzburg, Germany
  • Wiecek, Andrzej, Slaski Uniwersytet Medyczny w Katowicach, Katowice, Slaskie, Poland
  • Atkins, Michael B., Georgetown-Lombardi Comprehensive Cancer Center, Washington DC, District of Columbia, United States
  • Carroll, Kevin, KJC Statistics Limited, Cheshire, United Kingdom
  • Perkovic, Vlado, The University of Sydney Faculty of Medicine and Health, Sydney, New South Wales, Australia
  • McMurray, John, University of Glasgow, Glasgow, Glasgow, United Kingdom
  • Wittes, Janet, WCG Statistics Collaborative, Washington, District of Columbia, United States
  • Snapinn, Steven M., Seattle- Quilcene Biostatistics, Seattle, Washington, United States
  • Blackorby, Allison, GlaxoSmithKline plc, Collegeville, Pennsylvania, United States
  • Barker, Tara, GlaxoSmithKline plc, Collegeville, Pennsylvania, United States
  • Dimino, Tara L., GlaxoSmithKline plc, Collegeville, Pennsylvania, United States
  • Mallett, Stephen, GlaxoSmithKline plc, Collegeville, Pennsylvania, United States
  • Meadowcroft, Amy M., GlaxoSmithKline plc, Collegeville, Pennsylvania, United States
  • Cobitz, Alexander Ralph, GlaxoSmithKline plc, Collegeville, Pennsylvania, United States
  • Solomon, Scott D., Brigham and Women's Hospital, Boston, Massachusetts, United States
Background

Prespecified on-treatment analyses of ASCEND-ND (NCT02876835) raised concerns for a higher relative risk of cancer-related adverse events (AE) with daprodustat (dapro; a hypoxia inducible factor-prolyl hydroxylase inhibitor) vs darbepoetin (darbe) in patients with anemia of CKD. This was not observed in dialysis patients in ASCEND-D (NCT02879305). As there may be a long latency between onset and diagnosis of cancer AE, we performed post-hoc analyses to estimate risks over time.

Methods

ASCEND-ND randomized 3,872 patients to dapro or darbe. ASCEND-D randomized 2,964 patients to dapro or ESAs. Both were open-label; ESA comparators used different dosing intervals (3/week, 1/week, every 2 or every 4 weeks). Cancer-related AE were identified by predefined medical dictionary for regulatory activities terms. The pre-specified approach examined relative risks for cancer AE up to one day after the last dose date (LDD) of randomized therapy. The present analyses used Cox models, adjusted for baseline ESA use and region, to estimate dapro effects by various follow-up periods (censoring at LDD, LDD+dosing intervals, or end of study).

Results

In ASCEND-ND, the effect estimate of dapro vs darbe for cancer-related AE depended on the length of follow-up time after LDD (Fig 1): hazard ratios 1.04 (95%CI 0.77–1.40) at end of study; 1.12 (95%CI 0.81–1.56) for LDD+dosing interval; 1.50 (95%CI 1.04–2.15) for LDD+1 day. These variations were not seen in ASCEND-D, where shorter ESA dosing intervals were more comparable to dapro.

Conclusion

Prespecified on-treatment analyses for cancer-related AE appeared to result in biased estimates of risk in ASCEND-ND, as they preferentially excluded events from patients in the darbe arm. Analyses that account for longer darbe dosing intervals, plus analyses that extend duration of follow-up, may provide a more valid estimate of risk. These resulted in attenuation of effect estimates towards neutrality, similar to ASCEND-D.

Funding

  • Commercial Support