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
- Onconephrology: Clinical and Research Advances - II
November 05, 2022 | Location: Exhibit Hall, Orange County Convention Center‚ West Building
Abstract Time: 10:00 AM - 12:00 PM
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 –