LBA96 Roxadustat for chemotherapy-induced anemia in patients with non-myeloid malignancies: A randomized, open-label, active-controlled, phase III study

Chemotherapy-induced anemia (CIA) is a common complication of cancer and an important risk factor leading to poor prognosis for patients. Recombinant human erythropoietin-α (rHuEPO-α) is standard of care for CIA; however, safety concerns remain. Roxadustat is the first hypoxia-inducible factor prolyl hydroxylase inhibitor approved for treatment of anemia in chronic kidney disease. This study evaluated the efficacy and safety of roxadustat for anemia in patients with non-myeloid malignancies receiving multi-cycle treatments of myelosuppressive chemotherapy. In this open-label, non-inferiority, multicenter Phase III study conducted in China, patients were randomized (1:1) to receive oral roxadustat or subcutaneous rHuEPO-α three times weekly (TIW) for 12 weeks. Roxadustat starting dosage was 100 mg, 120 mg, and 150 mg TIW (patients weighing 40‒<50, 50–60, and >60 kg). rHuEPO-α starting dosage was 150 IU/kg TIW. Both roxadustat and rHuEPO-α dosages could be modified to achieve hemoglobin (Hb) concentrations of 100–120 g/L. Primary efficacy endpoint was least-squares mean (LSM) change in Hb concentration from baseline to the concentration averaged over Weeks 9‒13. Adverse events (AEs) were monitored. Of 159 patients randomized (n=82, roxadustat; n=77, rHuEPO-α), 140 were included in the per protocol set (n=78, roxadustat; n=62, rHuEPO-α). The LSM (95% 2-sided confidence interval [CI]) change from baseline to Weeks 9‒13 in Hb concentration was 17.1 (13.58, 20.71) g/L with roxadustat and 15.4 (11.34, 19.50) g/L with rHuEPO-α. The lower bound of the 1-sided 97.5% CI for the treatment difference (‒3.4 g/L) was greater than the predefined non-inferiority margin of ‒6.6 g/L, establishing non-inferiority. Results were supported by key secondary endpoints. AE rates were generally comparable between treatments and consistent with previous findings, supporting a positive benefit-risk profile. Oral roxadustat was non-inferior to subcutaneous rHuEPO-α for anemia in patients with non-myeloid malignancies receiving multi-cycle treatments of myelosuppressive chemotherapy.