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

Background

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.

Methods

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.

Results

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.

Conclusions

Oral roxadustat was non-inferior to subcutaneous rHuEPO-α for anemia in patients with non-myeloid malignancies receiving multi-cycle treatments of myelosuppressive chemotherapy.

Clinical trial identification

FGCL-4592-898.

Editorial acknowledgement

Marjet Heitzer, PhD, Kay Square Scientific, Newtown. Square, PA

Legal entity responsible for the study

FibroGen, Inc.

Funding

FibroGen, Inc.

Disclosure

S. Lu: Financial Interests, Speaker, Consultant, Advisor, speaker fees, advisor/consultant: AstraZeneca; Financial Interests, Speaker, Consultant, Advisor, speaker fees: Hansoh, Hengrui Therapeutics; Financial Interests, Speaker, Consultant, Advisor, advisor/consultant: Pfizer, Boehringer Ingelheim, Hutchison, ZaiLab, GenomiCare, Yuhan Corporation, Menarini, InventisBio Co., Simcere Zaiming, Roche; Financial Interests, Research Funding, research support: AstraZeneca, Hutchison, BMS, Heng Rui, BeiGene, Roche, Hansoh, Lilly Suzhou, Fibrogen. J. Wu: Financial Interests, Advisory Role: AstraZeneca, Roche, Novartis, Heng Rui, Lilly, FibroGen; Financial Interests, Other, consultant: AstraZeneca, Roche, Novartis, Heng Rui, Lilly, FibroGen. J. Jiang: Financial Interests, Research Funding: Heng Rui, Roche, Alphamab Oncology, FibroGen. Q. Guo: Financial Interests, Advisory Role: AstraZeneca, Roche, Novartis, Heng Rui, Lilly, FibroGen; Financial Interests, Other, consultant: AstraZeneca, Roche, Novartis, Heng Rui, Lilly, FibroGen. Y. Liu: Financial Interests, Speaker, Consultant, Advisor: Xinda, BeiGene, Roche, Hengrui Therapeutics, AstraZeneca, Qilu, BMS, Roche; Financial Interests, Research Funding: AstraZeneca, BeiGene, Roche, FibroGen. H. Zhang: Financial Interests, Advisory Role: AstraZeneca, Roche, Pfizer, Heng Rui, BMS, BeiGene, Roche, Innovent; Financial Interests, Other, consultant: AstraZeneca, Pfizer, Heng Rui, BMS, BeiGene, Roche, Innovent; Financial Interests, Officer, consultant: Roche. L. Qian: Financial Interests, Research Funding: GSK Plc, Sanofi, Mundi Pharma, Hutchison Whampoa Limited (HWL), Dalian Wanchun Biotechnology Co., Ltd., Shanghai Lunsheng Pharmaceutical Technology Co., Ltd., Innovent (Suzhou), FibroGen. X. Dai: Financial Interests, Research Funding: Luye Pharma, FibroGen. Y. Xie: Financial Interests, Other, speaker fees: AstraZeneca, Roche, Heng Rui, Lilly, Pfizer, MSD, Simcere, FibroGen. T. Fu: Financial Interests, Advisory Role: Heng Rui, Ji Shi, FibroGen; Financial Interests, Other, consultant: Heng Rui, Ji Shi, FibroGen. T. Lee, Y. Lu, R. Ma, M. Eisner: Financial Interests, Full or part-time Employment: FibroGen; Financial Interests, Stocks or ownership: FibroGen.. All other authors have declared no conflicts of interest.