A randomized, open-label, active-controlled phase III study published on October 1, 2024 in the Journal of Clinical Oncology evaluated the efficacy and safety of roxadustat for treating chemotherapy-induced anemia (CIA) in patients with nonmyeloid malignancies. The study, conducted at 44 sites in China and funded by FibroGen (China) Medical Technology Development Co, Ltd, aimed to assess roxadustat as a potential new oral treatment option for CIA.
The study included 159 adult patients (≥18 years) with nonmyeloid malignancies and CIA who were receiving multicycle chemotherapy treatments. Key inclusion criteria were a hemoglobin (Hb) level ≤100 g/L at screening with a ≥10 g/L decrease after chemotherapy initiation, planned concurrent myelosuppressive chemotherapy for ≥8 additional weeks, ferritin ≥50 ng/mL, and transferrin saturation ≥10%. Patients were excluded if they were receiving potentially curative chemotherapy, had significant cardiac disease, or experienced a thromboembolic event within 6 months of screening.
Participants were randomized 1:1 to receive either oral roxadustat or subcutaneous recombinant human erythropoietin-α (rHuEPO-α) three times a week for 12 weeks. Roxadustat starting doses were weight-based (100, 120, or 150 mg), while rHuEPO-α was initiated at 150 IU/kg for all patients. The primary endpoint was the least-squares mean (LSM) change in Hb concentration from baseline to the average over weeks 9-13.
Of the 159 randomized patients, 140 were included in the per-protocol set (roxadustat, n=78; rHuEPO-α, n=62). The study population had a mean age of 59.7 years, with slightly more females and patients with BMI <25 kg/m2 in the roxadustat group. Baseline Hb levels were similar between groups (roxadustat: 89.8 g/L; rHuEPO-α: 91.0 g/L).
The primary efficacy analysis demonstrated noninferiority of roxadustat to rHuEPO-α. The LSM change in Hb from baseline to weeks 9-13 was 17.1 g/L for roxadustat and 15.4 g/L for rHuEPO-α, with a treatment difference of 1.7 g/L (95% CI: -3.39 to 6.84). The lower bound of the confidence interval (-3.39 g/L) was greater than the predefined noninferiority margin of -6.6 g/L. Both groups achieved and maintained the target Hb of 100-120 g/L from week 5 onwards.
Secondary endpoints further supported the efficacy of roxadustat. A higher percentage of patients in the roxadustat group achieved a ≥10 g/L increase in Hb (88.5% vs 82.3%), and fewer patients required red blood cell transfusions. Patient-reported outcomes for quality of life were also noninferior for roxadustat compared to rHuEPO-α.
The safety profile of roxadustat was generally comparable to rHuEPO-α and consistent with previous findings. The incidence of treatment-emergent adverse events (TEAEs) was similar between groups (roxadustat: 95.1%; rHuEPO-α: 93.2%). While there were more deaths in the roxadustat group (9 vs 2), none were considered related to the study drug by investigators. The study authors noted that confounding factors, such as disease progression and COVID-19 infections, may have contributed to this imbalance.
The study had several limitations, including its open-label design, relatively short treatment duration, and lack of power to detect significant differences in adverse events. The COVID-19 pandemic also impacted study conduct, potentially affecting compliance and follow-up visits. Additionally, the high discontinuation rate in the rHuEPO-α group may have led to underreporting of adverse events in that arm.
The authors concluded that roxadustat was noninferior to rHuEPO-α in treating CIA in patients with nonmyeloid malignancies receiving multicycle chemotherapy. They highlighted the potential advantages of roxadustat, including its oral formulation, which may improve patient compliance and avoid costs associated with infusion and cold chain supply.
This study has significant potential clinical impacts. If approved, roxadustat could represent a new treatment paradigm for CIA, offering an oral alternative to injectable erythropoiesis-stimulating agents. The convenience of an oral medication may increase treatment accessibility and compliance, particularly in areas with limited healthcare resources. Furthermore, the distinct mechanism of action of roxadustat, which mimics the body's natural response to anemia, may offer advantages in patients with inflammation or iron deficiency.
However, larger, long-term studies are needed to confirm these findings and further evaluate the safety profile of roxadustat in cancer patients. Additionally, while this study was conducted in China, further research is required to determine if these results are generalizable to other populations. As CIA remains a significant problem in cancer care, affecting quality of life and potentially treatment outcomes, the development of new therapeutic options like roxadustat could have far-reaching implications for oncology practice worldwide.
References
Lu S, Wu J, Jiang J, et al. Efficacy and Safety of Roxadustat for Anemia in Patients Receiving Chemotherapy for Nonmyeloid Malignancies: A Randomized, Open-Label, Active-Controlled Phase III Study. J Clin Oncol. 2025;43(2):143-153. doi:10.1200/JCO.23.02742
