Table 2.

Recent studies reporting survival data for ESAs in CIA.

Source	Tumor type	Patients (n)	Results
Untch et al., 2011	Breast	733	No effect – DFS, OS
Nagel et al., 2011	SCLC	73	No effect – PFS, OS
Fujisaka et al., 2011	Lung/Gyn	186	No effect – OS
Moebus et al., 2013	Breast	1284	No effect – RFS, OS
Nitz et al., 2014	Breast	1234	No effect – EFS, OS
Mountzios et al., 2016	Solid tumors	630	No effect – PFS, OS
Leyland-Jones et al., 2016	Met breast	2098	No effect – OS; No effect – PFS (independent review)
Nagarkar et al., 2018	NSCLC	2516	No effect – PFS, OS

CIA, chemotherapy-induced anemia; DFS, disease-free survival; EFS, event-free survival; ESAs, erythropoiesis-stimulating agents; Gyn, gynecological; Met, metastatic; NSCLC, non-small cell lung cancer; OS, overall survival; PFS, progression-free survival; RFS, relapse-free survival; SCLC, small cell lung cancer. Untch et al. (2011): randomized Phase 3 trial of chemotherapy in breast cancer with or without darbepoetin (target Hb 12.5–13 g/dL in darbepoetin-treated patients). Addition of darbepoetin resulted in no differences in 3-year disease-free survival and OS. Nagel et al. (2011): randomized Phase 2 study involving chemotherapy in limited or extensive SCLC with or without darbepoetin (target Hb 12–13 g/dL in darbepoetin-treated patients); no differences in PFS or 1-year survival rates reported between treatment arms. Fujisaka et al. (2011): randomized Phase 3 trial of epoetin beta in patients receiving chemotherapy for lung/gynecological cancer (target Hb under 12 g/dL); no difference in 1-year survival rates reported between ESA treated vs. untreated. Moebus et al. (2013): in a second randomization of an intense dose-dense chemotherapy arm, outcome in primary breast cancer with or without addition of epoetin alfa (target Hb 12.5–13 g/dL) was studied. Epoetin treatment had no impact on OS or RFS at median follow-up of 62 months. Nitz et al. (2014): randomized Phase 3 trial in patients with node-positive primary breast cancer receiving chemotherapy with or without darbepoetin alfa. Initially, Hb levels were maintained between 13 and 14 g/dL, but this was modified to 12 g/dL after the label amendment of 2008. At 39 months, darbepoetin treatment had no impact on either EFS or OS. Mountzios et al. (2016): randomized Phase 3 trial investigating administration of ESAs in patients with solid tumors and CIA with a median follow-up of 7 years. Patients in one group received prophylactic ESA with iron supplementation (target Hb 14 g/dL). If Hb levels exceeded 14 g/dL, ESAs were discontinued and resumed when levels were <12 g/dL. In the other group, patients received iron supplementation with ESAs in a Hb-based manner, initiated only if Hb levels were <11 g/dL during chemotherapy, stopping at 13 g/dL. No differences in DFS, PFS, or OS were reported between the two groups with respect to the presence or absence of anemia at entry to study, or the manner in which ESAs were given (prophylactic vs. Hb-based). Leyland-Jones et al. (2016): epoetin alfa in anemic patients receiving chemotherapy for metastatic breast cancer. Patients received either epoetin alfa or best standard of care alongside chemotherapy. ESA treatment had no effect on OS. Although investigator-determined PFS was reported to be decreased by ESAs, an independent review determined PFS was not decreased. Nagarkar et al. (2018): evaluated non-inferiority of darbepoetin alfa (DAR) versus placebo for OS and PFS in anemic patients with NSCLC treated to a 12 g/dL hemoglobin ceiling. Darbepoetin was non-inferior to placebo for OS and PFS and significantly reduced odds of transfusion or hemoglobin ≤ 8 g/dL in anemic patients with NSCLC receiving myelosuppressive chemotherapy.