Early vs Standard Intervention with an Extended Epoetin alfa (EPO) Dose Regimen of 120,000 Units (U) Every 3 Weeks (Q3W) in Chemotherapy (CT)-Induced Anemia: Results for Elderly vs. Younger Patients in a Randomized Clinical Trial.

Abstract

A recently completed randomized open-label multicenter clinical trial in cancer pts with CT-induced anemia showed that an extended dose regimen of EPO 120,000 U administered subcutaneously Q3W effectively maintained hemoglobin (Hb) levels within the range of 11–13 g/dL whether initiated early (Hb of ≥11 and ≤12 g/dL) or at a standard threshold (Hb<11 g/dL)1. As elderly pts are particularly sensitive to the effects of anemia related to CT, we postulated whether this group had outcomes (Hb response, transfusion use, and safety) similar to younger patients following treatment with Q3W EPO. 136 pts with non-myeloid malignancy, CT planned for ≥9 wks, and baseline (BL) Hb ≥11 and ≤12 g/dL were randomized either to early intervention with immediate EPO or to standard intervention with EPO when Hb decreased to <11 g/dL. Drug was held for Hb>13 g/dL and dose reduced for Hb>12 g/dL or increase >1.5 g/dL in any 3-wk period (current labeling recommends Hb not to exceed 12 g/dL). If, at any dosing visit after the 1st EPO dose, Hb decreased to <10.0 g/dL, pts were switched to EPO 40,000 U weekly. The primary efficacy endpoint was Percent Values in Range (PVR; the proportion of weekly Hb levels that were ≥11 and ≤13 g/dL). Reported here is a retrospective subset analysis comparing key efficacy and safety results for elderly (≥65 yrs) vs. younger (<65 yrs) pts enrolled in the prospective study. 62 elderly pts (mITT population; 29 early, 33 standard) and 73 younger pts (mITT; 39 early, 34 standard) were randomized to a treatment group and had ≥1 Hb value. Mean BL Hb was 11.5 g/dL in each of the 4 subgroups. The most common tumor sites were colorectal [elderly early intervention group (n=7, 24%)] and breast [elderly standard intervention group (n=11, 32%)], younger early (n=13, 33%), and younger standard intervention (n=18, 53%). Key efficacy and safety results are shown in the table. Clinically relevant thrombotic vascular events (CRTVEs) included a deep vein thrombosis (DVT) in the elderly early group; 1 DVT and 1 pulmonary embolism (PE) in the elderly standard group; 1 pulmonary artery thrombosis, 2 DVTs, 1 PE, 1 thrombosis NOS, and 1 jugular vein thrombosis among 5 pts in the younger early group; and 2 DVTs, 2 PEs, and 1 thrombosis NOS among 4 pts in the younger standard group. The 4 deaths were attributed to the following causes: acute respiratory failure/progression of COPD (eldery early pt), worsening metastatic gastric cancer/hemorrhage brain metastasis (younger early pt), and lower GI bleed and cardiopulmonary arrest, each in 1 younger standard pt. EPO 120,000 U Q3W initiated early or at a standard threshold resulted in similar efficacy and safety outcomes in elderly vs. younger subsets of cancer pts with CT-induced anemia. 1ASCO 2007 Annual Mtg, Abstract 19564.≥65 Yrs<65 YrsEarly, n=29Standard, n=33Early, n=39Standard, n=34Mean Age ± SD (yrs)71.8±5.773.7±4.852.1±9.748.7±11.1Mean PVR (95% CI)59.8(49.1,70.5)56.8(45.6,68.0)60.0(50.3,69.7)63.1(54.0,72.2)PRBC Transfusion After 4 Wks of EPO, n(%)2(6.9)3(12.0) [of 25 treated pts]4(10.3)1(3.8) [of 26 treated pts]Dose Reduction, n(%)12(41)6(18)17(44)7(21)Dose Withhold, n(%)10(34)4(12)16(41)7(21)CRTVE Pts, n(%)1(3)2(6)5(13)4(12)Death, n(%)1(3)01(3)2(6)PVR, percent values in range; CRTVE, clinically relevant thrombotic vascular event.