A Phase 2, Randomized, Open-Label Study To Assess the Efficacy of Extended Dose Schedule Administration of Darbepoetin Alfa (DA) in Cancer Patients (pts) with Chemotherapy-Induced Anemia (CIA).
Authors: Schwartzberg Lee , Rearden Timothy , Yee Lorrin , Mirtsching Barry , Charu Veena , Lam Hung , Lillie Tom , Burkes Ronald , Silberstein Peter 
Published: April 2020

Abstract
Cancer pts with CIA may experience decreased quality of life (QOL) and may require red blood cell transfusions (TFNs). DA increases hemoglobin (Hb) to levels recommended by practice guidelines (11 to 13g/dL), thereby reducing TFN requirements and improving QOL. With chemotherapy (CTX) regimens involving various dosing intervals, being able to synchronize DA dose with CTX could be beneficial. This ongoing phase 2, 25-wk, randomized, open-label, multicenter trial compares the efficacy of DA extended dosing schedule (EDS) administration (every 2 wks [Q2W] or every 3 wks [Q3W]) with DA administered weekly (QW) in pts with CIA. Eligible pts were ≥18 years, had nonmyeloid malignancies, were anemic (Hb&lt;11.0g/dL), and were scheduled to receive ≥8 additional wks of CTX administered QW, Q2W (including every 4 wks [Q4W] with visits Q2W), or Q3W. Pts were randomized in a 1:1 ratio to EDS or QW stratified by length of CTX cycle, screening Hb (&lt;10 vs ≥10g/dL), and tumor type (lung/gynecological vs other nonmyeloid malignancies). Pts in the QW arm received DA 150mcg QW regardless of CTX schedule. Pts in the EDS arm received DA either 300mcg Q2W (with QW or Q2W CTX) or 500mcg Q3W. The primary endpoint was change in Hb from baseline (BL) to wk 13; other endpoints included percentage of pts with ≥1 TFN from BL to wk 13, change in pt-reported outcomes (including Functional Assessment of Cancer Therapy-Fatigue [FACT-F]), and safety. This planned interim analysis presents wk 13 data for pts (n=487 of 750 planned) who were randomized on or before January 23, 2006 and could complete ≥13 wks on study. Patient characteristics and efficacy were similar between the 2 groups (Table). To date, the incidence and types of adverse events reported by pts were generally similar between the 2 groups. Only 1 pt (EDS) had a serious thromboembolic event considered related to DA. 16 QW and 12 EDS pts had died as of the interim analysis. Causes of death included disease progression (6 QW, 3 EDS), cardio-respiratory arrest (2 QW), and acute renal failure (2 QW). These interim results suggest that once per CTX cycle dosing with DA may be well-tolerated and effective in these pts.
Table QW EDS n=245 n=242 *Least squares mean; **Last value carried forward; KM: Kaplan-Meier. Mean (SD) Age, yrs 61.9 (12.8) 62.6 (13.2) Most common tumor type (%) Breast (27) Breast (31) % Pts with stage IV cancer 51 52 Mean (SD) BL Hb (g/dL) 10.1 (0.9) 10.2 (0.8) Mean* (99.9%CL) change in Hb (BL-wk 13) [n] (LVCF**) (g/dL) 1.0 (0.7,1.3) [244] 0.9 (0.5,1.2) [241] KM% (99.9%CL) pts who achieved target Hb (≥11g/dL) [n] 78 (68,89) [210] 76 (65,87) [215] Crude% (99.9%CL) pts who achieved target Hb (≥11g/dL) [n] 70 (59,80) [210] 64 (54,75) [215] Mean (SD) Hb after achieving target (g/dL) [n] 11.6 (0.8) [182] 11.7 (0.7) [166] KM% (99.9%CL) pts who had TFNs [n] 21 (12,29) [245] 22 (13,31) [242] Mean* (SE) change in FACT-F [n] 1.6 (0.85) [161] 2.7 (0.84) [168]