Abstract P1-12-05: First-line chemotherapy with pegylated liposomal doxorubicin versus capecitabine in elderly patients with metastatic breast cancer: results of the phase III OMEGA study of the Dutch Breast Cancer Trialists' Group (BOOG)
Authors: Smorenburg CH , Seynaeve C , Wymenga MANM , Maartense E , de Graaf H , de Jongh FE , Braun HJ , Los M , Schrama JG , Portielje JEA , Hamaker M , van Tinteren H , de Groot SM , van Leeuwen-Stok EAE , Nortier HWR 
Published: August 2014

Abstract
Background The efficacy and feasibility of chemotherapy in elderly metastatic breast cancer (MBC) patients (pts) have been studied in various phase II studies. However, results of prospective randomized studies in elderly MBC pts are scarce.
Methods In this phase III multicenter study, MBC pts ≥ 65 years eligible for first-line chemotherapy were randomized between pegylated liposomal doxorubicin (PEGdoxo) (45mg/m2, IV, q 4 wks) or capecitabine (Cape) (1000 mg/m2 PO bid, days 1–14, q 3 wks). Other eligibility criteria were ECOG performance status (PS) ≤ 2 (3 allowed if due to pain or pre existing comorbidity), adequate bone marrow and organ functions. Stratification factors were PS (0–1 vs 2–3), HER2 status, visceral/non-visceral disease, adjuvant hormonal therapy (HTx), and HTx for MBC. Baseline geriatric assessment (GA) included functional status, instrumental activities of daily living, cognition, mood, comorbidity, polypharmacy and nutritional status. Chemotherapy was continued for 24 wks in the absence of progressive disease (PD) or unacceptable toxicity. Primary endpoint was progression-free survival (PFS), secondary endpoints were response rate, overall survival (OS), toxicity (CTC criteria) and compliance.
Results Between April 2007 and August 2011, 78 pts were randomized to PEGdoxo (n = 40) or Cape (n = 38). The study was prematurely closed due to slow accrual and supply problems with PEGdoxo. Mean age was 74 years (range 65–86; 75+ 54%; 80+ 13%). Pt characteristics were balanced between the two arms: PS 0–1 77%, ER+ 68%, HER2+ 5%, visceral/non-visceral disease 76%/24%, adjuvant HTx 46%, HTx for MBC 56%, ≥ 3 metastatic sites 50%. Only 22 out of 75 pts with a baseline GA had no geriatric condition (29%), while 32 pts (43%) and 21 pts (28%) had one or ≥ 2 geriatric conditions, respectively. Chemotherapy was given for 6 months in 38%, with a mean dose intensity of 84% in both arms. Reasons for early treatment discontinuation were: PD (31%), toxicity (28%), pt withdrawal (3%). After a median follow up of 32 months, 74 pts had PD and 56 pts had died. The median PFS was 5.7 and 7.7 months with PEGdoxo and Cape (HR 0.68, 95% CI: 0.42–1.11, p = 0.12) and the median OS was 13.8 and 16.8 months, respectively (HR 0.84, 95% CI: 0.49–1.42, p = 0.51). Response was evaluable in 64 pts, with a partial response (PR) in 7 (21%) and 6 pts (19%), and stable disease in 21 (64%) and 17 pts (55%) for PEGdoxo and Cape, respectively. Toxicity was acceptable, mainly being grade 1–2, with for PEGdoxo/Cape grade 1 alopecia in 14/4 pts (grade 2 in 1 PEGdoxo pt), grade 3 fatigue in 5/5 pts, grade 3 HFS in 4/6 pts and grade 3 mucositis in 4/1 pts, respectively. Pts with ≥ 1 geriatric condition more frequently experienced grade 3–4 toxicity, after correcting for type of chemotherapy, age and PS (HR 2.24, 95% CI: 1.21–4.16). Pts aged 75+ had a twofold higher risk of dying, irrespective of treatment arm (HR 2.31, 95% CI: 1.31–4.07).
Conclusions First-line chemotherapy with either PEGdoxo or Cape was feasible in elderly MBC pts, with adequate dose intensity and acceptable toxicity, even in non-fit pts or pts aged 75+. Baseline GA correlated with toxicity.
Citation Information: Cancer Res 2012;72(24 Suppl):Abstract nr P1-12-05.