[3] Trastuzumab prolongs progression-free survival in hormone-dependent and HER2-positive metastatic breast cancer.

Mackey JR, Kaufman B, Clemens M, Bapsy PP, Vaid A, Wardley A, Tjulandin S, Jahn M, Lehle M, Jones A.. Cross Cancer Institute, Edmonton, Canada; Chaim Sheba Medical Center, Tel Hashomer, Israel; Krankenanstalt Mutterhaus der Borromaerinnen, Trier, Germany; Kidwai Memorial Institute of Oncology, Bangalore, India; Rajiv Gandhi Cancer Institute, New Delhi, India; Christie Hospital NHS Trust, Manchester, United Kingdom; Russian Cancer Research Center, Moscow, Russian Federation; F Hoffmann-La Roche, Basel, Switzerland; Royal Free Hospital, London, United Kingdom

Background: Recent studies have shown that 45-50% of human epidermal growth factor receptor 2 (HER2)-overexpressing breast cancers (BCs) are also oestrogen-receptor (ER) positive (Eur J Cancer 2001;37:S160; NEJM 2005;353:1659-72; NEJM 2005;353:1673-84). The evidence of crosstalk between HER2 and ER signalling pathways in BC suggests that combining treatments that target these different pathways may improve outcomes over monotherapy. The randomised, controlled, open-label, multicentre, Phase III TAnDEM study was performed to evaluate the efficacy and safety of trastuzumab (H) plus anastrozole (A) compared to A alone in postmenopausal women with HER2-positive and ER- and/or progesterone receptor (PgR)-positive metastatic BC (MBC).
Methods: Eligible patients (pts) were postmenopausal with HER2-positive (IHC 3+ and/or FISH+) and ER- and/or PgR-positive MBC. Pts were randomised to A only (1 mg/day po) or A+H (4 mg/kg iv infusion on Day 1 then 2 mg/kg qw) until progressive disease (PD). The primary end point was progression-free survival (PFS).
Results: Overall, 207/208 randomised pts received treatment: 104 in the A arm and 103 in the A+H arm. Pts in the A+H arm had significant improvements in PFS (4.8 vs 2.4 months; p=0.0016), clinical benefit rate (CBR; 42.7% vs 27.9%; p=0.026) and time to progression (TTP; 4.8 vs 2.4 months; p=0.0007) compared to pts in the A arm. The overall response rate (ORR) in 147 evaluable pts (A: 73, A+H: 74) was significantly higher with A+H compared to A only (20.3% vs 6.8%; p=0.018). Overall survival (OS) was prolonged (28.5 vs 23.9 months; p=0.325) with A+H compared to A only despite crossover of more than half of pts in the A arm to receive H upon PD. Exploratory analyses of centrally confirmed hormone-receptor-positive pts (n=150; A: 73, A+H: 77) showed that pts in this subgroup had a longer median PFS in both arms, which was still significantly longer in the A+H arm than in the A arm (5.6 vs 3.8 months; p=0.006). An additional exploratory analysis showed that among 145 pts without liver metastases (A: 75, A+H: 70), those who received A+H had significantly longer OS (41.3 vs 32.1 months; p=0.04) and PFS (7.7 vs 3.8 months; p=0.0006) compared to pts in the A arm.
Conclusions: Combination of A+H in first-line treatment of women with ER- and/or PgR-positive, HER2-positive MBC leads to doubling of PFS and significant improvements in CBR, TTP and ORR compared to treatment with A alone. OS was longer in the A+H arm despite crossover of more than half of pts in the A arm to receive H upon PD.

Thursday, December 14, 2006 10:15 AM

General Session 1 (9:45 AM-11:00 AM)