First line hormonal treatment (HT) for metastatic breast cancer (MBC) with exemestane (E) or tamoxifen (T) in postmenopausal patients (pts) - A randomized phase III trial of the EORTC Breast Group

Abstract

515 Background: E is an aromatase inactivator, with demonstrated efficacy in MBC progressing under T, which remained standard 1st line HT over decades. The randomized EORTC phase II trial of E vs T, which showed promising activity in 1st line MBC (Ann. Oncol. 2003, 14: 1391–8) was extended in a phase III reported here, aiming at a true comparison of efficacy and tolerability of both drugs. Methods: Postmenopausal MBC pts with ECOG PS ≤2 and measurable, hormone responsive disease (ER &/or PgR + or unknown with disease free interval >2y) previously untreated with HT for MBC, were randomized to receive open label E 25mg or T 20mg daily. One prior chemotherapy (CT) for MBC was permitted. Prior adjuvant T was allowed if treatment free interval exceeded 6 mo. The trial was powered to detect an increase in median progression free survival (PFS, primary endpoint) of 3 mo in favor of E. Secondary endpoints were survival and tolerability. All analyses were intent to treat. Results: 382 pts accrued by 81 centers received E (190 pts) or T (192 pts). Both groups were balanced for median age (62.5), prior adjuvant CT (E 28%, T 29%) or CT for MBC (E 8%, T 7%), hormone receptor status, PS, prior adjuvant T (21% both) and dominant metastatic site (visceral E 48%, T 47%; bone E 35%, T 36%; soft tissue E 17%, T 17%). On 15/12/2003, 286 events (progression or death under treatment) and 136 deaths were reported. The median PFS is significantly longer under E than T (10.9 vs 6.7 months, p 0.04) with an HR of 0.79 (95% CI 0.62 - 0.99) in favor of E. Best response rates (%) under E were CR 7.4, PR 36.8, SD 27.4, PD 18.4, NE (not evaluable) 10.0; under T, CR 2.6, PR 26.6, SD 37.0, PD 27.6, NE 6.2). No pt withdrew due to toxicity. Grade 2–3 toxicities observed in ≥10% were bone pain (E 12%, T 18%), other pain (E 7%, T 14%) and hot flashes (E 5%, T 12%). Conclusions: E is a safe and highly active steroidal aromatase inactivator, superior to T in MBC. In view of its efficacy and excellent tolerance, E represents a good choice as first line therapy in hormone responsive MBC. Its safety profile makes E also attractive for use in the adjuvant and preventive settings. Author Disclosure Employment or Leadership Consultant or Advisory Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration AstraZeneca; Pfizer; Schering-Plough Pfizer