The number needed to treat (NNT) as a measure of drug efficacy: the case of zoledronic acid for early hormone-responsive breast cancer in the ABCSG-12 trial.

Abstract

Abstract Abstract #2113 Background: Zoledronic acid (ZOL) has demonstrated antitumor and antimetastatic activities in preclinical and early clinical studies in many cancer types. The Austrian Breast and Colorectal Cancer Study Group Trial 12 (ABCSG-12) examined the efficacy of adjuvant therapy in premenopausal women with hormone-responsive early breast cancer receiving goserelin (GOS) + anastrozole (ANA) or tamoxifen (TAM), both ± ZOL. In this trial, ZOL significantly prolonged disease-free survival (DFS) and recurrence-free survival (RFS) versus no ZOL. However, in addition to relative risk reduction, the potential for patients to benefit from a treatment is an important consideration. The number needed to treat (NNT) represents an estimation of the number of patients that have to be treated with an investigational drug for 1 patient to receive clinical benefit within a specific follow-up period. NNT is a powerful, clinically relevant measure of efficacy that can provide a real-world perspective on the efficacy results from clinical trials. Methods: 1,803 patients were randomized to GOS (3.6 mg/28 d SC) + TAM (20 mg/d PO) ± ZOL (4 mg/ 6 mos IV) or GOS + ANA (1 mg/d PO) ± ZOL for 3y. Endpoints at 60 mos for TAM vs ANA and ZOL vs no ZOL were DFS (primary), RFS, overall survival and safety. NNT was calculated for ZOL with respect to DFS and RFS, and compared with other paradigm-changing cancer therapies. Results: After 60 mos median follow-up, ZOL significantly reduced the risk of DFS events by 36% (P = .01) and RFS events by 35% (P = .02) vs no ZOL. For ZOL therapy, NNT = 31 and NNT = 33 to prevent 1 DFS or 1 RFS event respectively at a median follow-up of 60 months. In comparison, the NNT with respect to DFS is 28 for paclitaxel (60-69 months follow-up) and 31 for docetaxel (43-60 months follow-up). Moreover, ZOL was generally well tolerated, and neither ONJ nor renal toxicity was an issue in this setting. Conclusions: The NNT is a simple and effective method to assess clinical trial results that will have relevance to daily practice. In the current comparisons, the NNT for ZOL plus endocrine therapy in ABCSG-12 was similar to the NNTs for taxanes. Therefore the addition of ZOL provides DFS and RFS benefits of magnitudes similar to those from practice-changing chemotherapies like taxanes. Citation Information: Cancer Res 2009;69(2 Suppl):Abstract nr 2113.