Ten-year Update: NRG Oncology/NSABP B-42 Randomized Trial: Extended Letrozole Therapy in Early-stage Breast Cancer

Autor: Eleftherios P Mamounas, Hanna Bandos, Priya Rastogi, Barry C Lembersky, Jong-Hyeon Jeong, Charles E Geyer, Louis Fehrenbacher, Stephen K Chia, Adam M Brufsky, Janice M Walshe, Gamini S Soori, Shaker R Dakhil, James L Wade, Edward C McCarron, Sandra M Swain, Norman Wolmark
Rok vydání: 2023
Předmět:
Zdroj: JNCI: Journal of the National Cancer Institute.
ISSN: 1460-2105
0027-8874
DOI: 10.1093/jnci/djad078
Popis: Background NSABP B-42 evaluated extended letrozole therapy (ELT) in postmenopausal breast cancer patients who were disease-free after 5 years of aromatase inhibitor-based (AI) therapy. Seven-year results demonstrated a non-statistically significant trend in disease-free survival (DFS) in favor of ELT. We present 10-year outcome results. Methods In this double-blind, phase 3 trial, patients with stage I-IIIA hormone receptor-positive breast cancer, disease-free after 5 years of an AI or tamoxifen followed by an AI, were randomized to 5 years of letrozole or placebo. Primary endpoint was DFS, defined as time from randomization to breast cancer recurrence, second primary malignancy, or death. All statistical tests are two-sided. Results Between 09/06 and 01/10, 3,966 patients were randomized (letrozole: 1,983; placebo: 1,983). Median follow-up time for 3,923 patients included in efficacy analyses was 10.3 years. There was statistically significant improvement in DFS in favor of letrozole compared to placebo (Hazard Ratio [HR]=0.85; 95%CI 0.74-0.96, p-value = 0.01, 10-year DFS: placebo = 72.6%, letrozole = 75.9%, absolute difference 3.3%). There was no difference in the effect of letrozole on overall survival (OS) (HR = 0.97, 95%CI 0.82-1.15, p-value = 0.74). Letrozole significantly reduced breast cancer-free interval (BCFI) events (HR = 0.75, 95%CI 0.62-0.91, p-value = 0.003, absolute difference in cumulative incidence: 2.7%) and distant recurrences (DR) (HR = 0.72, 95%CI 0.55-0.92, p-value = 0.01, absolute difference: 1.8%). The rates of osteoporotic fractures and arterial thrombotic events did not differ between treatment groups. Conclusions The beneficial effect of ELT on DFS persisted at 10 years. Letrozole also significantly improved BCFI and DR without improving OS. Careful assessment of potential risks and benefits is necessary for selecting appropriate candidates for ELT. Clinical Trials registration NCT00382070
Databáze: OpenAIRE
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