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

MedStar author(s):
Citation: Journal of the National Cancer Institute. 2023 May 15PMID: 37184928Institution: Associate Dean for Research Development | MedStar Franklin Square Medical Center | MedStar HealthDepartment: Surgical OncologyForm of publication: Journal ArticleMedline article type(s): Journal ArticleSubject headings: IN PROCESS -- NOT YET INDEXED | Year: 2023Local holdings: Available online from MWHC library: 1996 - present (after 1 year), Available in print through MWHC library: 1999 - 2006ISSN:
  • 0027-8874
Name of journal: Journal of the National Cancer InstituteAbstract: 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.CLINICAL TRIALS REGISTRATION: NCT00382070. Copyright The Author(s) 2023. Published by Oxford University Press. All rights reserved. For permissions, please email: [email protected]: 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.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.All authors: Bandos H, Brufsky AM, Chia SK, Dakhil SR, Fehrenbacher L, Geyer CE, Jeong JH, Lembersky BC, Mamounas EP, McCarron EC, Rastogi P, Soori GS, Swain SM, Wade JL, Walshe JM, Wolmark NOriginally published: Original year of publication: 2023Fiscal year: Fiscal year of original publication: FY2023Digital Object Identifier:
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Item type Current library Collection Call number Status Date due Barcode
Journal Article MedStar Authors Catalog Article 37184928 Available 37184928

Available online from MWHC library: 1996 - present (after 1 year), Available in print through MWHC library: 1999 - 2006

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.

CLINICAL TRIALS REGISTRATION: NCT00382070. Copyright The Author(s) 2023. Published by Oxford University Press. All rights reserved. For permissions, please email: [email protected].

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.

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.

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