Tags

Type your tag names separated by a space and hit enter

Letrozole in the extended adjuvant treatment of postmenopausal women with history of early-stage breast cancer who have completed 5 years of adjuvant tamoxifen.
Clin Cancer Res. 2005 Aug 15; 11(16):5671-7.CC

Abstract

PURPOSE

To present the basis of the decision of the Food and Drug Administration to grant accelerated approval for letrozole for extended adjuvant treatment of early-stage breast cancer in postmenopausal women after completion of adjuvant tamoxifen.

EXPERIMENTAL DESIGN

The Food and Drug Administration reviewed the data from the MA17 trial, a single, multinational, randomized, double-blind, and placebo-controlled trial, submitted by the applicant to support the proposed new indication.

RESULTS

MA17 consisted of a core study and Lipid and Bone Mineral Density safety substudies. It enrolled 5,187 patients. In the core study, median treatment duration was 24 months and median follow-up duration was 27.4 months. Using a conventional definition of disease-free survival, 122 events on letrozole and 193 events on placebo were observed (hazard ratio, 0.62; 95% confidence interval, 0.49-0.78; P = 0.00003). Distant disease-free survival also improved with letrozole, 55 versus 92 events (hazard ratio, 0.61; 95% confidence interval, 0.44-0.84; P = 0.003). No statistically significant improvement in overall survival was observed. Hot flushes, arthralgia/arthritis, myalgia, and new diagnosis of osteoporosis were more common on letrozole. Frequency of fractures and cardiovascular ischemic events was not significantly different. A statistically significant mean decrease in bone mineral density in the hip occurred at 24 months on letrozole.

CONCLUSIONS

Letrozole administration led to a statistically significant prolongation in disease-free survival. Fractures and cardiovascular events were similar to placebo; however, new diagnoses of osteoporosis were more frequent. Short duration of treatment and follow-up precluded assessment of long-term safety and efficacy. Thus, accelerated approval was granted instead of regular approval.

Authors+Show Affiliations

Mann BS
Division of Oncology Drug Products, Center for Drug Evaluation and Research, Food and Drug Administration, Rockville, Maryland 20857, USA. mannb@cder.fda.gov
Johnson JR
No affiliation info available
Kelly R
No affiliation info available
Sridhara R
No affiliation info available
Williams G
No affiliation info available
Pazdur R
No affiliation info available

MeSH

AgedAntineoplastic AgentsAntineoplastic Agents, HormonalAromatase InhibitorsBone DensityBreast NeoplasmsChemotherapy, AdjuvantDisease-Free SurvivalDizzinessDouble-Blind MethodDrug ApprovalFemaleFollow-Up StudiesHeadacheHumansLetrozoleMiddle AgedMulticenter Studies as TopicNeoplasm StagingNitrilesPostmenopauseRandomized Controlled Trials as TopicSkin DiseasesTamoxifenTime FactorsTreatment OutcomeTriazolesUnited StatesUnited States Food and Drug Administration

Pub Type(s)

Journal Article

Language

eng

PubMed ID

16115902

Citation

Mann, Bhupinder S., et al. "Letrozole in the Extended Adjuvant Treatment of Postmenopausal Women With History of Early-stage Breast Cancer Who Have Completed 5 Years of Adjuvant Tamoxifen." Clinical Cancer Research : an Official Journal of the American Association for Cancer Research, vol. 11, no. 16, 2005, pp. 5671-7.
Mann BS, Johnson JR, Kelly R, et al. Letrozole in the extended adjuvant treatment of postmenopausal women with history of early-stage breast cancer who have completed 5 years of adjuvant tamoxifen. Clin Cancer Res. 2005;11(16):5671-7.
Mann, B. S., Johnson, J. R., Kelly, R., Sridhara, R., Williams, G., & Pazdur, R. (2005). Letrozole in the extended adjuvant treatment of postmenopausal women with history of early-stage breast cancer who have completed 5 years of adjuvant tamoxifen. Clinical Cancer Research : an Official Journal of the American Association for Cancer Research, 11(16), 5671-7.
Mann BS, et al. Letrozole in the Extended Adjuvant Treatment of Postmenopausal Women With History of Early-stage Breast Cancer Who Have Completed 5 Years of Adjuvant Tamoxifen. Clin Cancer Res. 2005 Aug 15;11(16):5671-7. PubMed PMID: 16115902.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Letrozole in the extended adjuvant treatment of postmenopausal women with history of early-stage breast cancer who have completed 5 years of adjuvant tamoxifen. AU - Mann,Bhupinder S, AU - Johnson,John R, AU - Kelly,Roswitha, AU - Sridhara,Rajeshwari, AU - Williams,Grant, AU - Pazdur,Richard, PY - 2005/8/24/pubmed PY - 2005/12/22/medline PY - 2005/8/24/entrez SP - 5671 EP - 7 JF - Clinical cancer research : an official journal of the American Association for Cancer Research JO - Clin Cancer Res VL - 11 IS - 16 N2 - PURPOSE: To present the basis of the decision of the Food and Drug Administration to grant accelerated approval for letrozole for extended adjuvant treatment of early-stage breast cancer in postmenopausal women after completion of adjuvant tamoxifen. EXPERIMENTAL DESIGN: The Food and Drug Administration reviewed the data from the MA17 trial, a single, multinational, randomized, double-blind, and placebo-controlled trial, submitted by the applicant to support the proposed new indication. RESULTS: MA17 consisted of a core study and Lipid and Bone Mineral Density safety substudies. It enrolled 5,187 patients. In the core study, median treatment duration was 24 months and median follow-up duration was 27.4 months. Using a conventional definition of disease-free survival, 122 events on letrozole and 193 events on placebo were observed (hazard ratio, 0.62; 95% confidence interval, 0.49-0.78; P = 0.00003). Distant disease-free survival also improved with letrozole, 55 versus 92 events (hazard ratio, 0.61; 95% confidence interval, 0.44-0.84; P = 0.003). No statistically significant improvement in overall survival was observed. Hot flushes, arthralgia/arthritis, myalgia, and new diagnosis of osteoporosis were more common on letrozole. Frequency of fractures and cardiovascular ischemic events was not significantly different. A statistically significant mean decrease in bone mineral density in the hip occurred at 24 months on letrozole. CONCLUSIONS: Letrozole administration led to a statistically significant prolongation in disease-free survival. Fractures and cardiovascular events were similar to placebo; however, new diagnoses of osteoporosis were more frequent. Short duration of treatment and follow-up precluded assessment of long-term safety and efficacy. Thus, accelerated approval was granted instead of regular approval. SN - 1078-0432 UR - https://www.unboundmedicine.com/medline/citation/16115902/Letrozole_in_the_extended_adjuvant_treatment_of_postmenopausal_women_with_history_of_early_stage_breast_cancer_who_have_completed_5_years_of_adjuvant_tamoxifen_ DB - PRIME DP - Unbound Medicine ER -