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Showing content from https://pubmed.ncbi.nlm.nih.gov/22853014/ below:

Combination anastrozole and fulvestrant in metastatic breast cancer

Clinical Trial

. 2012 Aug 2;367(5):435-44. doi: 10.1056/NEJMoa1201622. Combination anastrozole and fulvestrant in metastatic breast cancer

Affiliations

Affiliation

¹ University of California Irvine Medical Center, Orange, CA 92868, USA. rsmehta@uci.edu

PMID: 22853014
PMCID: PMC3951300
DOI: 10.1056/NEJMoa1201622

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Clinical Trial

Combination anastrozole and fulvestrant in metastatic breast cancer

Rita S Mehta et al. N Engl J Med. 2012.

. 2012 Aug 2;367(5):435-44. doi: 10.1056/NEJMoa1201622. Authors Rita S Mehta¹, William E Barlow, Kathy S Albain, Ted A Vandenberg, Shaker R Dakhil, Nagendra R Tirumali, Danika L Lew, Daniel F Hayes, Julie R Gralow, Robert B Livingston, Gabriel N Hortobagyi Affiliation

¹ University of California Irvine Medical Center, Orange, CA 92868, USA. rsmehta@uci.edu

PMID: 22853014
PMCID: PMC3951300
DOI: 10.1056/NEJMoa1201622

Item in Clipboard

Abstract

Background: The aromatase inhibitor anastrozole inhibits estrogen synthesis. Fulvestrant binds and accelerates degradation of estrogen receptors. We hypothesized that these two agents in combination might be more effective than anastrozole alone in patients with hormone-receptor (HR)-positive metastatic breast cancer.

Methods: Postmenopausal women with previously untreated metastatic disease were randomly assigned, in a 1:1 ratio, to receive either 1 mg of anastrozole orally every day (group 1), with crossover to fulvestrant alone strongly encouraged if the disease progressed, or anastrozole and fulvestrant in combination (group 2). Patients were stratified according to prior or no prior receipt of adjuvant tamoxifen therapy. Fulvestrant was administered intramuscularly at a dose of 500 mg on day 1 and 250 mg on days 14 and 28 and monthly thereafter. The primary end point was progression-free survival, with overall survival designated as a prespecified secondary outcome.

Results: The median progression-free survival was 13.5 months in group 1 and 15.0 months in group 2 (hazard ratio for progression or death with combination therapy, 0.80; 95% confidence interval [CI], 0.68 to 0.94; P=0.007 by the log-rank test). The combination therapy was generally more effective than anastrozole alone in all subgroups, with no significant interactions. Overall survival was also longer with combination therapy (median, 41.3 months in group 1 and 47.7 months in group 2; hazard ratio for death, 0.81; 95% CI, 0.65 to 1.00; P=0.05 by the log-rank test), despite the fact that 41% of the patients in group 1 crossed over to fulvestrant after progression. Three deaths that were possibly associated with treatment occurred in group 2. The rates of grade 3 to 5 toxic effects did not differ significantly between the two groups.

Conclusions: The combination of anastrozole and fulvestrant was superior to anastrozole alone or sequential anastrozole and fulvestrant for the treatment of HR-positive metastatic breast cancer, despite the use of a dose of fulvestrant that was below the current standard. (Funded by the National Cancer Institute and AstraZeneca; SWOG ClinicalTrials.gov number, NCT00075764.).

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Figures
Figure 1. Enrollment, Randomization, and Follow-up

Figure 1. Enrollment, Randomization, and Follow-up
Figure 1. Enrollment, Randomization, and Follow-up
Figure 2. Kaplan–Meier Curves for Progression-free Survival,…

Figure 2. Kaplan–Meier Curves for Progression-free Survival, According to Treatment Group

The overall hazard ratio…

Figure 2. Kaplan–Meier Curves for Progression-free Survival, According to Treatment Group

The overall hazard ratio for progression or death with the combination therapy is shown.

Figure 3. Progression-free Survival, According to Subgroups

Figure 3. Progression-free Survival, According to Subgroups

The hazard ratio for progression or death with…

Figure 3. Progression-free Survival, According to Subgroups

The hazard ratio for progression or death with the combination therapy is shown for each indicated subgroup. The dashed line indicates the overall hazard ratio, and the solid vertical line indicates no difference between treatments. The P values shown for the interaction of each factor with treatment are based on a Cox regression model. HER2 denotes human epidermal growth factor receptor type 2.

Figure 4. Kaplan–Meier Curves for Overall Survival,…

Figure 4. Kaplan–Meier Curves for Overall Survival, According to Treatment Group

The overall hazard ratio…

Figure 4. Kaplan–Meier Curves for Overall Survival, According to Treatment Group

The overall hazard ratio for death with the combination therapy is shown.