Extended analysis of BIG trial results confirms drug benefits

SAN ANTONIO-Investigators from the Breast International Group 1-98 study and the Intergroup Exemestane Study updated their respective trial results at SABCS 2009. From the BIG 1-98 data, letrozole continued to show a survival advantage, while exemestane offered protective benefits, based on IES study results.

Crossover analysis supports improved OS with Femara

A significant survival benefit was seen with letrozole (Femara) in postmenopausal women with hormone receptor-positive early breast cancer, according to a supportive analysis of the BIG 1-98 trial. This latest analysis updates results presented at SABCS 2008 and adjusts for potential bias resulting from the selective crossover of patients from tamoxifen to letrozole (abstract 16).

In the BIG 1-98 trial, 4,922 breast cancer patients were randomly assigned to one of four treatment regimens:
• Tamoxifen only for five years
• Letrozole only for five years
• Tamoxifen for two years followed by letrozole for three years
• Letrozole for two years followed by tamoxifen for three years

The current Inverse Probability of Censoring Weighted (IPCW) study estimated the clinical benefit of letrozole that may still have been observed without the selective crossover. The results showed that at five years, postsurgical letrozole improved disease-free survival by 15% (P < .05) and overall survival (OS) by 17% (P < .05).

The goal of IPCW analysis is to provide a more accurate estimate of the clinical benefit of a therapy, said study coauthor Meredith Regan, ScD, from Boston’s Harvard Medical School.

Benefit of adjuvant endocrine therapy switch upheld

The IES demonstrated that postmenopausal women with early breast cancer derived protective benefits when they switched to exemestane (Aromasin) from tamoxifen (N Engl J Med 350:1081-1092, 2004; Lancet 369:559-570, 2007).

In this 2009 analysis, the researchers looked at data from patients who were disease- free aft er two to three years of adjuvant tamoxifen therapy. The patients were then randomized to either continue on their treatment course or switch to exemestane for a total of five years of therapy. At the time of the analysis, the median follow up was 91 months, and 91% of surviving patients had at least six years of follow up. The analysis focused on 4,052 patients (out of 4,724) who were either ER-positive or had an unknown ER status (abstract 12).

According to the results, 933 breast cancer- free survival (BCFS) events had been reported in patients receiving exemestane in the ER-positive and unknown group (P = .001). An analysis that was done 2.5 years postrandomization showed that the on-treatment BCFS benefit of switching to exemestane was maintained after treatment. OS was better with exemestane (352 deaths) than tamoxifen (504 deaths).