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BIG 1-98: Adjuvant letrozole reduced risk for death, recurrence compared with tamoxifen
Colleoni M. J Clin Oncol. 2011;doi:10.1200/JCO.2010.31.6455.
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Further analysis from the phase 3 BIG 1-98 trial showed that women with breast cancer assigned to letrozole had superior 5-year OS and were less likely to experience recurrence compared with women assigned to tamoxifen.
To assess the efficacy of letrozole after selective crossover, researchers of the Breast International Group (BIG) 1-98 study analyzed 2,463 women assigned to 2.5 mg/day letrozole and 2,459 women assigned to 20 mg/day tamoxifen. All of the patients were postmenopausal women with hormone receptor-positive, early-invasive breast cancer and assigned to their respective treatments from March 1998 to March 2000.
Researchers used inverse probability of censoring weighted modeling to obtain better estimates of relative treatment effects in the presence of selective crossover.
Five-year DFS was 85.6% for letrozole vs. 82.1% for tamoxifen (HR=0.83; 95% CI, 0.74-0.94). Letrozole was slightly but significant statistically superior for 5-year OS, as well, 91.8% vs. 90.4% (HR=0.82; 95% CI, 0.70-0.95). Five-year recurrence-free survival was estimated at 92.4% for letrozole and 89.7% for tamoxifen.
Nearly twelve percent (11.9%) of patients discontinued tamoxifen because of an adverse event vs. 13.6% for letrozole. Incidence of discontinuation was greatest in the first 2 years of treatment for both drugs.
Patients assigned tamoxifen experienced significantly more thromboembolic events, vaginal bleeding, hot flushes and night sweating. Patients in the letrozole group had greater incidence of bone fractures, osteoporosis, arthralgia, vaginal dryness, carpal tunnel syndrome and low-grade cholesterol elevation. Additionally, researchers said there were trends toward greater incidence of myalgia and subjective nervous system or psychiatric events associated with letrozole.
There was a trend toward more ischemic heart disease and other cardiovascular events in the letrozole group, but incidence of overall cardiac events were similar between the groups.
Looking at the differences between the OS estimates, the hazard ratios are not that much different in the three analyses of the data. What is different is that with the IPCW method, the hazard ratios are now statistically significant because the confidence intervals didn't cross one.
With the intent-to-treat analysis, the hazard ratio was not statistically significant. The researchers have accounted for the crossover so now the data looks statistically significant for OS, but many of us had made changes in treatment based on the DFS benefit shown in the initial analysis. These results provide additional support for current practice.
– Amelia Zelnak, MD,
Assistant Professor
of Hematology and Oncology,
Winship Cancer Institute at Emory University of
Medicine, Atlanta
Disclosure: Dr. Zelnak reported no relevant financial disclosures.
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