Third-generation AIs improve survival among women with advanced breast cancer

Physicians discuss whether the improvement in survival should change the current standard of care.

Issue: November 1, 2006

The use of third-generation aromatase inhibitors vs. standard hormonal therapy was associated with a significant survival improvement among women with advanced breast cancer, according to a meta-analysis of 30 clinical trials.

“This association was apparent in the first-, second- and subsequent-line treatment settings,” said lead researcher Davide Mauri, MD, professor in the department of medical oncology at the University of Ioannina School of Medicine in Greece.

These findings may challenge the current standard of care for first- and second-line treatment, the researchers said in the Journal of the National Cancer Institute.

An accompanying editorial by Catherine H. Van Poznak, MD, argued that, if anything, Mauri and colleagues “underestimated the clinical value of aromatase inhibitor therapy because of the chosen endpoint: prolongation of overall survival.” Van Poznak is an assistant professor in the breast oncology program at the University of Michigan Comprehensive Cancer Center.

“Depletion of estrogen in postmenopausal patients by inhibition of aromatase is clearly a step forward, but there is much to be done and much to be learned,” Van Poznak wrote.

Questioning the standard

Although many research groups have examined the use of aromatase inhibitors among women with breast cancer, the survival benefits to patients compared with standard hormonal therapy have not been precisely quantified in an overview fashion.

Mauri and colleagues performed a meta-analysis of various randomized trials among patients with advanced breast cancer. They compared aromatase inhibitors or inactivators with the standard hormonal treatments in a first- or second-line setting. They also studied whether specific aromatase inhibitors had superior efficacy to standard hormonal therapy.

The researchers searched the Cochrane Central Trials Registry and PubMed databases to identify 30 relevant studies regarding aromatase inhibitors and hormonal treatments. They excluded trials in which randomization was limited to earlier stages of breast cancer. Data from interim analyses were eligible if no further data were available.

They recorded various study data, including the median survival, and any statistically significant differences between arms.

The researchers analyzed data separately according to the generation of the aromatase inhibitor, as well. They also performed various subgroup analyses, depending on the type of hormonal therapy.

Third generation only

There were a total of 8,504 patients eligible from the 30 identified trials: 4,559 had received an aromatase inhibitor or inactivator and the remaining 3,945 had received standard hormonal treatment.

Third-generation aromatase inhibitors and inactivators were associated with increased survival compared with standard hormonal therapy, according to the meta-analysis (95% CI=0.82-0.93). There was no evidence of increased survival with first- and second-generation agents.

The survival benefit for third-generation agents was similar in first-line and second-line trials, which compared aromatase inhibitors with tamoxifen and progestagen, respectively.

“The standard of care may need to be reconsidered,” Mauri said. “Both efficacy and tolerability also need to be taken into account in clinical decision making. The available evidence has suggested that aromatase inhibitors cause less weight gain, dyspnea and peripheral edema than progestins but that they may cause more hot flashes.” – by Rebekah Cintolo

For more information:

Mauri D, Pavlidis N, Polyzos P, et al. Survival with aromatase inhibitors and inactivators versus standard hormonal therapy in advanced breast cancer: meta-analysis. J Natl Cancer Inst. 2006;98:1285-1291.

Van Poznak CH, Hayes DF. Aromatase inhibitors for the treatment of breast cancer: is tamoxifen of historical interest only? J Natl Cancer Inst. 2006;98:1261-1263.