Benefit to Longer Chemotherapy in Metastatic Breast Cancer

Charles Bankhead

November/December 2010, Vol 1, No 6 - ESMO 2010 Conference

Milan—Continuing first-line chemotherapy for metastatic breast cancer until disease progression significantly improves overall (OS) and progression free survival (PFS), according to a meta-analysis reported at the 35th ESMO Congress

Prolonged therapy was associated with a 9% reduction in the mortality hazard and a 36% reduction in hazard for progression, and the results should provide information to aid decisionmaking about the duration of chemotherapy for metastatic breast cancer, said researcher Alessandra Gennari, MD, a medical oncologist at Galliera Hospital in Genova, Italy.

“The magnitude of the effect was consistent across all subgroups, suggesting the benefit reflected the impact of the duration of chemotherapy,” said Dr Gennari.

The optimal duration of first-line chemotherapy for metastatic breast cancer has yet to be defined, leaving tolerability to dictate how long therapy continues for most patients.

In an effort to clarify the potential benefits, Dr Gennari and colleagues performed a meta-analysis of 11 published clinical trials comparing different durations of chemotherapy in 2269 patients with newly diagnosed metastatic breast cancer.

The principal objectives were to determine whether continuing chemotherapy beyond a prespecified number of cycles improves PFS and OS.

Benefits and Lingering Questions
Overall, longer duration of chemotherapy was associated with a mortality hazard ratio of 0.91 (P = .04) and a progression hazard ratio of 0.34 (P <.001). By meta-regression analysis, the findings remained independent of the time of randomization, study design, number of chemotherapy cycles in the control arm, and coadministration of endocrine therapy.

Noting lack of evidence for a survival benefit with prolonged chemotherapy in metastatic breast cancer, the National Comprehensive Cancer Network clinical guidelines point out that the potential benefits should be weighed against potentially detrimental effects of longer-duration chemotherapy for every patient.

The survival benefit and reduced risk of progression observed in the meta-analysis provide justification for clinicians to recommend that patients continue chemotherapy until disease progression or until they can no longer tolerate the therapy, said Dr Gennari.

However, she acknowledged that several key issues remain unresolved, including the optimal duration of therapy, planned sequential therapies versus prolonged use of a single agent, the role of targeted therapies in prolonged treatment, and the economics of continuing therapy beyond a predetermined number of cycles