Updated NCCN Guidelines for Breast Cancer outline expanded treatment options

Women with metastatic breast cancer have expanded treatment options for treating the disease and in the prevention of skeletal-related events as outlined in the recently updated NCCN Guidelines^™ for Breast Cancer. Robert W. Carlson, MD, of Stanford Comprehensive Cancer Center and chair of the NCCN Guidelines Panel for Breast Cancer, presented these and other notable updates to the NCCN Guidelines at the NCCN 16^th Annual Conference on March 10, 2011.

“The efficacy of tamoxifen therapy for the treatment of breast cancer varies widely among individuals, which has led to several trials trying to determine whether there is an association between the CYP 2D6 genotype and the effectiveness of tamoxifen in preventing breast cancer recurrence”

Eribulin (Halaven^™, Eisai Inc.) was added to the NCCN Guidelines as a preferred single agent option in the treatment of metastatic disease, noted Dr. Carlson. Eribulin received FDA approval for the treatment of metastatic breast cancer in patients who received at least two prior chemotherapy regiments for late-stage disease, based on results from a phase 3 study. The study showed that eribulin provided statistically significant overall survival improvements in metastatic breast cancer patients previously treated with an anthracycline and a taxane.

"Considering there are limited options for women with metastatic breast cancer who have already received other therapies, this is a noteworthy treatment option that the Panel felt was important to incorporate into the Guidelines," said Dr. Carlson.

For patients with breast cancer whose disease has metastasized to their bones, the updated NCCN Guidelines now include denosumab (XGEVA^™, Amgen) as an option for the prevention of skeletal-related events, such as fractures and bone pain. Denosumab was approved by the FDA following the results of a study comparing denosumab and zoledronic acid (Zometa^®, Novartis Oncology) finding denosumab to be at least as efficacious as zoledronic acid in preventing skeletal-related events.

"Skeletal complications as a result of bone metastases can be a major source of pain and significantly decrease the quality of life of a patient with cancer. The weakened bones can lead to fractures and compression of the spinal cord and necessitate procedures like surgery and radiation underscoring the need for additional treatment options," said Dr. Carlson.

Dr. Carlson emphasized the importance of biomarkers as key predictors of cancer outcomes, particularly in breast cancer.

"By identifying the presence of biomarkers in breast tumors, health care providers are better able to prescribe effective, personalized treatments that are more likely to result in positive outcomes for patients," said Dr. Carlson.

Three biomarkers have historically been used in breast cancer care: estrogen receptor (ER), progesterone receptor (PR), and HER2. These markers have been a reliable guide for treatment and predictor of breast cancer outcomes; however, several emerging biomarkers, such as the CYP 2D6 genotype to determine tamoxifen (Soltamox^™, AstraZeneca Pharmaceuticals, LP) efficacy, are also being researched extensively.

"The efficacy of tamoxifen therapy for the treatment of breast cancer varies widely among individuals, which has led to several trials trying to determine whether there is an association between the CYP 2D6 genotype and the effectiveness of tamoxifen in preventing breast cancer recurrence," said Dr. Carlson.

Dr. Carlson stressed that the NCCN Guidelines Panel feels that the available studies examining CYP 2D6 are inconsistent, therefore the Panel does not recommend routine testing for CYP 2D6 genotype.

Continuing to capture public interest and attention, Dr. Carlson reviewed the research and evidence leading to the decision for the NCCN Guidelines Panel to reaffirm its existing recommendation of bevacizumab (Avastin^®, Genentech/Roche) in combination with paclitaxel (Taxol^®, Bristol-Myers Squibb Company) as an appropriate therapeutic option for metastatic breast cancer.

The findings in the first large, randomized study of bevacizumab in combination with paclitaxel chemotherapy demonstrated an improvement in disease control and response, but no survival advantage compared with chemotherapy alone and led to both FDA approval of the combination and the addition of the combination to the NCCN Guidelines. Subsequently, several additional studies have been reported that also demonstrate a small disease control advantage with bevacizumab in combination with chemotherapy, but no survival advantage. On the basis of these studies, the NCCN Guidelines Panel continues to include the combination of bevacizumab and paclitaxel as an option. The Panel is less supportive of other chemotherapy agents in combination with bevacizumab.

The Panel revised the related footnote, which now states, "Randomized clinical trials in metastatic breast cancer document that the addition of bevacizumab to some first or second line chemotherapy agents modestly improves time to progression and response rates but does not improve overall survival. The time to progression impact may vary among cytotoxic agents and appears greatest with bevacizumab in combination with weekly paclitaxel."

The NCCN Guidelines are developed and updated through an evidence-based process with explicit review of the scientific evidence integrated with expert judgment by multidisciplinary panels of expert physicians from NCCN Member Institutions. The most recent version of this and all the NCCN Guidelines are available free of charge at NCCN.org. The NCCN Guidelines for Patients^™: Breast Cancer is available at NCCN.com.