As the Avastin (bevacizumab) drama continues at the FDA, the National Comprehensive Cancer Network (NCCN) has weighed in. The NCCN’s 2011 Guidelines for Breast Cancer continue to recommend Avastin in metastatic breast cancer, despite the FDA’s move toward revoking the indication. Addressing another hot-button oncology issue, the updated guidelines do not recommend routine CYP2D6 testing prior to tamoxifen treatment. The 2011 guideline updates were presented at the NCCN 16th Annual Conference, which took place from March 9-13 in Hollywood, Florida.
In February 2008, Avastin received accelerated approval for the treatment of HER2-positive metastatic breast cancer, based on clinical trial data showing it improved progression-free survival (PFS) by 5.5 months. Full approval was contingent on follow-up trials further supporting Avastin’s efficacy and safety; however, the PFS advantage in 2 major follow-up studies—while still positive—was far lower than what was reported in the original trials, and there was no overall survival benefit. Avastin was also associated with increased toxicity. The FDA’s Oncologic Drugs Advisory Committee subsequently voted 12 to 1 in July 2010 to revoke Avastin’s breast cancer indication.
As the agency moves toward enacting the panel’s recommendation, it has granted Avastin manufacturer Genentech a hearing on June 28 and 29. Genentech’s major argument against revocation will likely be that even though the follow-up trials underperformed and demonstrated no survival benefit, Avastin still improved PFS in some women with metastatic breast cancer.
The NCCN used similar logic in maintaining its Avastin recommendation. Their 2011 Guidelines for Breast Cancer continue to support Avastin use, based on the PFS benefit demonstrated in the major Avastin trials.
Various clinical studies have identified the enzyme CYP2D6 as a potential biomarker for tamoxifen efficacy in patients with early-stage, endocrine-responsive breast cancer; however, 2 major retrospective studies have placed severe doubt on the prognostic value of CYP2D6.
Subanalyses of the Breast International Group (BIG) 1-98 and the Arimidex, Tamoxifen, Alone or in Combination (ATAC) trials found no association between CYP2D6 status and breast cancer–free survival in patients treated with tamoxifen. Based on the entirety of available data, the 2011 NCCN Guidelines for Breast Cancer do not recommend standard CYP2D6 genotyping in evaluating treatment with tamoxifen.
The complete NCCN Guidelines for breast and other cancers are available at www.nccn.org