Approximately 15% to 20% of patients with breast cancer have HER2-positive disease. The American Society of Clinical Oncology (ASCO) released new clinical practice guidelines for the treatment of women with advanced HER2-positive breast cancer, focusing on systemic therapies (Giordano SH, et al. J Clin Oncol. 2014 May 5. Epub ahead of print). The guideline recommendations are summarized in the Table.
The treatment of HER2-positive breast cancer has evolved, with HER2-targeted therapies demonstrating improved survival for patients with early-stage or metastatic disease. “The rationale for this guideline is that several new agents have been approved by the US Food and Drug Administration [FDA] for the treatment of metastatic HER2-positive breast cancer since the approval of trastuzumab,” noted Sharon H. Giordano, MD, M.D. Anderson Cancer Center, Houston, and colleagues.
Since the approval of trastuzumab in 1998, lapatinib (Tykerb), pertuzumab (Perjeta), and ado-trastuzumab emtansine (T-DM1; Kadcyla) have also received FDA approval.
ASCO convened a panel of experts to conduct a systematic literature review from 2009 to 2012 that addressed overall survival (OS), progression-free survival (PFS), and adverse events. A total of 16 trials met the inclusion criteria. Among the studies considered were the CLEOPATRA trial, an international, multicenter, randomized, double-blind, placebo-controlled, phase 3 trial comparing the combination of pertuzumab, trastuzumab, and docetaxel with the combination of trastuzumab and docetaxel as first-line treatment for patients with previously untreated HER2-positive metastatic breast cancer. They also assessed the phase 3 EMILIA trial, an open-label study comparing T-DM1 versus capecitabine plus lapatinib in patients with HER2-positive locally advanced or metastatic breast cancer.
The CLEOPATRA trial found OS and PFS benefits with docetaxel, trastuzumab, and pertuzumab in first-line treatment. The EMILIA trial found survival and PFS benefits for T-DM1 in second-line treatment and PFS benefits in third-line treatment.
Three trials also evaluated endocrine therapy for patients with HER2-positive advanced breast cancer. “Approximately half of all HER2-positive breast cancers are also hormone receptor positive,” noted the researchers. “The dependency of HER2-positive, hormone receptor–positive tumors on estrogen signaling is only partially understood.” The guideline therefore addressed the use of endocrine therapy in this subset of patients.
