Neelima Denduluri, MD
Patients with early-stage breast cancer facing a high risk of recurrence would benefit from the expanded use of adjuvant therapy, according to updated guidelines from the American Society of Clinical Oncology (ASCO). The recommendations cover clinical scenarios for patients with residual invasive HER2-negative disease after surgery and those with HER2-positive tumors who are candidates for additional targeted therapy (Table
The ASCO guidelines are adapted from Cancer Care Ontario recommendations for selecting optimal treatment regimens. Neelima Denduluri, MD, co-chair of the ASCO expert panel that wrote the guidelines, said in a podcast that the focused update comes in response to seminal results from the CREATE-X (UMIN000000843), ExteNET (NCT00878709), and APHINITY (NCT01358877) trials.2
ASCO issued the update after reviewing data “that has the potential to impact practice of clinical medicine.”
For patients with HER2-positive tumors, the guideline covers 2 clinical situations. “The update focuses on women with early breast cancer who have HER2-positive disease and have had all their tumor removed, and it focuses on what is the appropriate adjuvant therapy for women with HER2-positive breast cancer and early breast cancer,” said Denduluri, a medical oncologist with Virginia Cancer Specialists in Arlington.
“The third topic that this guideline update covers is in women with HER2-negative disease who we’ve chosen to give preoperative therapy and, at the time of surgery, they have a residual cancer burden. For those patients, in the past, we never had a standard therapy that we can discuss with them.”
Specifically, the update delves into these questions:
• Should patients with early-stage HER2-negative breast cancer with residual invasive disease at surgery receive adjuvant capecitabine (Xeloda) following completion of standard preoperative anthracycline- and taxane-based combination chemotherapy in patients?
• Should patients with early-stage HER2-positive breast cancer receive 1 year of adjuvant pertuzumab (Perjeta) in addition to trastuzumab (Herceptin)-based combination chemotherapy?
• Should patients with early-stage HER2-positive breast cancer receive extended adjuvant therapy with neratinib (Nerlynx) following combination chemotherapy and trastuzumab-based adjuvant therapy?
Capecitabine in HER2-Negative Disease
ASCO offered a moderate recommendation based on “intermediate” evidence in favor of adding adjuvant capecitabine following standard anthracycline- and taxane-based preoperative therapy for patients with early-stage HER2-negative breast cancer who have pathologic invasive residual disease at surgery (Figure
The recommendation is based on data from CREATE-X (N = 910). That randomized phase III trial evaluated the effect of 6 to 8 cycles of adjuvant capecitabine on disease-free survival (DFS) and overall survival (OS) in patients with stage I-IIIB HER2-negative disease who received neoadjuvant anthracycline, taxane, or combined anthracycline and taxane therapy with curative intent.
The trial was stopped early after meeting its primary endpoint for DFS. At a median follow-up of 3.6 years, the 5-year DFS rate was 74.1% for the capecitabine arm versus 67.6% for the control arm (HR, 0.70; 95% CI, 0.53-0.92; P
= .01). OS was also superior in the capecitabine arm (89.2% vs 83.6%; HR, 0.59; 95% CI, 0.39-0.90; P
= .01). Patients with triple-negative breast cancer and hormone receptor–positive breast cancer also benefitted from capecitabine treatment.
The update also addresses women with HER2-negative disease who have residual cancer burden at the time of surgery despite receiving preoperative therapy. Those women are at increased risk for relapse, but data from the CREATE-X trial suggest that these patients derive benefit from the addition of adjuvant capecitabine. The panel concluded that adjuvant capecitabine was likely to benefit patients with triple-negative disease as well.
Table. Updated ASCO Recommendations for Early-Stage Breast Cancer
In patients with triple-negative disease, DFS was 69.8% versus 56.1% (HR, 0.58, 95% CI, 0.39 to 0.87) in favor of the capecitabine arm. Capecitabine was associated with superior OS (78.8% vs 70.3%; HR, 0.52; 95% CI, 0.30-0.90) and conferred a survival advantage to patients with hormone receptor–positive breast cancer.