Journal of Oncology Navigation & Survivorship. 2018;9:198-199.
The updated guidelines from the National Comprehensive Cancer Network (NCCN) on the management of breast cancer (Version 1.2018) expand treatment options in HER2-positive disease to include extended adjuvant neratinib after completion of trastuzumab in patients with high risk of recurrence and recognize a third CDK4/6 inhibitor in hormone-sensitive breast cancer.
Sharon H. Giordano, MD, MPH, Professor in the Department of Breast Medical Oncology at the University of Texas MD Anderson Cancer Center, Houston, provided an update on the treatment of HER2-positive breast cancer, noting an “explosion of new therapies” in recent years that have had a tremendous impact on survival.
The CLEOPATRA study defined pertuzumab plus trastuzumab plus docetaxel as the standard of care for patients with HER2-positive metastatic breast cancer. The final overall survival (OS) analysis demonstrated an additional 15.7 months of survival by adding pertuzumab to trastuzumab and docetaxel. This triplet is now a preferred therapy for stage IV disease in the NCCN guidelines (category 1). “I think it’s also really remarkable that the median survival now is almost approaching 5 years for patients with metastatic HER2-positive breast cancer,” said Dr Giordano.
The standard second-line therapy in the HER2-positive metastatic setting is now trastuzumab emtansine based on an improvement in OS over capecitabine plus lapatinib in the EMILIA study.
In early-stage breast cancer, dual targeted therapy in the neoadjuvant setting has led to improvement in the rates of pathologic complete response. Dr Giordano cautioned that attempts to de-escalate therapy by removing chemotherapy and relying solely on trastuzumab and pertuzumab have not resulted in equivalent outcomes to maintaining chemotherapy.
In the early-stage adjuvant setting, an improvement in invasive disease-free survival (iDFS) with the addition of pertuzumab to chemotherapy and trastuzumab in the APHINITY trial led the FDA to grant regular approval to pertuzumab for the adjuvant treatment of HER2-positive breast cancer.
The ExteNET Adjuvant Trial demonstrated a modest improvement in iDFS with 1 year of neratinib following trastuzumab in the treatment of early-stage HER2-positive breast cancer, leading to FDA approval of neratinib for this indication. Patients in ExteNET who had hormone receptor (HR)-positive disease derived a slightly greater benefit than the HR-negative subset. The updated NCCN guidelines for systemic adjuvant treatment of HR-positive HER2-positive disease reflect this finding and now includes neratinib as an option following adjuvant trastuzumab in HR-positive patients with a perceived high risk of recurrence (such as stage II-III). The guidelines also state that the benefit or toxicities associated with extended neratinib in patients who have received pertuzumab is unknown.
In another de-escalation study known as APT, adjuvant paclitaxel and trastuzumab was associated with “excellent” outcomes (7-year DFS of 93.3%) in patients with T1 node-negative HER2-positive breast cancer, Dr Giordano noted.
Hormone-Sensitive Breast Cancer
William J. Gradishar, MD, Professor of Breast Oncology, Northwestern University, Chicago, IL, updated the status of treatment for patients with estrogen receptor (ER)-positive HER2-negative disease, saying that this is “the era of the CDK4/6 inhibitors.”
The most recent addition to the CDK4/6 inhibitor armamentarium is abemaciclib, which received FDA approval in combination with an aromatase inhibitor as initial endocrine-based therapy for postmenopausal women with HR-positive HER2-negative advanced or metastatic breast cancer. The data to support the use of CDK4/6 inhibitors for this indication have risen to the level of category 1, said Dr Gradishar.
In the first-line setting, adding a CDK4/6 inhibitor to endocrine therapy approximately doubled median progression-free survival (PFS) over endocrine therapy alone in 3 large clinical trials (PALOMA-2, MONALEESA-2, and MONARCH-3). “To a large extent, the results are fairly superimposable in the sense that they show a fairly striking improvement in PFS favoring the doublet over simply giving monotherapy,” he said. Every subgroup of patients examined appears to derive a PFS benefit with the addition of the CDK4/6 inhibitor. In MONARCH-3, the magnitude of benefit by adding a CDK4/6 inhibitor was greater in patients with poorer prognosis.