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Director, Glenn Family Breast Center
Hematology and Medical Oncology
Winship Cancer Institute
Kevin Kalinsky, MD, MS: consultant, advisor, speaker: 4D Pharma, AstraZeneca, Cyclocel, Daichi Sankyo, Immunomedics, Lilly, Merck, Mersana, Novartis, Oncosec, Pfizer, Puma, Seattle Genetics.
In the past few years, there have been significant advances for patients with metastatic breast cancer with new agents that have improved survival for our patients. But what has been significantly impactful and exciting is that as these drugs move into the early‑stage breast cancer setting, they also are affecting patient outcomes in terms of preventing recurrence, improving breast cancer invasive disease‑free survival, and lowering the risk of a recurrence. I think we have seen this in particular in patients with early HER2‑negative breast cancer, and I will highlight 3 pivotal phase III clinical trials that led my colleagues and me to develop an Interactive Treatment Decision Support Tool to assist healthcare professionals in incorporating these data into clinical practice.
KEYNOTE-522: Neoadjuvant Pembrolizumab/Chemotherapy With Adjuvant Pembrolizumab in Triple-Negative Breast Cancer
In the phase III KEYNOTE‑522 trial, patients with early-stage, high-risk triple-negative breast cancer (TNBC) were enrolled. In the metastatic setting there are improved outcomes with pembrolizumab for patients who have PD‑L1–positive tumors. However, in the neoadjuvant setting, KEYNOTE-522 found that regardless of PD‑L1 status, for patients with a T2 or higher or node‑positive breast cancer, the addition of immunotherapy to chemotherapy followed by 1 year of adjuvant immunotherapy improved both pathologic complete response and event‑free survival. These data led to the approval of pembrolizumab for the treatment of patients with high-risk early-stage TNBC in combination with chemotherapy as neoadjuvant treatment, and then continued pembrolizumab as a single agent as adjuvant treatment after surgery. This has been a significant advance for this subtype of breast cancer, which really has needed additional therapy beyond chemotherapy.
OlympiA: Adjuvant Olaparib in BRCA-mutated, HER2-negative Breast Cancer
For patients with HER2-negative breast cancer who also have germline BRCA mutations, 1 year of adjuvant olaparib, a PARP inhibitor, decreases the risk of recurrence and increases overall survival of patients, as shown in the OlympiA phase III trial. Patients with a germline BRCA mutation and either hormone receptor–positive, HER2‑negative breast cancer or TNBC saw a benefit with adjuvant olaparib. Olaparib is approved for the adjuvant treatment of adult patients with deleterious or suspected deleterious germline BRCA mutation, HER2-negative, high-risk early breast cancer who have been treated with neoadjuvant or adjuvant chemotherapy.
monarchE: Adjuvant Abemaciclib in Hormone Receptor–Positive/HER2-Negative Breast Cancer
Finally, abemaciclib, a CDK4/6 inhibitor, is approved in combination with endocrine therapy for the adjuvant treatment of adult patients with hormone receptor–positive, HER2-negative, node-positive early breast cancer at high risk of recurrence and a Ki-67 score ≥20% as determined by an FDA-approved test. The approval was based on evidence from the phase III monarchE trial of abemaciclib plus endocrine therapy in patients with early-stage, high-risk, hormone receptor–positive breast cancer. Adjuvant abemaciclib plus endocrine therapy significantly improved invasive disease-free survival and distant relapse-free survival vs endocrine therapy alone.
Online Interactive Treatment Decision Support Tool
Given the rapid movement in the field and the complexity of treating our patients with high-risk, HER2‑negative early breast cancer, my colleagues and I have crafted an interactive treatment decision support tool focused on neoadjuvant and adjuvant therapy for this patient population (Figure 1). This tool has been assembled, evaluated, and designed by 5 experts who treat patients with breast cancer. As a user of the tool, you can enter key patient and disease characteristics to define a patient scenario.
Figure 1. Entering patient and disease characteristics into the tool.
After entering key patient and disease characteristics, you will select your intended treatment choice. After selecting your choice of therapy, the recommendations from all 5 experts for your individual set of characteristics will appear along with a link to additional information to consider (Figure 2).
Figure 2. Expert treatment recommendations.
When you have a patient in front of you, this tool hopefully will help inform the decision-making that needs to occur and the process you should consider in ultimately individualizing treatment for that person.
Questions to Answer
These data demonstrate that the drugs used in the metastatic setting also are important in the early‑stage setting, and as a result, we are left to figure out how to sequence these therapies for optimal outcomes. The advances are happening at such a pace that now we are also trying to determine which drugs might be given in combination—for instance, pembrolizumab and olaparib for a patient with BRCA-mutated TNBC. Additional biomarker work is needed to address which patients need these therapies and which do not.
We have a glimpse of where the field is going, also understanding that there are other drugs currently in the metastatic setting additionally being tested in the early stage setting to improve outcomes and decreasing the likelihood of recurrence for our patients who have been diagnosed with breast cancer.
What are your thoughts and questions on managing your patients with early‑stage, HER2‑negative breast cancer? Please answer the polling question and join the conversation by posting a comment in the discussion section below.