Chau Dang, MD, medical oncologist, chief, West Harrison Medical Oncology Service, Memorial Sloan Kettering Cancer Center, discusses the evaluation of the efficacy of fam-trastuzumab deruxtecan-nxki (Enhertu; DS-8201) in HER2-positive metastatic breast cancer in the DESTINY-Breast01 trial.

Fam-trastuzumab deruxtecan-nxki is a potent antibody-drug conjugate with a payload at an 8:1 ratio from drug to antibody, explains Dang. This heavily pretreated patient population was found to have a response rate of about 60%. Additionally, the median progression-free survival was 16 months and the median overall survival has not been reached.

A small subgroup of patients with brain metastases participated in the trial and results are pending regarding the activity of fam-trastuzumab deruxtecan-nxki in this patient population, says Dang.

The most prominent adverse event is interstitial lung disease, which is currently being investigated in terms of monitoring and managing patients. Overall, patients with HER2-positive metastatic breast cancer should be receiving fam-trastuzumab deruxtecan-nxki in the third-line space, concludes Dang.

Videos

Chau Dang, MD, discusses the evaluation of the efficacy of fam-trastuzumab deruxtecan-nxki in HER2-positive metastatic breast cancer in the DESTINY-Breast01 trial.

Dr. Dang on the DESTINY-Breast01 Trial in HER2+ Metastatic Breast Cancer

Sara A. Hurvitz, MD, medical oncologist, medical director, Clinical Research Unit for University of California, Los Angeles Jonsson Comprehensive Cancer Center, discusses treatment options for patients with HER2-positive metastatic breast cancer.

HER2-positive breast cancer comprises 15% to 20% of all metastatic breast cancer but HER2-positive breast cancer is made of many different subtypes, explains Hurvitz. One of the most important features of HER2-positive breast cancer is whether the tumor has hormone co-expression, says Hurvitz. With a tumor that expresses both HER2 and hormone receptors, drugs that target the hormone and HER2 pathways can be used.

Additionally, studies are examining whether CDK4/6 inhibitors work well in this patient population, including the monarcHER study, which shows that adding abemaciclib (Verzenio) to trastuzumab (Herceptin) and fulvestrant improves outcomes for patients with metastatic hormone receptor—positive, HER2-positive breast cancer. In the future, patients with 

 mutations will also be examined and research will continue to investigate whether adding drugs, such as alpelisib (Piqray), to HER2-targeted therapy will improve outcomes for patients with HER2-positive breast cancer, concludes Hurvitz.

Sara A. Hurvitz, MD, discusses treatment options for patients with HER2-positive metastatic breast cancer.

Dr. Hurvitz on Therapeutics for HER2+ Metastatic Breast Cancer

Lowell L. Hart, MD, FACP, scientific director of clinical research at Florida Cancer Specialists & Research Institute, and associate professor of internal medicine at Wake Forest School of Medicine, discusses detection and treatment of interstitial lung disease for patients with HER2-positive breast cancer who received fam-trastuzumab deruxtecan-nxki (Enhertu; DS-8201).

The best way to detect interstitial lung disease early is to keep a high index of suspicion and closely monitor patients for unexplained cough, pulmonary symptoms, or shortness of breath upon exertion, explains Hart. If patients exhibit any of these symptoms, they should get imaging, such as a CT scan. If interstitial infiltrates are found and the patient does not have an infection, the interstitial lung disease is likely related to the drug, says Hart.

To treat drug-related interstitial lung disease, the patient must stop treatment and begin therapy with steroids, whether oral prednisone or intravenous steroids, according to Hart. If the patient requires hospitalization for interstitial lung disease, Hart recommends getting a pulmonary expert involved.

Lowell L. Hart, MD, FACP, discusses detection and treatment of interstitial lung disease for patients with HER2-positive breast cancer who received fam-trastuzumab deruxtecan-nxki.

Dr. Hart on Detecting and Treating Interstitial Lung Disease in HER2+ Breast Cancer

Hope S. Rugo, MD, a professor in the Department of Medicine, Hematology/Oncology, and director, Breast Oncology and Clinical Trials Education, University of California, San Francisco, Helen Diller Family Comprehensive Cancer Center, discusses the impact of margetuximab in patients with HER2-positive metastatic breast cancer who have an F allele versus V allele, according to findings of the phase III SOPHIA trial.

While examining the impact of the IgG Fc gamma receptor differences on the activity of margetuximab, it was observed that there are 2 variants with the CD16A Fc receptor: the F allele and the V allele, explains Rugo. Data have already shown that the addition of trastuzumab (Herceptin) to chemotherapy in patients who had the high-affinity allele benefited the most from trastuzumab; however, there was a decreasing benefit if patients had FV or FF, says Rugo.

Rugo hypothesized that patients who carried the F allele would have better responses to margetuximab. When looking at overall survival (OS) based on patients who had the F allele, FF or FE, there was a bigger difference in OS with an absolute difference of 4.3 months, which was not statistically significant with a P value of .08, according to Rugo.

Meanwhile, when looking at patients who are homozygous for V, patients randomized to margetuximab had much worse disease, including more brain metastases, visceral metastases, and other poor-prognostic features, concludes Rugo.

Hope S. Rugo, MD, discusses the impact of margetuximab in patients with HER2-positive metastatic breast cancer who have an F allele versus V allele.

Dr. Rugo on the Impact of Margetuximab Based on CD16A Fc Receptors in HER2+ Breast Cancer

Chau Dang, MD, medical oncologist, chief, West Harrison Medical Oncology Service, Memorial Sloan Kettering Cancer Center, discusses the APHINITY trial, which explored the use of pertuzumab (Perjeta) in combination with trastuzumab (Herceptin) plus chemotherapy in patients with high-risk HER2-positive breast cancer.

In this trial, pertuzumab, trastuzumab, and chemotherapy demonstrated a 0.9% absolute improvement in overall survival (OS) compared with trastuzumab and chemotherapy alone; the triplet regimen continued to reduce the risk of disease recurrence in patients with HER2-positive breast cancer. Longer follow-up at 6 years showed that the invasive disease-free survival benefit favored those who received the pertuzumab regimen. However, the OS improvement is not statistically significant, says Dang.

The triplet therapy suggests to be promising for patients with high burden disease, Dang says. The third interim OS analysis will occur in 2.5 years, and a definitive OS analysis will occur after 640 deaths out of 4804 patients.

Chau Dang, MD, discusses the APHINITY trial, which explored the use of pertuzumab (Perjeta) in combination with trastuzumab (Herceptin) plus chemotherapy in patients with HER2-positive breast cancer.
 

Dr. Dang on Long-Term Findings of the APHINITY Trial in HER2+ Breast Cancer

Lowell L. Hart, MD, FACP, scientific director of clinical research at Florida Cancer Specialists & Research Institute, and associate professor of internal medicine at Wake Forest School of Medicine, discusses personalized treatment approaches for patients with HER2-positive breast cancer.

Patients with HER2-positive breast cancer should be re-biopsied at the time of their first recurrence, Hart explains. Drugs including fam-trastuzumab deruxtecan-nxki (Enhertu; DS-8201), trastuzumab (Herceptin), antibody-drug conjugates, and TKIs such as lapatinib (Tykerb), as well as investigational TKIs, such as tucatinib. have shown efficacy in this patient population. Tucatinib demonstrated promising activity at the 2019 San Antonio Breast Cancer Symposium.

However, there is still a challenge in treating patients with HER2-positive breast cancer who have brain metastases. While certain systemic therapies may not cross the blood—brain barrier, some of the newer agents in the pipeline, such as tucatinib, are able to better penetrate the brain, Hart concludes.

Lowell L. Hart, MD, discusses personalized treatment approaches for patients with HER2-positive breast cancer.

Dr. Hart on Personalized Treatment Approach for Patients With HER2+ Breast Cancer

Madelaine Kuiper, MSN, RN, an advanced nurse practitioner who works with Ronald Reagan University of California, Los Angeles (UCLA) Medical Center and Santa Monica UCLA Medical Center, discusses the adverse event (AE) of interstitial lung disease (ILD), which can occur in patients with HER2-positive metastatic breast cancer who have received fam-trastuzumab deruxtecan-nxki (Enhertu; DS-8201). 

ILD is often presented through symptoms of a persistent dry cough and shortness of breath. Kuiper stresses that patients should inform their nurse practitioners and physicians of these symptoms immediately, so they can receive the proper care. Additionally, she advises other nurses to halt treatment and perform a CT scan of the chest. If ILD is detected, then steroids will be administered along with taking the patient off of therapy.

Kuiper stresses the importance of educating patients on the AEs of any type of systemic therapy they are put on. She raises the question on whether or not to reattempt treatment with fam-trastuzumab deruxtecan-nxki or to seek a new therapy for patients who experience ILD.

Madelaine Kuiper, MSN, RN, discusses the adverse event of interstitial lung disease, which can occur in patients with HER2-positive metastatic breast cancer who have received fam-trastuzumab deruxtecan-nxki.

Management and Treatment of Interstitial Lung Disease in Breast Cancer

Sarah A. Hurvitz, MD, medical oncologist, medical director, Clinical Research Unit for University of California, Los Angeles Jonsson Comprehensive Cancer Center, discusses the findings in the DESTINY-Breast01 trial of patients with HER2-positive metastatic breast cancer.

This was a single-arm, phase II study in which patients with HER2-positive metastatic breast cancer received fam-trastuzumab deruxtecan-nxki (Enhertu; DS-8201). Patients enrolled on the trial received a median of 6 prior lines of therapy.

Results showed that fam-trastuzumab deruxtecan-nxki led to an overall response rate of 60.3% and the median progressive-free survival was 16.4 months.

In reflecting on the future treatment of patients with HER2-positive metastatic breast cancer, Hurvitz stressed the importance of ongoing phase III randomized trials to regularize the future treatment of fam-trastuzumab deruxtecan-nxki.

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