Chau T. Dang, MD, the Regional Care Network Medical Site Director at Memorial Sloan Kettering Westchester, discusses the safety profile of pertuzumab (Perjeta) plus trastuzumab (Herceptin) in patients with HER2-positive locally advanced, inflammatory, or early-stage breast cancer. 

The 5-year results from the final analysis of the phase 2 BERENICE trial (NCT02132949), which were presented during the 

, showed that in cohort A of the study, in which patients were treated with standard anthracycline-based chemotherapy followed by pertuzumab/trastuzumab and paclitaxel, incidence of New York Heart Association (NYHA) class III/IV heart failure was 1.5% in the neoadjuvant setting, Dang says.

Additionally, in cohort B, where patients received treatment with 5-fluorouracil/epirubicin/cyclophosphamide followed by docetaxel and pertuzumab/trastuzumab, no incidence of NYHA class III/IV heart failure was reported, Dang notes. 

The study followed patients through to the treatment-free follow-up period to report events after the neoadjuvant setting, Dang explains. For cohort A, no additional cardiac events were reported after the neoadjuvant phase, keeping the rate of NYHA class III/IV heart failure at 1.5%. In cohort B, 1 cardiac event was reported in the adjuvant setting, and 1 during the treatment-free follow-up period, which brought the NYHA class III/IV heart failure rate to 1%, Dang concludes. 

Videos

Chau T. Dang, MD, discusses the safety profile of pertuzumab plus trastuzumab in patients with HER2-positive locally advanced, inflammatory, or early-stage breast cancer. 


Dr. Dang on Cardiac Safety With Pertuzumab/Trastuzumab in Early-Stage HER2+ Breast Cancer

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.

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

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

Chau Dang, MD, medical oncologist, chief, West Harrison Medical Oncology Service, Memorial Sloan Kettering Cancer Center, discusses the potential of neratinib as part of a combination treatment for patients with HER2-positive breast cancer.

Currently, neratinib is being explored in combination with capecitabine versus lapatinib plus capecitabine in the phase III NALA study for HER2-positive patients who have received more than 2 treatments. This trial will allow researchers to determine whether this combination can be another treatment option for patients.

Dang explains that the incidence of grade 3 diarrhea associated with neratinib is an ongoing and significant issue; however, this toxicity can be managed through anti-diarrheal agents. Other small molecules are being developed in order to target these patients who also have brain metastases.

Chau Dang, MD, medical oncologist, chief, West Harrison Medical Oncology Service, Memorial Sloan Kettering Cancer Center, discusses the potential of neratinib as a combination treatment for patients with HER2-positive breast cancer.

Dr. Dang on Neratinib in Patients With HER2-Positive Breast Cancer

Chau Dang, MD, medical oncologist, chief, West Harrison Medical Oncology Service, Memorial Sloan Kettering Cancer Center, discusses the significance of MYL-1401O, a proposed biosimilar of trastuzumab, as a potential treatment for patients with HER2-positive metastatic breast cancer.

The study, which was originally reported by Hope Rugo, MD, at the 2016 ASCO Annual Meeting, looked at the activity of MYL-1401O with a taxane versus trastuzumab (Herceptin) with a taxane in the first-line setting of patients with HER2-positive metastatic breast cancer. This equivalency trial showed that the proposed biosimilar MYL-1401O was equivalent to trastuzumab in terms of efficacy and safety.

Because trastuzumab is not available worldwide due to cost factors, this biosimilar data could eventually lead to more affordable, global options for patients.

Chau Dang, MD

Articles

Dr. Dang on Cardiac Safety With Pertuzumab/Trastuzumab in Early-Stage HER2+ Breast Cancer

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

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

Dr. Dang on Neratinib in Patients With HER2-Positive Breast Cancer

Dr. Dang on the Significance of the MYL-1401O Biosimilar in HER2-Positive Metastatic Breast Cancer