Sara A. Hurvitz, MD, director of the Breast Oncology Program at the University of California, Los Angeles, Jonsson Comprehensive Cancer Center, advises how to navigate therapy for patients with HER2-positive breast cancer.

The field of HER2-positive breast cancer has undergone immense change over the last few years. In July 2017, the FDA approved neratinib (Nerlynx) for the extended adjuvant treatment of patients with early stage, HER2-positive breast cancer following postoperative trastuzumab (Herceptin). Five months later, the FDA approved pertuzumab (Perjeta) in combination with trastuzumab and chemotherapy as an adjuvant treatment for patients with HER2-positive early breast cancer at high risk for recurrence.

Hurvitz says that with all these new agents, navigating through the options has become tricky. Neratinib is associated with significant gastrointestinal toxicity, particularly diarrhea. Hurvitz says that patients need to be premedicated with antidiarrheals and carefully educated on how to get in touch with their doctor. Pertuzumab also adds some toxicity, particularly an increase in diarrhea and poses a potential for febrile neutropenia. Patients on either of these medications should be monitored closely, Hurvitz advises.

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Sara A. Hurvitz, MD, director of the Breast Oncology Program at the University of California, Los Angeles, Jonsson Comprehensive Cancer Center, advises how to navigate therapy for patients with HER2-positive breast cancer.
 

Dr. Hurvitz on How to Navigate HER2-Targeted Therapy in Breast Cancer

Sara A. Hurvitz, MD, director of the Breast Oncology Program, medical director of the Clinical Research Unit, University of California, Los Angeles Jonsson Comprehensive Cancer Center, discusses the impact of biosimilars in the treatment of patients with breast cancer.

This is a very important class of drugs, says Hurvitz, and the implementation of biosimilars will globally give patients access to life-saving therapy. The approval of a trastuzumab (Herceptin) biosimilar is especially important because this drug isn’t typically available outside the United States. The cost of medicine in general is an issue that patients and physicians contend with, especially in the United States, where drugs are more expensive than anywhere else. Biosimilars could serve as an effective alternative.

Hurvitz adds that it is important for patients and clinicians to be educated on biosimilars. These are different from generic agents in that superiority is not the goal—similarity is.

Dr. Hurvitz on the Impact of Biosimilars

Sara A. Hurvitz, MD, director of the Breast Oncology Program at the University of California, Los Angeles, Jonsson Comprehensive Cancer Center, discusses the clinical use of biosimilars in oncology.

As of 2018, the only biosimilar that is being used in clinical practice in the US is the filgrastim (Neupogen) biosimilar. Hurvitz says that she gives her patients the biosimilar of filgrastim, as it is a more affordable version, and it has met the biosimilarity criteria required by the FDA.

Biosimilars for trastuzumab (Herceptin) and bevacizumab (Avastin) have been FDA approved, but the originator drugs are not yet off patent, so they are not available in the US for clinical use. Moreover, there is pending litigation regarding the patents, so it may be a few years before these biosimilars are used in the US as a treatment for cancer, Hurvitz concludes.

Sara A. Hurvitz, MD, director of the Breast Oncology Program at the University of California, Los Angeles, Jonsson Comprehensive Cancer Center, discusses the clinical use of biosimilars in oncology.
 

Dr. Hurvitz on the Clinical Use of Biosimilars in Oncology

Sara A. Hurvitz, MD, director of the Breast Oncology Program at the University of California, Los Angeles, Jonsson Comprehensive Cancer Center, discusses de-escalation in HER2-positive breast cancer.

It is difficult to distinguish which patients should receive traditional therapy from those who would benefit from a de-escalation of therapy, says Hurvitz. Hurvitz recommends that a 32-year-old patient with a very high-grade 1.2-cm tumor and lymphovascular invasion that is HER2-positive and estrogen receptor- and progesterone receptor-negative should undergo a more traditional approach supported by phase III evidence.

On the other hand, de-escalation may be a better option for a patient with HER2-positive breast cancer with hormone receptor co-expression in the tumor. Low- and intermediate-grade tumors, and lack of lymphovascular invasion are also indicators that de-escalation may be a safe route, but Hurvitz warns that this isn’t an exact science. Biomarkers are being looked to in clinical trials of de-escalation to better select patients.

Dr. Hurvitz Discusses De-Escalation in HER2+ Breast Cancer

Sara A. Hurvitz, MD, director of the Breast Oncology Program at the University of California, Los Angeles, Jonsson Comprehensive Cancer Center, discusses novel agents that are emerging in the HER2-positive breast cancer space. Hurvitz shared this insight in an interview with 

 during the 35th Annual Miami Breast Cancer Conference.

One of the agents that Hurvitz is looking forward to seeing more data of is tucatinib, previously known as ONT-380. This is a HER2 selective tyrosine kinase inhibitor with evidence that it crosses the blood-brain barrier and, therefore, has efficacy against patients with CNS metastases. Tucatinib has been granted orphan drug status based on phase I activity in CNS tumors that are HER2-positive. Tucatinib is being explored in the HER2CLIMB trial, a large phase II study of tucatinib plus trastuzumab (Herceptin) and capecitabine versus trastuzumab and capecitabine alone. This could potentially be an active drug for patients with or without progressive CNS metastases that are HER2-positive.

A second novel agent is an investigational antibody-drug conjugate DS-8201. This is showing promising activity in early-phase clinical trials, where it demonstrated objective response rates of more than 60% in patients with heavily pretreated metastatic HER2-positive breast cancer. DS-8201 received an FDA breakthrough therapy designation for the treatment of patients with HER2-positive, locally advanced, or metastatic breast cancer who have been treated with trastuzumab and pertuzumab (Perjeta) and have disease progression after ado-trastuzumab emtansine (T-DM1; Kadcyla) in August 2017.

View more from the 2018 Miami Breast Cancer Conference

Sara A. Hurvitz, MD, director of the Breast Oncology Program at the University of California, Los Angeles, Jonsson Comprehensive Cancer Center, discusses novel agents that are emerging in the HER2-positive breast cancer space. Hurvitz shared this insight in an interview with OncLive during the 35th Annual Miami Breast Cancer Conference.

Dr. Hurvitz on Novel Emerging Agents in HER2+ Breast Cancer

Sara A. Hurvitz, MD, medical oncologist, associate professor of Medicine, medical director, Jonsson Comprehensive Cancer Center Clinical Research Unit, UCLA, discusses the findings of the neoMONARCH trial, a neoadjuvant regimen combining the CDK4/6 inhibitor abemaciclib with anastrozole, which induced a response rate of 54.7% in patients with hormone receptor—positive, HER2-negative early-stage breast cancer.

View more from the 2016 San Antonio Breast Cancer Symposium

​Sara A. Hurvitz, MD, medical oncologist, associate professor of Medicine, medical director, Jonsson Comprehensive Cancer Center Clinical Research Unit, UCLA, discusses the findings of the neoMONARCH trial, a neoadjuvant regimen combining the CDK4/6 inhibitor abemaciclib with anastrozole, which induced a response rate of 54.7% in patients with hormone receptor–positive, HER2-negative early-stage breast cancer.

Sara A. Hurvitz, MD

Articles

Dr. Hurvitz on How to Navigate HER2-Targeted Therapy in Breast Cancer

Dr. Hurvitz on the Impact of Biosimilars

Dr. Hurvitz on the Clinical Use of Biosimilars in Oncology

Dr. Hurvitz Discusses De-Escalation in HER2+ Breast Cancer

Dr. Hurvitz on Novel Emerging Agents in HER2+ Breast Cancer

Dr. Hurvitz on neoMONARCH Trial for HR+ Breast Cancer