Lisa A. Carey, MD, FASCO, The Richardson and Marilyn Jacobs Preyer Distinguished Professor in Breast Cancer Research, deputy director of clinical sciences, division chief, Hematology and Oncology, UNC Lineberger Comprehensive Cancer Center, discusses the clinical implications of the phase 3 FeDeriCa trial (NCT03493854) in HER2-positive breast cancer.

The FeDeriCa trial met its primary end point by showing that the subcutaneous formulation of the fixed-dose combination of trastuzumab (Herceptin) and pertuzumab (Perjeta) with hyaluronidase-zzxf (Phesgo)

provided noninferior cycle 7 pertuzumab serum Ctrough concentrations compared with intravenous (IV) trastuzumab plus pertuzumab as neoadjuvant and adjuvant treatment for patients with early-stage HER2-positive breast cancer. Additionally, the total pathologic complete response rates were comparable between regimens, says Carey. 

As such, the subcutaneous formulation of trastuzumab plus pertuzumab is a reasonable treatment option for patients in this setting, Carey says. Moreover, findings from the phase 2 PHranceSCa trial (NCT03674112) demonstrated that the majority of patients evaluated preferred the subcutaneous vs IV administration of trastuzumab plus pertuzumab. The subcutaneous formulation offers patients ease of administration with less time in an infusion center, concludes Carey. 

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Lisa A. Carey, MD, FASCO, discusses the clinical implications of the phase 3 FeDeriCa trial in HER2-positive breast cancer.  



Dr. Carey on the Clinical Implications of the FeDeriCa trial in HER2+ Breast Cancer 

Lisa Carey, MD, associate director, Clinical Research, UNC Lineberger Comprehensive Cancer Center, Richardson and Marilyn Jacobs Preyer Distinguished Professorship for Breast Cancer Research, UNC-Chapel Hill, discusses the ongoing progress with agents in development for the potential treatment of patients with HER2-positive breast cancer.

The paradigm for HER2-positive breast cancer has been an incredible trajectory over the last few years, Carey explains. Some of the more exciting agents that are in development, she adds, are the small molecule inhibitors, such as neratinib. Some of these drugs may be easier to combine with monoclonal-based therapy, or they may be better than them alone. However, combinations may be much more effective, she says. Future treatment approaches will look to understand who needs combinations versus monotherapy.  

One of the problems with HER2-directed therapies is their cost, Carey explains. However, some patients may do well with the biologically equivalent agent of trastuzumab (Herceptin). On the other hand, there are other patients who need dual therapy with multiple HER2-targeted drugs.

Previously, it may have been thought that pharmaceutical companies and drug developers would not spend time investigating in the area of HER2-positive breast cancer but, Carey explains, HER2 is an attractable target. Also, it is likely that, in the future, biomarkers will evolve past HER2 and incorporate other targets.

Dr. Carey on Ongoing Progress in HER2+ Breast Cancer

Lisa Carey, MD, associate director, Clinical Research, UNC Lineberger Comprehensive Cancer Center, Richardson and Marilyn Jacobs Preyer Distinguished Professorship for Breast Cancer Research, UNC-Chapel Hill, discusses how she has seen various agents impact quality of life (QOL) when used to treat patients with breast cancer.

An obvious example of taking toxicity into account is the adverse event of neuropathy, which is a common side effect associated with an adjuvant taxane therapy, Carey explains. While taxanes are among the most effective treatments for patients with metastatic triple-negative breast cancer in the first-line setting, it may not be a good idea to continue therapy with a taxane for a patient with a severe case of neuropathy.

For other patients, gastrointestinal toxicities may be particularly bothersome and may be a reason to switch treatments. However, there are other patients for whom adherence is difficult; therefore, intravenous therapy may be more convenient for them. From the standpoint of tolerability and preference, that may also be an important reason to individualize therapy, Carey adds.

Dr. Carey on QOL Changes Seen in Patients With Breast Cancer

Lisa Carey, MD, associate director, Clinical Research, UNC Lineberger Comprehensive Cancer Center, Richardson and Marilyn Jacobs Preyer Distinguished Professorship for Breast Cancer Research, UNC-Chapel Hill, discusses the possibility of administering immunotherapy as treatment for patients with HER2-positive breast cancer, in an interview during the 2016 OncLive State of the Science Summit on Metastatic Breast Cancer.

Immunotherapy is likely to be studied in all subtypes of breast cancer, Carey explains. Though researchers currently do not know how to select for this type of treatment, similar studies showing restrictions in the B-cell receptor that are suggestive of clonal expansion and an actual antigenic response are highest in triple-negative and HER2-enriched breast cancers.

There is a rationale for looking at immunotherapy in this patient population, Carey adds, and manipulating the microenvironment could have an impact across all tumors.

Lisa Carey, MD, associate director, Clinical Research, UNC Lineberger Comprehensive Cancer Center, Richardson and Marilyn Jacobs Preyer Distinguished Professorship for Breast Cancer Research, UNC-Chapel Hill, discusses the possibility of administering immunotherapy as treatment for patients with HER2-positive breast cancer.

Lisa Carey, MD

Articles

Dr. Carey on the Clinical Implications of the FeDeriCa trial in HER2+ Breast Cancer

Dr. Carey on Ongoing Progress in HER2+ Breast Cancer

Dr. Carey on QOL Changes Seen in Patients With Breast Cancer

Dr. Carey on Possibility of Immunotherapy in HER2+ Breast Cancer