Carey K. Anders, MD, medical oncologist, medical director, Brain and Spine Metastases Program, Duke Cancer Center, Duke Health, discusses navigating the treatment landscape of metastatic triple-negative breast cancer (mTNBC).

Several factors should be considered when selecting treatment for a patient with mTNBC, Anders explains. These factors include the patient’s symptom burden, their baseline health status, and the tolerability of the therapy. Additionally, patient preference is an important factor to consider during the decision-making process, Anders adds. 

Moreover, from a biological perspective, it is important understand whether the patient is PD-L1 positive or negative. Patients with PD-L1–positive disease are eligible to receive up-front chemoimmunotherapy, whereas patients with PD-L1–negative disease receive single-agent chemotherapy in the frontline setting, Anders explains. 

In the second- and later-line settings, the antibody-drug conjugate sacituzumab govitecan-hziy (Trodelvy) or clinical trials may be considered, Anders concludes.

Videos

Carey K. Anders, MD, discusses navigating the treatment landscape of metastatic triple-negative breast cancer. 


Dr. Anders on Navigating the Treatment Landscape of Metastatic TNBC 

Carey Anders, MD, medical director, Brain and Spine Metastasis Program, and medical oncologist, Duke Cancer Institute, discusses sequencing strategies in the setting of HER2-positive breast cancer with brain metastases.

Currently, when a patient is diagnosed with brain metastases, a radiation therapist and neurosurgeon are brought into the decision-making process, says Anders. If the patient has a mass-occupying solitary lesion that’s causing significant symptoms, or has an unknown histology, they’ll typically undergo a neurosurgical resection followed by radiosurgery. If the patient doesn't undergo neurosurgery, radiation therapy is administered as local therapy to the metastatic lesion, explains Anders.

The systemic therapy that is sequenced after local therapy has to be selected very carefully. In a patient with HER2-positive disease who has been treated with local therapy and doesn’t have progression in the extracranial compartment, the same systemic therapy is continued in accordance with the ASCO guidelines. In a patient with concurrent progressive extracranial disease, the systemic therapy is often switched in an attempt to treat the intercranial, but also the extracranial, disease progression, concludes Anders.

Dr. Anders on Sequencing Strategies in the Setting of HER2+ Brain Metastases

Carey Anders, MD, medical director, Brain and Spine Metastasis Program, Duke Cancer Institute, discusses the use of neratinib (Nerlynx) and capecitabine in patients with HER2-positive breast cancer that has metastasized to the brain.

At the 2019 ASCO Annual Meeting, results from the phase III NALA trial were presented. In the trial, patients with or without brain metastases were randomized to receive the combination of the irreversible pan-HER TKI neratinib plus capecitabine or the reversible TKI, lapatinib (Tykerb) plus capecitabine. Results demonstrated an improvement in progression-free survival with the neratinib combination in all-comers. Notably, in patients with brain metastases, the time to intervention was delayed with neratinib.

Based on these results, and in the absence of a contraindication, patients with HER2-positive brain metastases should receive the combination of neratinib and capecitabine as opposed to the combination of lapatinib and capecitabine, says Anders. If patients start on the combination of neratinib and capecitabine, they should also receive antidiarrheal prophylaxis, particularly within the first 2 cycles of treatment with neratinib, she concludes.

Carey Anders, MD, director, Brain and Spine Metastasis Program, Duke Cancer Institute, discusses the use of neratinib (Nerlynx) and capecitabine in patients with HER2-positive breast cancer that has metastasized to the brain.

Dr. Anders Discusses the Use of Neratinib/Capecitabine for HER2-Positive Brain Metastases

Carey Anders, MD, director, Brain and Spine Metastasis Program, Duke Cancer Institute, discussed the use of abemaciclib (Verzenio), a selective CDK4/6 inhibitor, in patients with hormone receptor—positive, HER2-negative metastatic brain cancer with brain metastases.

In the study, 52 patients were evaluated and had a median of 4 prior systemic therapies. Of the group, 75% had prior chemotherapies and 71% had endocrine therapy in the metastatic setting. Moreover, 50% had whole brain radiotherapy, 39% stereotactic radiosurgery, and 8% had surgical resection of their brain metastases. Despite most patients being heavily pretreated, 40% of the lesions were unirradiated, allowing researchers to see the full impact of the drug. Patients received 200 mg of abemaciclib orally twice daily.

Three patients had a confirmed intracranial response (5.8%), which did not meet the 11% stipulated protocol. However, the intracranial clinical benefit was 25%. Additionally, 38% of patients showed a decrease in the sum of their intracranial lesions. Median progression-free survival was 4.4 months (95% CI, 2.6-5.5).

Further abemaciclib studies are necessary to assess its potential as monotherapy and combination strategies to better control brain metastases in multiple diseases.

Carey Anders, MD, director, Brain and Spine Metastasis Program, Duke Cancer Institute, discussed the use of abemaciclib, a selective CDK4/6 inhibitor, in patients with hormone receptor–positive, HER2-negative metastatic brain cancer with brain metastases.

Dr. Anders on Abemaciclib in HR+ Breast Cancer With Brain Metastases

Carey Anders, MD, assistant professor for the Department of Medicine, Division of Hematology and Oncology, at UNC-Chapel Hill, UNC Linebarger Comprehensive Cancer Center, discusses systemic agents available and in development for patients with breast cancer who also have brain metastases.

In terms of systemic therapy, there are methods of treating patients with triple-negative breast cancer, estrogen-receptor—positive disease, and HER2-positive disease. However, the depth of work has really involved in the HER2 subset, she explains.

Lapatinib (Tykerb) is know as the most "tried-and-true" method of treating patients with brain metastases and has been most extensively studied in HER2-positive disease. Next-generation compounds are also being explored, she adds, including ONT-380 and MM-302, which is a HER2-targeted liposomal doxorubicin. In particular, MM-302—an antibody-drug conjugate composed of a HER2-targeted antibody linked to liposomal doxorubicin&mdash;is being investigated in combination with trastuzumab in the phase II HERMIONE trial.

Patients are being randomized to MM-302 versus chemotherapy plus trastuzumab in patients with anthracycline-naïve, locally advanced, HER2-positive breast cancer who were previously treated with pertuzumab (Perjeta) and T-DM1 (ado-trastuzumab emtansine; Kadcyla).

Additionally, there are derivatives of irinotecan either as a prodrug or metabolite packed into liposomes.

Carey Anders, MD, assistant professor for the Department of Medicine, Division of Hematology and Oncology, at UNC-Chapel Hill, UNC Linebarger Comprehensive Cancer Center,  discusses systemic agents available and in development for patients with breast cancer who also have brain metastases. 

Dr. Anders on Systemic Agents for Patients With Breast Cancer and Brain Mets

Carey Anders, MD, assistant professor for the Department of Medicine, Division of Hematology and Oncology, at UNC-Chapel Hill, UNC Linebarger Comprehensive Cancer Center, discusses why brain metastases is such a prominent issue in patients with breast cancer in an interview during the 2016 

 State of the Science Summit on Metastatic Breast Cancer.

Brain metastases in breast cancer are becoming more common, Anders says. While systemic therapies have improved, the brain remains a sanctuary site for cancer cells to grow.

Researchers are still at the very cusp of understanding the biology of why this occurs, though there is evidence that suggest it is a subtype dependent. Patients with HER2, triple-negative, or basal-like disease are more likely to develop brain metastases, she adds.

Carey Anders, MD, assistant professor for the Department of Medicine, Division of Hematology and Oncology, at UNC-Chapel Hill, UNC Linebarger Comprehensive Cancer Center, discusses why brain metastases is such a prominent issue in patients with breast cancer in an interview during the 2016 OncLive State of the Science Summit on Metastatic Breast Cancer.

Carey Anders, MD

Articles

Dr. Anders on Navigating the Treatment Landscape of Metastatic TNBC

Dr. Anders on Sequencing Strategies in the Setting of HER2+ Brain Metastases

Dr. Anders Discusses the Use of Neratinib/Capecitabine for HER2-Positive Brain Metastases

Dr. Anders on Abemaciclib in HR+ Breast Cancer With Brain Metastases

Dr. Anders on Systemic Agents for Patients With Breast Cancer and Brain Mets

Dr. Anders on Challenge of Brain Mets in Breast Cancer