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Understanding the Clinical and Economic Burden of Metastatic HER2+ Breast Cancer

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Understanding the Clinical and Economic Burden of Metastatic HER2+ Breast Cancer Headline CONVERSATION WITH AN EXPERT Understanding the Clinical and Economic Burden of Metastatic HER2+ Breast Cancer AUGUST 2020 Disease burden diagnosis, total monthly costs were $13,000 Network (NCCN) guidelines recommend the Despite advances in treatment for breast to $34,000 higher for patients with HER2+ following as preferred treatments for recurrent cancer, 20% to 30% of patients experience re- metastatic disease compared with those with- or stage IV HER2+ mBC: pertuzumab plus lapse with distant metastatic disease. Human out metastatic disease. Costs were primarily trastuzumab and docetaxel (category 1) and epidermal growth factor receptor 2 (HER2)- related to outpatient visits ($195,162) and pertuzumab plus trastuzumab and paclitaxel positive disease is an independent risk factor HER2-targeted drugs ($177,489).13 One-year (category 2A). Other recommended therapies for relapse and has been associated with costs for patients with HER2+ mBC with brain in this setting include:21 increased risk of disease spread to specific metastases are 2.21 times higher compared sites.1 The estimated annual U.S. incidence of with patients without brain metastases.14 • Tucatinib plus trastuzumab and capecitabine HER2+ metastatic breast cancer (mBC) is just Patients with progressing brain metastases (category 1) under 9,000,2 and up to 14% of patients with have historically been excluded from clinical breast cancer have HER2+ disease,3 which trials because of their poor functional status, • Ado-trastuzumab emtansine (T-DM1; category tends to be more aggressive and more likely to shortened life expectancy, and increased risk 2A) recur than HER2-negative disease.1,4 of toxicity. Thus, there is an incomplete under- HER2+ disease also impacts survival, as standing of the natural history and manage- • Fam-trastuzumab deruxtecan-nxki (category 2A) the five-year survival rate for HER2+ mBC is ment of brain metastases in the real world and only about 28%.2,4 Deaths related to breast an unmet treatment need.4,15 • Trastuzumab plus paclitaxel and carboplatin cancer are often secondary to the impact of (category 2A) distant metastases, and the most common Treatment considerations sites of HER2+ mBC-related metastases are in Within the past year, the U.S. Food and Drug • Trastuzumab plus paclitaxel with or without the brain, bone, lung, and liver.5,6 Administration (FDA) approved three therapies carboplatin (category 2A) for HER2+ mBC. In December 2019, fam-tras- Impact of brain metastases tuzumab deruxtecan-nxki was approved for • Trastuzumab plus docetaxel (category 2A) Brain metastases occur at an increased rate patients with unresectable or metastatic in patients with HER2+ mBC; throughout the HER2+ breast cancer who have received two • Trastuzumab plus vinorelbine (category 2A) course of HER2+ mBC disease, up to 50% of or more prior anti-HER2-based regimens in the patients will develop brain metastases.6-9 Brain metastatic setting,16 based on results of the • Trastuzumab plus capecitabine (category 2A) metastases are associated with poor outcomes DESTINY-Breast01 clinical trial.17 In February and reduced quality of life, including shortened 2020, the FDA approved neratinib in combi- • Lapatinib plus capecitabine (category 2A) survival, limitations in activity, and cognitive nation with capecitabine for adult patients impairment.4,6 with advanced or metastatic HER2+ breast • Trastuzumab plus lapatinib without cytotoxic Brain metastases are difficult to treat be- cancer who have received two or more prior therapy (category 2A) cause many targeted therapies and cytotoxic anti-HER2-based regimens in the metastatic chemotherapies do not easily cross the intact setting, based on the results of the NALA • Trastuzumab plus other agents (category 2A) blood-brain barrier, thus offering a sanctuary clinical trial.18 In April 2020, the FDA approved for central nervous system (CNS) metastases tucatinib in combination with trastuzumab • Neratinib plus capecitabine (category 2A) and allowing them to develop independently and capecitabine for adults with advanced of extracranial disease control.10,11 Among those unresectable or metastatic HER2+ breast Of the NCCN-recommended treatments, tuca- with brain metastases, patients are also more cancer, including patients with brain metas- tinib is one of a few breast cancer studies that likely to die from progression in the CNS com- tases, who have received one or more prior included patients with active brain metasta- pared with extracranial disease progression.11,12 anti-HER2-based regimens in the metastatic ses.20 Tucatinib is also the only FDA-approved In addition, brain metastases are associat- setting,19 based on results of the HER2CLIMB drug that includes brain metastases in its ed with a high economic burden. A retro- clinical trial.20 indication.22 Clinical trials assessing fam-tras- spective cohort study found that, following The National Comprehensive Cancer tuzumab deruxtecan-nxki and neratinib also Sponsored Content by Seattle Genetics conversationName of New Piece with an expert included patients with brain metastases; barrier, allowing for a sanctuary site. Preclinical prospectively looking at this to determine if we however, these represented only a small por- studies have shown that HER2 can enhance could diagnose brain metastasis earlier in an tion of the trial cohort and were restricted to recurrence in the CNS. asymptomatic state, and perhaps decrease the stable brain metastases only, not progressing Another challenge in the stage IV setting need for therapy that might later cause side ones.23,24 is that patients’ tumors acquire resistance to effects; this could not only improve patient The American Society of Clinical Oncology their current therapy. Women can go many outcomes, but also quality of life. (ASCO) practice guidelines recommend surgery months, sometimes years, on the same thera- with postoperative radiation, whole-brain py, and ultimately, the tumors start to acquire Q: What are the key differences caused by radiotherapy, and stereotactic radiosurgery resistance mechanisms—then we come in with brain metastases for your patients? depending on metastasis size, resectability, the next line of systemic therapy to circumvent A: Many patients with brain metastasis present and symptoms for HER2+ mBC with brain those resistance mechanisms. with symptoms, and those symptoms can metastases. For patients without a known The therapies come with toxicity, and each be life-altering—difficulty with memory and history or symptoms of brain metastases, the has their own unique toxicity profile—anything function, upper or lower extremity control, ASCO guidelines do not recommend magnetic from mucositis and diarrhea to myelosuppres- and disease in the posterior cranial fossa resonance imaging (MRI) to screen for brain sion and alopecia. In addition to managing can also present with balance difficulties and metastases.25 the disease itself and resistance mechanisms vertigo. Many patients will have headaches. Carey K. Anders, MD, medical director that can emerge, we need to help the patient The symptom burden is problematic in terms of of the Duke Brain and Spine Metastases through their experience, so they are able to quality of life. Program, a member enjoy their time of stability and not be fraught Many of the initial HER2-directed or of the neuro-oncology with side effects. antibody-based therapies (larger, bulkier (primary) and breast monoclonal antibodies) inherently do not cross cancer (secondary) Q: How common are brain metastases in an intact blood-brain barrier. You can envision programs within the patients with HER2+ mBC? How common that larger molecules might be able to traverse Duke Cancer Institute, are asymptomatic patients, and how do you a region within the blood-brain barrier that is and a Translating Duke identify them? disrupted by tumor, but globally, antibodies Health Scholar, dis- A: Unfortunately, it’s very common. In the have a harder time accessing the CNS. When cussed the treatment advanced setting, we see that about one- we’re thinking about a treatment trajectory Carey K. Anders, MD landscape for patients third of patients who have advanced HER2+ for patients with advanced disease and brain with HER2+ mBC and brain metastasis and breast cancer will eventually develop brain metastasis, we’re trying to control extracranial how the new treatment options may fit into the metastases during the course of their disease. disease in the liver, lung, or bone, but we’re paradigm. The number of patients who present with CNS also trying to think about therapies that will metastasis as their first site of disease is lower, get into the CNS, such as the smaller tyrosine Q: What are the key unmet needs for the approximately 10% to 15%. If you look across kinase inhibitors (TKIs) that may have better HER2+ mBC population that you see in your all patients with HER2+ breast cancer, across access to the CNS. practice? all stages, the number of patients who will A: My practice in breast oncology spans stages develop CNS metastasis is definitely less than Q: What is your opinion on the ASCO guide- I-IV, including patients with brain metastasis. 10%. But for those who are already at stage IV, lines about maintaining systemic therapy in I also have a special interest in young women the rate can be as high as one in three.8,26 the case of isolated brain progression? diagnosed with breast cancer and those who Many times, these women will present A: The ASCO guidelines25 for the manage- have CNS recurrence. With the latter as an with a spectrum of neurologic conditions. We ment of patients with HER2+ breast cancer interest, a large majority of my patients are also see the diagnosis of brain metastasis in with brain metastasis essentially say that if stage IV. I think we have fantastic therapies patients who were asymptomatic, and many a patient is eligible for a local therapy to the that were not available when I was in training, times that occurs when we’re screening for a brain, either neurosurgical resection followed particularly in the neoadjuvant and adjuvant clinical trial.
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