Adherence to prescribing restrictions for HER2-positive metastatic breast cancer in Australia: A national population-based observational study (2001-2016)

Background: Targeted cancer therapy is often complex, involving multiple agents and chemotherapeutic partners. In Australia, prescribing restrictions are put in place to reflect existing evidence of cost-effectiveness of these medicines. As therapeutic options continue to expand, these restrictions may not be perceived to align with best practice and it is not known if their use in the real-world clinic adheres to these restrictions. We examined the treatment of women receiving trastuzumab for HER2-positive metastatic breast cancer (HER2+MBC) to determine the extent to which treatment adhered to national prescribing restrictions. Patients and methods: Our population-based, retrospective cohort study used dispensing records for every Australian woman initiating publicly-subsidised trastuzumab for HER2+MBC between 2001±2013, followed through 2016. We used group-based trajectory models (GBTMs) to cluster patients, first on their patterns of trastuzumab exposure, and then on their patterns of lapatinib and chemotherapy exposure. We described the characteristics of patients within each cluster, and examined their treatments and combinations of treatments to determine restriction adherence. Results: Of 5,052 patients initiating trastuzumab, 1,795 (36%) received at least one non-adherent HER2-targeted treatment. The most common non-adherent treatments were trastuzumab combinations involving vinorelbine (24% of non-adherent treatments); capecitabine (24%); and anthracyclines (10%). Non-adherent lapatinib use was observed in 4% of patients. GBTM identified three trastuzumab exposure clusters, each containing three further subclusters. The largest proportions of non-adherent treatments were in sub-clusters with longer trastuzumab exposure and more non-taxane chemotherapy. Patients in these sub-clusters were younger than those in sub-clusters with less non-adherent treatment. Conclusions: Our study highlights that, even during the relatively simpler treatment era of our study period, a substantial amount of treatment did not adhere to prescribing restrictions. As more trials are conducted exploring pertuzumab and T-DM1 in combination with different chemotherapies and other HER2-targeted therapies, the regulation and funding of HER2-targeted treatment will become more challenging

Use and outcomes of targeted therapies in early and metastatic HER2-positive breast cancer in Australia: Protocol detailing observations in a whole of population cohort

Background: The management of human epidermal growth factor receptor 2 (HER2)-positive breast cancer (BC) has changed dramatically with the introduction and widespread use of HER2-targeted therapies. However, there is relatively limited real-world information on patterns of use, effectiveness and safety in whole of population cohorts. The research programme detailed in this protocol will generate evidence on the prescribing patterns, safety monitoring and outcomes of patients with BC treated with HER2- targeted therapies in Australia. Methods/design: Our ongoing research programme will involve a series of retrospective cohort studies that include every patient accessing Commonwealth-funded HER2-targeted therapies for the treatment of early BC and advanced BC in Australia. At the time of writing, our cohorts consist of 11 406 patients with early BC and 5631 with advanced BC who accessed trastuzumab and lapatinib between 2001 and 2014. Pertuzumab and trastuzumab emtansine were publicly funded for metastatic BC in 2015, and future data updates will include patients accessing these medicines. We will use dispensing claims for cancer and other medicines, medical service claims and demographics data for each patient accessing HER2- targeted therapies to undertake this research. Ethics and dissemination: Ethics approval has been granted by the Population Health Service Research Ethics Committee and data access approval has been granted by the Australian Department of Human Services (DHS) External Review Evaluation Committee. Our findings will be reported in peer-reviewed publications, conference presentations and policy forums. By providing detailed information on the use and outcomes associated with HER2-targeted therapies in a national cohort treated in routine clinical care, our research programme will better inform clinicians and patients about the real-world use of these treatments and will assist third-party payers to better understand the use and economic costs of these treatments

Metastatic breast cancer incidence, site and survival in Australia, 2001-2016: A population-based health record linkage study protocol

Introduction: Advances in systemic therapy for early and metastatic breast cancer (BC) over the last two decades have improved patients’ survival, but their impact on metastatic disease outcomes at a population level is not well described. The aim of this study is to investigate changes in the incidence, site and survival of metastatic disease for women with a first diagnosis of BC in 2001– 2002 vs 2006–2007. Methods and analysis: Population-based retrospective cohort study of women with first primary invasive BC registered in the New South Wales (NSW) Cancer Registry in 2001–2002 and 2006–2007. We will use linked records from NSW hospitals, dispensed medicines, outpatient services and death registrations to determine: women’s demographic and tumour characteristics; treatments received; time to first distant metastasis; site of first metastasis and survival. We will use the Kaplan-Meier method to estimate cumulative incidence of distant metastasis, distant recurrence-free interval and postmetastasis survival by extent of disease at initial diagnosis, site of metastasis and treatment-defined tumour receptor type (hormone receptor-positive, human epidermal growth factor receptor-2-positive, triple negative). We will use Cox proportional hazards regression to estimate the relative effects of prognostic factors, and we will compare systemic therapy patterns by area-of- residence and area-level socioeconomic status to examine equity of access to healthcare. Ethics and dissemination: Research ethics committee approval was granted by the Australian Institute of Health and Welfare (#EO2017/2/255), NSW Population and Health Services (#HREC/17/CIPHS/19) and University of Notre Dame Australia (#0 17 144S). We will disseminate research findings to oncology, BC consumer and epidemiology audiences through national and international conference presentations, lay summaries to BC consumer groups and publications in international peer-reviewed oncology and cancer epidemiology journals

Gaps in care and support for patients with advanced breast cancer: a report from the Advanced Breast Cancer Global Alliance

PURPOSE Although new therapeutic options continue to improve disease-related outcomes in advanced breast cancer (ABC), enhanced focus is needed to improve quality of life for patients currently living with ABC. METHODS In November 2019, a multidisciplinary workshop to explore patient perceptions of their information and support needs was held at the ABC Global Alliance Annual Meeting in Lisbon, Portugal. Ninety-two attendees from 27 countries participated in the workshop. RESULTS Several key unmet needs were identified and discussed in the workshop, including the following: (1) Significant patient knowledge gaps exist related to the diagnosis and management of ABC, and the availability of patient-focused information to support these gaps in knowledge remains limited. (2) The development of meaningful relationships between patients and health care professionals, and the role of patients in decision making, is often overlooked for patients with ABC. (3) Multidisciplinary care approaches are crucial for patients with ABC; however, these often lack effective coordination. (4) Access to clinical trials for ABC also remains limited. (5) Caregivers, friends, and family members do not receive sufficient guidance to support patients with ABC and manage their own well-being. CONCLUSION The variety of unmet needs explored in the workshop demonstrates that patients with ABC still face considerable challenges related to quality of care and support, which will not be resolved until tangible action is taken. Issues highlighted in the workshop should be prioritized by working groups to shape the development of community-based solutions. There is a need for the global community to act proactively to maximize awareness of these ongoing unmet needs and existing resources, while socializing and building new initiatives and resources that will help to close these gaps for patients

Patterns of care and outcomes among triple-negative early breast cancer patients in South Western Sydney

Background: Triple-negative breast cancer (TNBC) represents 12-24% of all breast cancer and carries a poor prognosis upon recurrence. Little is known of the treatment, or timing and frequency of recurrences outside of a clinical trial. Aim: We describe the patterns of care and outcomes of women with TNBC treated at two cancer centres in Sydney, NSW, Australia, to help oncologists talk to women with this subtype of breast cancer about their likely prognosis. Methods: We searched the electronic medical record for women with stages I–III TNBC diagnosed from 2006 to 2014. For each woman, we recorded demographics, tumour characteristics, treatment details, recurrences and survival using the Kaplan–Meier method. Results: We identified 137 women with a median age of 55 years (interquartile range (IQR) 44–63). The median tumour size was 25 mm (IQR 16–35). Most women had grade 3 (92%) and ductal carcinomas (89%), and 35% were node positive; 113 (82%) patients received (neo)adjuvant chemotherapy. The most prescribed regimens for node-negative tumours were: fluorouracil, epirubicin and cyclophosphamide (FEC) Ã 6 (23pts, 35%), and for node-positive tumours, FEC-Docetaxel (18pts, 40%). Adjuvant radiotherapy was delivered to 114 (83%) patients. After a median follow up of 40 months, 17 patients (12%) had a recurrence. All but one recurrence (94%) occurred within 3 years of diagnosis. Twelve women received palliative chemotherapy, and 14 women have died. The median survival from the time of recurrence was 18 months (IQR 5–26). Seven women (5%) had a documented BRCA1 mutation, and four women (3%) had a documented BRCA2 mutation. Conclusions: TNBC affects women at a relatively young age and tends to recur early. Survival following metastatic disease is short, and more effective therapies are needed

Scanxiety: a scoping review about scan-associated anxiety

Objectives To identify available literature on prevalence, severity and contributing factors of scan-associated anxiety (‘scanxiety’) and interventions to reduce it.Design Systematic scoping review.Data sources Ovid MEDLINE, Ovid EMBASE, Ovid PsycINFO, Ovid Cochrane Central Register of Controlled Trials, Scopus, EBSCO CINAHL and PubMed up to July 2020.Study selection Eligible studies recruited people having cancer-related non-invasive scans (including screening) and contained a quantitative assessment of scanxiety.Data extraction Demographics and scanxiety outcomes were recorded, and data were summarised by descriptive statistics.Results Of 26 693 citations, 57 studies were included across a range of scan types (mammogram: 26/57, 46%; positron-emission tomography: 14/57, 25%; CT: 14/57, 25%) and designs (observation: 47/57, 82%; intervention: 10/57, 18%). Eighty-one measurement tools were used to quantify prevalence and/or severity of scanxiety, including purpose-designed Likert scales (17/81, 21%); the State Trait Anxiety Inventory (14/81, 17%) and the Hospital Anxiety and Depression Scale (9/81, 11%). Scanxiety prevalence ranged from 0% to 64% (above prespecified thresholds) or from 13% to 83% (‘any’ anxiety, if no threshold). Mean severity scores appeared low in almost all measures that quantitatively measured scanxiety (54/62, 87%), regardless of whether anxiety thresholds were prespecified. Moderate to severe scanxiety occurred in 4%–28% of people in studies using descriptive measures. Nine of 20 studies assessing scanxiety prescan and postscan reported significant postscan reduction in scanxiety. Lower education, smoking, higher levels of pain, higher perceived risk of cancer and diagnostic scans (vs screening scans) consistently correlated with higher scanxiety severity but not age, gender, ethnicity or marital status. Interventions included relaxation, distraction, education and psychological support. Six of 10 interventions showed a reduction in scanxiety.Conclusions Prevalence and severity of scanxiety varied widely likely due to heterogeneous methods of measurement. A uniform approach to evaluating scanxiety will improve understanding of the phenomenon and help guide interventions

Scanxiety Conversations on Twitter: Observational Study

BackgroundScan-associated anxiety (or “scanxiety”) is commonly experienced by people having cancer-related scans. Social media platforms such as Twitter provide a novel source of data for observational research. ObjectiveWe aimed to identify posts on Twitter (or “tweets”) related to scanxiety, describe the volume and content of these tweets, and describe the demographics of users posting about scanxiety. MethodsWe manually searched for “scanxiety” and associated keywords in cancer-related, publicly available, English-language tweets posted between January 2018 and December 2020. We defined “conversations” as a primary tweet (the first tweet about scanxiety) and subsequent tweets (interactions stemming from the primary tweet). User demographics and the volume of primary tweets were assessed. Conversations underwent inductive thematic and content analysis. ResultsA total of 2031 unique Twitter users initiated a conversation about scanxiety from cancer-related scans. Most were patients (n=1306, 64%), female (n=1343, 66%), from North America (n=1130, 56%), and had breast cancer (449/1306, 34%). There were 3623 Twitter conversations, with a mean of 101 per month (range 40-180). Five themes were identified. The first theme was experiences of scanxiety, identified in 60% (2184/3623) of primary tweets, which captured the personal account of scanxiety by patients or their support person. Scanxiety was often described with negative adjectives or similes, despite being experienced differently by users. Scanxiety had psychological, physical, and functional impacts. Contributing factors to scanxiety included the presence and duration of uncertainty, which was exacerbated during the COVID-19 pandemic. The second theme (643/3623, 18%) was the acknowledgment of scanxiety, where users summarized or labeled an experience as scanxiety without providing emotive clarification, and advocacy of scanxiety, where users raised awareness of scanxiety without describing personal experiences. The third theme was messages of support (427/3623, 12%), where users expressed well wishes and encouraged positivity for people experiencing scanxiety. The fourth theme was strategies to reduce scanxiety (319/3623, 9%), which included general and specific strategies for patients and strategies that required improvements in clinical practice by clinicians or health care systems. The final theme was research about scanxiety (50/3623, 1%), which included tweets about the epidemiology, impact, and contributing factors of scanxiety as well as novel strategies to reduce scanxiety. ConclusionsScanxiety was often a negative experience described by patients having cancer-related scans. Social media platforms like Twitter enable individuals to share their experiences and offer support while providing researchers with unique data to improve their understanding of a problem. Acknowledging scanxiety as a term and increasing awareness of scanxiety is an important first step in reducing scanxiety. Research is needed to guide evidence-based approaches to reduce scanxiety, though some low-cost, low-resource practical strategies identified in this study could be rapidly introduced into clinical care