Smoking, Diabetes Mellitus, and Previous Cardiovascular Disease as Predictors of Anticancer Treatment-Induced Cardiotoxicity in Non-Small-Cell Lung Cancer: A Real-World Study.

PURPOSE: Cardiotoxicity is a common and under-reported side effect of tyrosine-kinase inhibitors (TKI) and immune checkpoint inhibitors (ICI). Baseline risk factors may help in risk-stratifying patients at increased risk of cardiotoxicity. This real-world study investigated the effects of baseline risk factors in cardiotoxicity on patients with non-small-cell lung cancer (NSCLC) treated with TKIs and ICIs. METHODS: This is a retrospective study carried out at The Royal Marsden Hospital, UK. Newly diagnosed patients with localized or metastatic NSCLC who received anticancer therapy with TKIs and/or ICIs were eligible. Patients who received only chemotherapy were excluded. Patients were followed up from the time of diagnosis until death or discharge. The relationship between cardiotoxicity and risk factors were tested by logistic regression. RESULTS: Of 88/451 (19.5%) patients developed cardiotoxicity. Risk factors hypothesized to have a causal relationship with anticancer treatment-induced cardiotoxicity were analyzed. Cardiotoxicity risk was increased with prior diabetes mellitus (OR = 1.93, 95% CI, 1.04-3.61, P = .038), history of smoking (OR = 1.91, 95% CI, 1.13-3.22, P = .016) and presence of baseline cardiovascular disease (OR = 2.03, 95% CI, 1.13-3.64, P = .018). The risk of developing cardiotoxicity increased in patients for smokers with diabetes mellitus (OR = 3.03, 95% CI, 1.40-6.55, P < .01) and for smokers with previous cardiovascular disease (OR = 1.99, 95% CI, 1.03-3.84, P = .041). CONCLUSION: Diabetes mellitus, smoking and baseline cardiovascular disease may synergistically contribute to cardiotoxicity when a patient is exposed to potentially cardiotoxic anticancer agents. Risk stratification at baseline may improve cardio-oncology care.

Multiple cardiotoxicities during osimertinib therapy.

INTRODUCTION: The tyrosine-kinase inhibitor osimertinib is an oral anti-cancer agent that is used for the treatment of patients with metastatic non-small cell lung cancer harbouring sensitising EGFR mutations. Patients receiving osimertinib are at higher risk of developing cardiac toxicity, and here we present the case of a 72-year-old male who developed multiple cardiotoxicities during therapy (i.e. QTc prolongation, atrial fibrillation, heart failure). CASE REPORT: A 72-year-old white British, ex-smoker male patient was admitted to our cancer centre with adenocarcinoma of the lung. Afatinib, gefitinib, osimertinib, and carboplatin plus pemetrexed chemotherapy were the treatments he received. At the 15th month of osimertinib therapy, the patient developed QTc prolongation. Two weeks after the first incidence of QTc prolongation, electrocardiography showed rate-controlled atrial fibrillation. In addition to his atrial fibrillation, echocardiography revealed severely impaired left ventricular systolic function (left ventricular ejection fraction: 30%). MANAGEMENT AND OUTCOMES: Baseline to osimertinib, an electrocardiography investigation was carried out as per the protocol. Baseline drug history was reviewed and rosuvastatin was discontinued before initiating osimertinib as both drugs contribute to QTc prolongation. Dabigatran, bisoprolol, and digoxin were started for the treatment of atrial fibrillation. Ramipril and spironolactone were prescribed for the treatment of heart failure but osimertinib continued uneventfully. The patient died of non-small cell lung cancer. DISCUSSION: Recommendations for practical and clinically relevant baseline and on-treatment assessments are considered which may reduce the risk of cardiac toxicity during osimertinib therapy. These include baseline cardiac risk stratification, consideration of concomitant medications that may result in additive cardiac risk, and use of electrocardiography and echocardiography surveillance.

Investigating the efficacy of osimertinib and crizotinib in phase 3 clinical trials on anti-cancer treatment-induced cardiotoxicity: are real-world studies the way forward?

BACKGROUND.: Oncology clinical trials demonstrate the risk of cardiotoxicity but are not sufficient to reveal the true risk. In this article, we compared the incidence of cardiotoxicity of crizotinib and osimertinib from a real-world study to data reported by phase 3 clinical trials. METHODS.: Data from an ongoing real-world lung cancer study was used as a comparator. Patients were recruited retrospectively with the criteria of being diagnosed with non-small cell lung cancer and having received at least a course of treatment of tyrosine-kinase inhibitor and/or immune check-point inhibitor. Characteristics of the patients who developed cardiotoxicity associated with osimertinib and crizotinib in the real-world lung cancer study were analysed against the inclusion criteria of the corresponding phase 3 clinical trials. Variations of cardiotoxicity incidence among the real-world lung cancer study and clinical trials were investigated. RESULTS.: 18%, n = 37/206, of the patients developed cardiotoxicity. QTc prolongation was the most frequently observed cardiotoxicity (n = 12/37). Osimertinib and crizotinib were the most cardiotoxic agents, each responsible for seven cases of cardiotoxicity. FLAURA, AURA3, PROFILE 1007 and PROFILE 1014 were the included clinical trials for analysis. None of the patients who developed cardiotoxicity in the real-world study would have been eligible to participate in FLAURA and PROFILE 1014 study whereas n = 4/7 and n = 5/7 patients were eligible to participate in AURA3 and PROFILE 1007 trials, respectively. CONCLUSION.: Although phase 3 clinical trials play an important role in understanding the effectiveness and give insights on side-effect profiles, real-world studies can show the real risk of cardiotoxicity more accurately and realistically.

'A life in a day' simulation experience: perceptions of oncology nurses and pharmacy staff.

BACKGROUND: Due to an increase in patient numbers, more cancer patients are being reviewed by non-medical healthcare professionals (HCPs), and it is essential that they can empathise with patients and care for them holistically. 'A Life in a Day' is a role reversal simulation (RRS) which demonstrates the challenges, choices and impacts that cancer patients face every day, facilitated by a Smartphone application (app). This study focused on renal cell carcinoma (RCC) and was designed to evaluate the impact of RRS on participants from the British Oncology Pharmacy Association (BOPA) and the UK Oncology Nursing Society (UKONS), and identify any changes made to clinical practice as a result. METHOD: A survey was conducted via the app before and after the experience. Individual semi-structured interviews were conducted with participants over Microsoft Teams. RESULTS: Data from the survey showed that after the experience 97% of all participants strongly agreed that they 'feel empathy for RCC patients' and 90% strongly agreed that they 'feel inspired to place patients at the centre of their work'. There were 5 themes extrapolated from the qualitative data: Holistic understanding of Patients, Reflections on Practice, Changes in Practice, Outreach to Colleagues, Education & Training. CONCLUSION: Participants reported an increase in empathy for their patients which inspired them to make changes to their practice. This involved being more holistic in their care and taking on more responsibility. They recommended use of RRS for HCP training and continued professional development. They also suggested incorporation of RRS into the pharmacy undergraduate curriculum.

Histamine-2 (H2 ) antagonists can be safely removed from standard paclitaxel premedication regimens.

AIMS: The aim of this study is to investigate the rates of hypersensitivity reactions (HSRs) in patients receiving paclitaxel chemotherapy, with and without a histamine-2 (H2 ) antagonists. METHOD: This prospective, multi-centre, cohort study compared patients receiving paclitaxel treated with premedication regimens containing chlorphenamine, dexamethasone and an H2 antagonist vs patients treated without an H2 antagonist. Rates of HSRs were described and logistic multivariable regression was used to investigate any associations with H2 antagonist treatment, adjusting for confounding variables. RESULTS: A total of 1043 individuals were included in the study; of these, 638 (61%) patients received an H2 antagonist and 405 (49%) were not given an H2 antagonist. Incidence of HSR in the cohort treated with H2 antagonists was 11.31% (n = 70) vs 9.86% (n = 41) in the cohort without. There was no statistically significant difference between the rates of HSR observed in those receiving and not receiving an H2 antagonist (odds ratio 1.04, 95% CI 0.65, 1.66, P = .9). CONCLUSIONS: Results presented within the study are consistent with other recently published evidence to suggest that H2 antagonists do not confer any advantage as part of premedication regimens in reducing the incidence of HSR in patients treated with paclitaxel.

Biosimilars in supportive care.

PURPOSE OF REVIEW: This review covers recent publications relating to the use of biosimilar medicines in the supportive care of cancer patients, and broader publications focussed on the benefits and challenges of implementing biosimilars into clinical practice. RECENT FINDINGS: A metaanalysis and a number of systematic literature reviews have confirmed that the safety and efficacy of biosimilar versions of epoetin-α, filgrastim and infliximab are equivalent to those of their corresponding reference biologics. New guidelines have been issued concerning the interchangeability of biosimilars and the practice of substituting a biosimilar in place of a prescribed reference product. The introduction of biosimilars into a health system has been shown to improve patient access to treatment while also delivering cost savings, however, there are a number of barriers that can prevent or delay the adoption of biosimilars into clinical practice which must be overcome for the potential benefits of biosimilars to be realized. SUMMARY: There is a large amount of data to demonstrate that supportive care biosimilars are well tolerated and effective, with over 10 years of experience in Europe. We can learn from the challenges faced when introducing biosimilars into supportive care to facilitate the introduction of newer biosimilars into the treatment setting.

A survey of global biosimilar implementation practice conducted by the International Society of Oncology Pharmacy Practitioners.

Background: The International Society of Oncology Pharmacy Practitioners (ISOPP) Biosimilars Task Force was charged to develop educational activities and resources to assist members when implementing biosimilar medicines into their local practice. To facilitate the process, the task force conducted a survey in order to understand biosimilar implementation practice by ISOPP members across the world and the challenges that oncology pharmacists face when adopting biosimilars into their clinical practice. Methods: A cross-sectional survey was conducted between 20 April 2019 and 27 May 2019. Members of ISOPP and a number of national oncology pharmacy groups were invited to complete the survey. The survey contained 29 items and consisted of three sections: respondents' demographics, respondents' institutional practice relating to biosimilar implementation and post implementation practice at the respondents' institutions. Descriptive statistics were utilized to analyze the survey results. Results: A total of 265 ISOPP members were surveyed, with 50 members providing a response (response rate = 19%). In addition, 40 nonmembers participated in the survey, bringing the total to 90 respondents. The most common factors that influence the decision to implement use of a biosimilar as reported by respondents are medication costs/pricing (92%), available clinical data (73%), and product availability (63%). Respondents also commented on the barriers to biosimilar implementation at their institutions, which included a reluctance of prescribers to use biosimilars (due to the lack of familiarity or perceived inferiority), a reluctance to switch established patients from an originator to a biosimilar and the preferences of insurance companies or funding bodies. Conclusion: The results of this survey reinforce the need for greater education and training for health care professionals in the use of biosimilars, the importance of sharing good practice, and a need for standardization.

International Society of Oncology Pharmacy Practitioners global position on the use of biosimilars in cancer treatment and supportive care.

With the development of innovative cancer treatments over recent decades, the cost of cancer care has risen exponentially, limiting patient access to patented originator biotherapeutics in many countries. The introduction of biosimilars to the market has created new opportunities as well the need for changes in practice within healthcare institutions. A 'biosimilar' is a biotherapeutic product which is highly similar in terms of quality, safety and efficacy to an already licensed originator product. Although biosimilars lack clinically meaningful differences in therapeutic activity as compared to the originator product, these complex biological molecules are not considered identical chemical copies, unlike generics, and minor differences in molecular structure and inactive compounds may exist. A thorough understanding of these differences and their clinical implications is necessary for optimising medicines-use practices involving biosimilars. This position statement, developed by the International Society of Oncology Pharmacy Practitioners Biosimilars Taskforce, aims to provide the global oncology pharmacy community with guidance to support decisions around biosimilar use. The 11 statements cover the regulation and evaluation of biosimilars, practical issues around local implementation, the education of healthcare staff and patients, and the requirement for ongoing pharmacovigilance and outcome monitoring.

Assessing biosimilar education needs among oncology pharmacy practitioners worldwide: An ISOPP membership survey.

Background: The International Society of Oncology Pharmacy Practitioners (ISOPP) Biosimilar Task Force was charged to develop educational resources to address the learning needs related to biosimilars use of oncology pharmacy practitioners. To facilitate the process, the task force conducted a survey in order to identify unmet education needs as well as barriers for obtaining biosimilar education among oncology pharmacy practitioners. Methods: A cross sectional survey was conducted between 10 December 2018 and 18 February 2019. Members of International Society of Oncology Pharmacy Practitioners and national oncology pharmacy groups were invited to complete the survey. The survey contained 22 items and consisted of four sections. Descriptive statistics were utilized to analyze the survey results. Results: A total of 363 International Society of Oncology Pharmacy Practitioners members were surveyed, with 75 members providing a response (response rate = 21%). In addition, 11 non-International Society of Oncology Pharmacy Practitioners members also participated in the survey, bringing the total to 86 respondents. The top three areas in which respondents reported learning needs included evaluating comparative efficacy of a biosimilar to an originator's product (74.4%), managing the switchover to a biosimilar from the original product (74.4%), and understanding medication safety issues in relation to biosimilars use (73.3%). The most common challenges faced in obtaining education on biosimilars included limited financial support for education on biosimilar products (38.4%), heavy workload (31.4%), and inadequate educational resources (27.9%). Conclusion: This survey has identified numerous biosimilar learning needs as well as challenges faced in obtaining biosimilars education among oncology pharmacy practitioners. Educational activities should be created to address these learning needs, and innovative strategies should be considered to overcome practitioner's barriers in obtaining biosimilars education.

Staff sensitisation to therapeutic monoclonal antibodies resulting from workplace exposure: A case report.

Monoclonal antibodies were introduced to clinical practice in 1980s and play a vital role in a variety of diseases and clinical interventions including cancer, inflammatory disease, and ophthalmologic disease. There is a lack of substantial research or evidence on the effect of occupational exposure on staff, leading many staff to have significant concerns about what is a safe level of exposure, especially given their increasing availability and use. This report describes a case in which a nurse became sensitised to monoclonal antibodies as a result of preparing and administering them in a clinical area, and the subsequent actions taken in response to the incident to reduce the risk to staff.

The physical health of Indigenous and non-Indigenous patients participating in residential rehabilitation programs: a comparison study.

OBJECTIVE: To examine the differences in the physical health of Indigenous and non-Indigenous patients with severe mental illness (SMI) undergoing psychiatric rehabilitation. METHODS: An audit of the physical health of patients ( n = 361) in all publicly funded residential rehabilitation programs in Queensland was carried out in late 2014. Data collection focused on clinical and lifestyle factors associated with physical health. RESULTS: The prevalence of smoking, substance use and type 2 diabetes in Indigenous patients was significantly higher than rates found in non-Indigenous patients. Metabolic syndrome was also significantly higher in indigenous patients, with 66% of Indigenous patients compared to 46% of non-Indigenous patients meeting criteria for metabolic syndrome. CONCLUSIONS: Patients with SMI in residential rehabilitation programs have poor physical health. Our findings underscore the need for clinicians to develop and evaluate interventions aimed at improving the metabolic profile of those with SMI in residential rehabilitation programs. Historical factors and cultural traditions need to be considered when designing lifestyle interventions for Indigenous patients.

Continuous subcutaneous levetiracetam in the management of seizures at the end of life: a case report.

We report the case of a man who developed seizures on a background of recurrent metastatic squamous cell carcinoma with intracranial involvement. Initial seizure control with enteral levetiracetam was achieved, and when enteral and intravenous (i.v.) access was no longer available, a continuous subcutaneous infusion (CSCI) of levetiracetam successfully controlled his seizures without the need for sedating anticonvulsants. As a result, end-of-life care was able to be given with the patient retaining the ability to communicate with his family and healthcare staff. This report adds to the sparse but growing evidence base for the use of subcutaneous levetiracetam to manage seizures in palliative and end-of-life care.