Patient and caregiver shared experiences of pulmonary fibrosis (PF): A systematic literature review.

Pulmonary Fibrosis (PF) describes a group of lung diseases characterised by progressive scarring (fibrosis). Symptoms worsen over time and include breathlessness, tiredness, and cough, giving rise to psychological distress. Significant morbidity accompanies PF, so ensuring patients' care needs are well defined and provided for, represents an important treatment strategy. The purpose of this systematic review was to synthesise what is currently known about the psychosocial morbidity, illness experience and needs of people with pulmonary fibrosis and their informal caregivers. Eight databases (MEDLINE, EMBASE, PUBMED, Cochrane database of Systematic reviews (CDSR), Web of Science Social Sciences Citation Index, PsycINFO, PsycARTICLES and CINAHL) were used to identify studies exploring the supportive needs of adults with PF and/or their caregivers. Methodological quality was assessed using the Mixed Methods Appraisal Tool. 53 studies were included, the majority using qualitative methodology (79 %, 42/53), 6 as part of mixed methodological studies. Supportive care needs were mapped to eight domains using an a priori framework analysis. Findings highlight a lack of psychological support throughout the course of the illness, misconceptions about and barriers to, the provision of palliative care despite its potential positive impacts. Patients and caregivers express a desire for greater disease specific education and information provision throughout the illness. Trials of complex interventions are needed to address the unique set of challenges for patients and carers living with PF.

A scoping review of the unmet needs of patients diagnosed with idiopathic pulmonary fibrosis (IPF).

AIMS: Patients diagnosed with idiopathic pulmonary fibrosis (IPF) have a high symptom burden and numerous needs that remain largely unaddressed despite advances in available treatment options. There is a need to comprehensively identify patients' needs and create opportunities to address them. This scoping review aimed to synthesise the available evidence and identify gaps in the literature regarding the unmet needs of patients diagnosed with IPF. METHODS: The protocol for the review was registered with Open Science Framework (DOI 10.17605/OSF.IO/SY4KM). A systematic search was performed in March 2022, in CINAHL, MEDLINE, Embase, PsychInfo, Web of Science Core Collection and ASSIA Applied Social Science Index. A comprehensive review of grey literature was also completed. Inclusion criteria included patients diagnosed with IPF and date range 2011-2022. A range of review types were included. Data was extracted using a data extraction form. Data was analysed using descriptive and thematic analysis. A total of 884 citations were reviewed. Ethical approval was not required. RESULTS: 52 citations were selected for final inclusion. Five themes were identified: 1.) psychological impact of an IPF diagnosis. 2.) adequate information and education: at the right time and in the right way. 3.) high symptom burden support needs. 4.) referral to palliative care and advance care planning (ACP). 5.) health service provision-a systems approach. CONCLUSION: This review highlights the myriad of needs patients with IPF have and highlights the urgent need for a systems approach to care, underpinned by an appropriately resourced multi-disciplinary team. The range of needs experienced by patients with IPF are broad and varied and require a holistic approach to care including targeted research, coupled with the continuing development of patient-focused services and establishment of clinical care programmes.

Patient perspectives on home-spirometry in interstitial lung disease: a qualitative co-designed study.

BACKGROUND: Opportunities for home-monitoring are increasing exponentially. Home- spirometry is reproducible and reliable in interstitial lung disease (ILD), yet patients' experiences are not reported. Given the morbidity and mortality associated with ILDs, maintaining health-related quality-of-life is vital. We report our findings from a codesigned, qualitative study capturing the perspectives and experiences of patients using home-spirometry in a UK regional ILD National Health Service England (NHSE) commissioned service. METHODS: Patients eligible for home-spirometry as routine clinical care, able to give consent and able to access a smart phone were invited to participate. In-depth, semistructured interviews were conducted at serial time points (baseline, 1, 3 and 6 months), recorded, transcribed and analysed thematically. RESULTS: We report on the experiences of 10 recruited patients (8 males; median age 66 years, range 50-82 years; 7 diagnosed with idiopathic pulmonary fibrosis, 3 other ILDs) who generally found spirometry convenient and easy to use, but their relationships with forced vital capacity results were complex. Main themes emerging were: (1) anticipated benefits-to identify change, trigger action and aid understanding of condition; (2) needs-clinical oversight and feedback, understanding of results, ownership, need for data and a need 'to know'; (3) emotional impact-worry, reassurance, ambivalence/conflicting feelings, reminder of health issues, indifference; (4) ease of home-spirometry-simplicity, convenience and (5) difficulties with home-spirometry-technical issues, technique, physical effort. CONCLUSION: Home-spirometry has many benefits, but in view of the potential risks to psychological well-being, must be considered on an individual basis. Informed consent and decision-making are essential and should be ongoing, acknowledging potential limitations as well as benefits. Healthcare support is vital.

Patient research priority setting partnership in human T-cell lymphotropic virus type I.

INTRODUCTION: Human T-cell lymphotropic virus type 1 (HTLV-1) is a chronic infection affecting 5-10 million people worldwide. Ten percent develop HTLV-1-associated diseases, and 3%-5% develop HTLV-1-associated myelopathy (HAM)/tropical spastic paraparesis. Low health-related quality of life (HRQoL) is a significant concern for those with HTLV-1, and little is known about how it impacts daily life or what patients need from healthcare services. To address this, we report on patient involvement workshops aimed at identifying research priorities for HTLV-1 health service provision. METHODS: Participants recruited through HTLV-1 clinics in England attended six 90-min virtual workshops over 10 months, and two 60-min consolidation workshops. Content developed iteratively from topic focussed group discussions. All workshops were video-recorded with consent, transcribed verbatim and thematically analysed. Using consensus voting rounds, participants individually ranked their top six and then collectively their top three research priorities from the themes inferred from the analysis. A final feedback session explored the experiences of participating in the workshops. FINDINGS: Twenty-seven people with HTLV-1 engaged with the workshops with up to 22 participants attending each meeting. The majority were diagnosed with HAM (n = 22). The top three research priorities were identified as understanding disease progression, psychosocial wellbeing, and information and knowledge. Participants valued being asked to set research priorities that directly addressed their needs and enjoyed the workshops. They stressed the importance of patient advocates for promoting research that positively impacts everyday life. CONCLUSION: This is the first of this type of research engagement with people with HTLV-1 in the United Kingdom. Participants identified several avenues of investigation that could lead to improvements in healthcare services and HRQoL. Participants believed the workshops signified the start of a conversation to progress person-centred and meaningful research in HTLV-1. PATIENT OR PUBLIC CONTRIBUTION: People living with HTLV-1 were involved in the iterative design, conduct, analysis, writing and dissemination of this project through the patient involvement workshops. As a result of this engagement, a patient led advisory group has been set up to assist with the dissemination of the findings.

Exploration of the unmet needs of patients diagnosed with idiopathic pulmonary fibrosis: a scoping review protocol.

INTRODUCTION: Interstitial lung diseases consist of a range of lung disorders, the most prevalent being idiopathic pulmonary fibrosis (IPF). IPF is a chronic, progressive disease, resulting in loss of lung function and potentially significant impacts on quality of life. There is an increasing need to address unmet needs in this population as there is evidence that unmet needs may impact quality of life and health outcomes. The key objective of this scoping review is to define the unmet needs of patients living with a diagnosis of IPF and to identify gaps in the literature relating to unmet needs. Findings will inform the development of services and the introduction of patient-centred clinical care guidelines for IPF. METHODS AND ANALYSIS: This scoping review is guided by the methodological framework for conducting scoping reviews developed by the Joanna Briggs Institute. The Preferred Reporting Items for Systematic Reviews and Meta-Analyses extension for Scoping Reviews checklist is used for guidance. The following databases will be searched: CINAHL, MEDLINE, PsycINFO, Web of Science, Embase and ASSIA and include a comprehensive grey literature search. The review will report on adult patients >18 with a diagnosis of IPF or pulmonary fibrosis and be limited to publications from 2011 onwards, with no language restrictions applied. Two independent reviewers will screen articles in consecutive stages for relevance against the inclusion and exclusion criteria. Data will be extracted using a predefined data extraction form and analysed using descriptive and thematic analysis. Findings will be presented in tabular form, coupled with a narrative summary of the evidence. ETHICS AND DISSEMINATION: Ethics approval is not required for this scoping review protocol. We will disseminate our findings using traditional approaches that include open access peer-reviewed publications and scientific presentations.

Patient Experience of Systemic Sclerosis-Related Calcinosis: An International Study Informing Clinical Trials, Practice, and the Development of the Mawdsley Calcinosis Questionnaire.

Systemic sclerosis (SSc) -related calcinosis can be a debilitating, constantly painful, poorly understood vascular complication of calcium hydroxyapatite deposition in soft tissue structures that affects approximately 40% of both limited and diffuse cutaneous SSc subtypes. This publication describes the iterative and multitiered international qualitative investigations that yielded remarkable insights into natural history, daily experience, and complications of SSc-calcinosis providing pivotal information for health management. Patient-driven question development and field testing, according to Food and Drug Administration guidance, propelled the development of a patient-reported outcome measure for SSc-calcinosis, the Mawdsley Calcinosis Questionnaire.

Sarcoidosis: Updates on therapeutic drug trials and novel treatment approaches.

Sarcoidosis is a systemic granulomatous inflammatory disease of unknown etiology. It affects the lungs in over 90% of patients yet extra-pulmonary and multi-organ involvement is common. Spontaneous remission of disease occurs commonly, nonetheless, over 50% of patients will require treatment and up to 30% of patients will develop a chronic progressive non-remitting disease with marked pulmonary fibrosis leading to significant morbidity and death. Guidelines outlining an immunosuppressive treatment approach to sarcoidosis were recently published, however, the strength of evidence behind many of the guideline recommended drugs is weak. None of the drugs currently used for the treatment of sarcoidosis have been rigorously studied and prescription of these drugs is often based on off-label" indications informed by experience with other diseases. Indeed, only two medications [prednisone and repository corticotropin (RCI) injection] currently used in the treatment of sarcoidosis are approved by the United States Food and Drug Administration. This situation results in significant reimbursement challenges especially for the more advanced (and often more effective) drugs that are favored for severe and refractory forms of disease causing an over-reliance on corticosteroids known to be associated with significant dose and duration dependent toxicities. This past decade has seen a renewed interest in developing new drugs and exploring novel therapeutic pathways for the treatment of sarcoidosis. Several of these trials are active randomized controlled trials (RCTs) designed to recruit relatively large numbers of patients with a goal to determine the safety, efficacy, and tolerability of these new molecules and therapeutic approaches. While it is an exciting time, it is also necessary to exercise caution. Resources including research dollars and most importantly, patient populations available for trials are limited and thus necessitate that several of the challenges facing drug trials and drug development in sarcoidosis are addressed. This will ensure that currently available resources are judiciously utilized. Our paper reviews the ongoing and anticipated drug trials in sarcoidosis and addresses the challenges facing these and future trials. We also review several recently completed trials and draw lessons that should be applied in future.

Interstitial lung disease and specialist palliative care access: a healthcare professionals survey.

BACKGROUND: Fibrotic interstitial lung disease is an incurable disease with poor prognosis. We aimed to understand factors affecting decisions regarding referrals to specialist palliative care services and to address barriers and facilitators to referrals from healthcare professionals' perspectives. METHODS: A survey study of healthcare professionals, including respiratory physicians, interstitial lung disease nurse specialists, respiratory nurse specialists and palliative care physicians, was conducted using a questionnaire, entailing 17 questions. RESULTS: Thirty-six respondents, including 15 interstitial lung disease nurse specialists completed the questionnaire. Symptom control, psychological/spiritual support, general deterioration and end-of-life care were the most common reasons for referrals to specialist palliative care services. Most respondents felt confident in addressing palliative care needs and discussing palliative care with patients. A few participants emphasised that experienced respiratory nurse specialists are well placed to provide symptom management and to ensure continuity of patient care. Participants reported that access to palliative care could be improved by increasing collaborative work between respiratory and palliative care teams. CONCLUSIONS: Most respondents felt that enhancing access to specialist palliative care services would benefit patients. However, palliative care and respiratory care should not be considered as mutually exclusive and multidisciplinary approach is recommended.

Home spirometry in patients with idiopathic pulmonary fibrosis: data from the INMARK trial.

BACKGROUND: Data from the INMARK trial were used to investigate the feasibility and validity of home spirometry as a measure of lung function decline in patients with idiopathic pulmonary fibrosis (IPF). METHODS: Subjects with IPF and preserved forced vital capacity (FVC) were randomised to receive nintedanib or placebo for 12 weeks followed by open-label nintedanib for 40 weeks. Clinic spirometry was conducted at baseline and weeks 4, 8, 12, 16, 20, 24, 36 and 52. Subjects were asked to perform home spirometry at least once a week and ideally daily. Correlations between home- and clinic-measured FVC and rates of change in FVC were assessed using Pearson correlation coefficients. RESULTS: In total, 346 subjects were treated. Mean adherence to weekly home spirometry decreased over time but remained above 75% in every 4-week period. Over 52 weeks, mean adherence was 86%. Variability in change from baseline in FVC was greater when measured by home rather than clinic spirometry. Strong correlations were observed between home- and clinic-measured FVC at all time-points (r=0.72-0.84), but correlations between home- and clinic-measured rates of change in FVC were weak (r=0.26 for rate of decline in FVC over 52 weeks). CONCLUSION: Home spirometry was a feasible and valid measure of lung function in patients with IPF and preserved FVC, but estimates of the rate of FVC decline obtained using home spirometry were poorly correlated with those based on clinic spirometry.

An epithelial biomarker signature for idiopathic pulmonary fibrosis: an analysis from the multicentre PROFILE cohort study.

BACKGROUND: Idiopathic pulmonary fibrosis (IPF) is a progressive, fatal disorder with a variable disease trajectory. The aim of this study was to assess potential biomarkers to predict outcomes for people with IPF. METHODS: PROFILE is a large prospective longitudinal cohort of treatment-naive patients with IPF. We adopted a two-stage discovery and validation design using patients from the PROFILE cohort. For the discovery analysis, we examined 106 patients and 50 age and sex matched healthy controls from Nottingham University Hospitals NHS Trust and the Royal Brompton Hospital. We did an unbiased, multiplex immunoassay assessment of 123 biomarkers. We further investigated promising novel markers by immunohistochemical assessment of IPF lung tissue. In the validation analysis, we examined samples from 206 people with IPF from among the remaining 212 patients recruited to PROFILE Central England. We used the samples to attempt to replicate the biomarkers identified from the discovery analysis by use of independent immunoassays for each biomarker. We investigated the predictive power of the selected biomarkers to identify individuals with IPF who were at risk of progression or death. The PROFILE studies are registered on ClinicalTrials.gov, numbers NCT01134822 (PROFILE Central England) and NCT01110694 (PROFILE Royal Brompton Hospital). FINDINGS: In the discovery analysis, we identified four serum biomarkers (surfactant protein D, matrix metalloproteinase 7, CA19-9, and CA-125) that were suitable for replication. Histological assessment of CA19-9 and CA-125 suggested that these proteins were markers of epithelial damage. Replication analysis showed that baseline values of surfactant protein D (46·6 ng/mL vs 34·6 ng/mL, p=0·0018) and CA19-9 (53·7 U/mL vs 22·2 U/mL; p<0·0001) were significantly higher in patients with progressive disease than in patients with stable disease, and rising concentrations of CA-125 over 3 months were associated with increased risk of mortality (HR 2·542, 95% CI 1·493-4·328, p=0·00059). INTERPRETATION: We have identified serum proteins secreted from metaplastic epithelium that can be used to predict disease progression and death in IPF. FUNDING: GlaxoSmithKline R&D and the UK Medical Research Council.

Palliative care in interstitial lung disease: living well.

Progressive fibrotic interstitial lung diseases (ILDs) are characterised by major reductions in quality of life and survival and have similarities to certain malignancies. However, palliative care expertise is conspicuously inaccessible to many patients with ILD. Unmet patient and caregiver needs include effective pharmacological and psychosocial interventions to improve quality of life throughout the disease course, sensitive advanced care planning, and timely patient-centred end-of-life care. The incorrect perception that palliative care is synonymous with end-of-life care, with no role earlier in the course of ILD, has created a culture of neglect. Interventions that aim to improve life expectancy are often prioritised without rigorous assessment of the individual's health and psychosocial needs, thereby inadvertently reducing quality of life. As in malignant disorders, radical interventions to slow disease progression and palliative measures to improve quality of life should both be prioritised. Efficient patient-centred models of palliative care must be validated, taking into account religious and cultural differences, as well as variability of resources. Effective implementation of palliative care for ILD will require multidisciplinary participation from clinicians, specialist nurses, psychologists, social workers, and, in some countries, non-governmental faith and community-based organisations with access to palliative care expertise.

Unmet needs in the treatment of idiopathic pulmonary fibrosis-insights from patient chart review in five European countries.

BACKGROUND: Two antifibrotic drugs, pirfenidone and nintedanib, are approved by the European Medicines Agency and the US Food and Drug Administration for the treatment of idiopathic pulmonary fibrosis (IPF). In this analysis, treatment patterns of European patients with IPF were investigated to understand antifibrotic prescribing and identify unmet needs in IPF treatment practice. METHODS: Between February and March 2016, respiratory physicians from France, Germany, Italy, Spain, and the UK participated in an online questionnaire designed to collect information on IPF treatment patterns in patients under their care. Patients were categorized as treated (received approved antifibrotics) or untreated (did not receive approved antifibrotics, but may have received other unapproved therapies). Classification of IPF diagnosis (confirmed/suspected) and severity ('mild'/'moderate'/'severe') for each patient was based on the individual physician's report. Patients' perspectives were not recorded in this study. RESULTS: In total, 290 physicians responded to the questionnaire. Overall, 54% of patients with IPF did not receive treatment with an approved antifibrotic. More patients had a confirmed IPF diagnosis in the treated (84%) versus the untreated (51%) population. Of patients with a confirmed diagnosis, 40% did not receive treatment. The treated population was younger than the untreated population (67 vs 70 years, respectively; p ≤ 0.01), with more frequent multidisciplinary team evaluation (83% vs 57%, respectively; p ≤ 0.01). A higher proportion of untreated patients had forced vital capacity > 80% at diagnosis versus treated patients. Of patients with 'mild' IPF, 71% did not receive an approved antifibrotic versus 41% and 60% of patients with 'moderate' and 'severe' IPF, respectively. CONCLUSIONS: Despite the availability of antifibrotic therapies, many European patients with confirmed IPF do not receive approved antifibrotic treatment. Importantly, there appears to be a reluctance to treat patients with 'mild' or 'stable' disease, and instead adopt a 'watch and wait' approach. More education is required to address diagnostic uncertainty, poor understanding of IPF and its treatments, and issues of treatment access. There is a need to increase physician awareness of the benefits associated with antifibrotic treatment across the spectrum of IPF severity.

Cough in idiopathic pulmonary fibrosis.

Many patients with idiopathic pulmonary fibrosis (IPF) complain of chronic refractory cough. Chronic cough is a distressing and disabling symptom with a major impact on quality of life. During recent years, progress has been made in gaining insight into the pathogenesis of cough in IPF, which is most probably "multifactorial" and influenced by mechanical, biochemical and neurosensory changes, with an important role for comorbidities as well. Clinical trials of cough treatment in IPF are emerging, and cough is increasingly included as a secondary end-point in trials assessing new compounds for IPF. It is important that such studies include adequate end-points to assess cough both objectively and subjectively. This article summarises the latest insights into chronic cough in IPF. It describes the different theories regarding the pathophysiology of cough, reviews the different methods to assess cough and deals with recent and future developments in the treatment of cough in IPF.

Daily Home Spirometry: An Effective Tool for Detecting Progression in Idiopathic Pulmonary Fibrosis.

RATIONALE: Recent clinical trial successes have created an urgent need for earlier and more sensitive endpoints of disease progression in idiopathic pulmonary fibrosis (IPF). Domiciliary spirometry permits more frequent measurement of FVC than does hospital-based assessment, which therefore affords the opportunity for a more granular insight into changes in IPF progression. OBJECTIVES: To determine the feasibility and reliability of measuring daily FVC in individuals with IPF. METHODS: Subjects with IPF were given handheld spirometers and instruction on how to self-administer spirometry. Subjects recorded daily FEV1 and FVC for up to 490 days. Clinical assessment and hospital-based spirometry was undertaken at 6 and 12 months, and outcome data were collected for 3 years. MEASUREMENTS AND MAIN RESULTS: Daily spirometry was recorded by 50 subjects for a median period of 279 days (range, 13-490 d). There were 18 deaths during the active study period. Home spirometry showed excellent correlation with hospital-obtained readings. The rate of decline in FVC was highly predictive of outcome and subsequent mortality when measured at 3 months (hazard ratio [HR], 1.040; 95% confidence interval [CI], 1.021-1.062; P ≤ 0.001), 6 months (HR, 1.024; 95% CI, 1.014-1.033; P < 0.001), and 12 months (HR, 1.012; 95% CI, 1.007-1.016; P = 0.001). CONCLUSIONS: Measurement of daily home spirometry in patients with IPF is highly clinically informative and is feasible to perform for most of these patients. The relationship between mortality and rate of change of FVC at 3 months suggests that daily FVC may be of value as a primary endpoint in short proof-of-concept IPF studies.

Qualitative European survey of patients with idiopathic pulmonary fibrosis: patients' perspectives of the disease and treatment.

BACKGROUND: 'Living with IPF and an exploration of Esbriet® - a new treatment' was an exploratory, qualitative, real-world survey of European patients with idiopathic pulmonary fibrosis (IPF) who were receiving treatment with pirfenidone prior to its commercial availability. The aim of the survey was to probe the impact of IPF on patients' quality of life; the role of healthcare professionals and caregivers; the information needs of both patients and their caregivers; and patients' perceptions of pirfenidone as a new treatment option for IPF. METHODS: Patients from the UK, Germany and Italy, with a diagnosis of IPF (duration >3 months), who were being treated with pirfenidone, were recruited from patient support groups, specialist centres and advocacy groups. Semi-structured, qualitative, in-depth patient interviews of 1-h duration were conducted by an independent researcher. Patients were initially asked about their experiences of living with IPF and then prompted to describe their experiences of taking pirfenidone. Techniques utilised included: the bubble-speech technique; the icon cards projective exercise; and the free association exercise. All interviews were transcribed and analysed by an independent researcher. RESULTS: Forty-five patients (71% male) were interviewed (mean age 68.5 years; mean time since diagnosis 3.5 years); 87% of patients reported that diagnosis took >1 year. Patients reported that IPF had a significant physical and emotional impact on their quality of life. The beneficial role played by caregivers and interstitial lung disease specialist nurses (where available) was specifically highlighted. Although most patients were keen for information on IPF, this was often of poor quality, out of date, or in English only. Patients' perceptions of pirfenidone were largely positive and associated with 'hope' but were also influenced by the level of side effects experienced. CONCLUSIONS: This survey highlights the impact of IPF on patients' lives, and the need to adequately support both patients and their caregivers. These findings demonstrate the value of seeking patients' perspectives of a chronic disease such as IPF and how this information can be used to guide improvements in care, to best support the needs of patients with this devastating condition.

The need for patient-centred clinical research in idiopathic pulmonary fibrosis.

Patient-centredness is an accepted term and is perceived by healthcare professionals to be morally and ethically desirable. We are motivated by the belief that this approach will improve the patient-professional experience of the decision-making process and improve health outcomes. We acknowledge that patients, either as participants or as co-investigators, have positive contributions to make to research. As the idiopathic pulmonary fibrosis (IPF) community enters a new era of clinical research activity we consider that there is greater capacity for patient involvement and partnership.Patient involvement in research can be optimised through collaborations in the research design, study conduct, and dissemination. There is increasing interest in using patient- reported outcomes (PROs), such as health-related quality of life, and symptoms measures to inform decision-making and ensure patient perspectives are taken into account. PROs are an essential component of specialist IPF services, to monitor and improve care delivery and to measure and benchmark performance. In clinical trials, PROs can additionally be used to define entry criteria, evaluate efficacy of an intervention, and evaluate adverse events. We suggest that there is a much wider scope for including patient-centred PROs in clinical research and for creative thought in developing patient co-investigator roles.Participation in research activity requires highly refined decision-making processes, particularly in a condition such as IPF, which has an often unpredictable trajectory. The IPF research landscape has changed and the design and conduct of clinical trials in IPF requires some radical rethinking. It is accepted that involving patients in the role of co-investigators will impact the research questions we ask and result in study designs that are patient-centred. IPF clinical trials have been hindered by the lack of availability of validated, disease-specific questionnaires. A conservative approach appears to have been taken to the inclusion of generic symptom or quality of life measures as PRO endpoints. Thus, the impact of new drugs on the quality of life of research participants demonstrates only minimal benefit. It is time to refocus on a patient-centred approach with regards to the co-investigator role, PRO development, and research participants.

FDA Approval Summary: Olaparib Monotherapy in Patients with Deleterious Germline BRCA-Mutated Advanced Ovarian Cancer Treated with Three or More Lines of Chemotherapy.

On December 19, 2014, the FDA approved olaparib capsules (Lynparza; AstraZeneca) for the treatment of patients with deleterious or suspected deleterious germline BRCA-mutated (gBRCAm) advanced ovarian cancer who have been treated with three or more prior lines of chemotherapy. The BRACAnalysis CDx (Myriad Genetic Laboratories, Inc.) was approved concurrently. An international multicenter, single-arm trial enrolled 137 patients with measurable gBRCAm-associated ovarian cancer treated with three or more prior lines of chemotherapy. Patients received olaparib at a dose of 400 mg by mouth twice daily until disease progression or unacceptable toxicity. The objective response rate (ORR) was 34% with median response duration of 7.9 months in this cohort. The most common adverse reactions (≥20%) in patients treated with olaparib were anemia, nausea, fatigue (including asthenia), vomiting, diarrhea, dysgeusia, dyspepsia, headache, decreased appetite, nasopharyngitis/pharyngitis/upper respiratory infection, cough, arthralgia/musculoskeletal pain, myalgia, back pain, dermatitis/rash, and abdominal pain/discomfort. Myelodysplatic syndrome and/or acute myeloid leukemia occurred in 2% of the patients enrolled on this trial.