Health-related quality of life scores of metastatic pancreatic cancer patients responsive to first line chemotherapy compared to newly derived EORTC QLQ-C30 reference values.

BACKGROUND: Metastatic pancreatic cancer (mPC) and its treatments significantly impact health-related quality of life (HRQoL). POLO, a randomized, double-blind, placebo-controlled phase 3 trial evaluated the efficacy of olaparib as maintenance therapy in germline BRCA mutated mPC patients who had not progressed during ≥16 weeks of first-line platinum-based chemotherapy. HRQoL was assessed using the EORTC QLQ-C30. To enhance score interpretation, we derived reference values for treatment-naïve mPC patients from the literature. METHODS: A targeted literature review identified EORTC QLQ-C30 baseline values in treatment-naïve mPC patients. Reference values were calculated by deriving means from studies meeting inclusion criteria, with scores from 0 to 100 (higher scores indicate better QoL/functioning but worse symptoms). For POLO patients, means were calculated using pooled baseline data across study arms. RESULTS: Four studies met inclusion criteria. Depending on the specific scale, sample sizes ranged from n = 466 to n = 639. Compared to newly derived reference values, POLO patients reported markedly better HRQoL scores at baseline across most scales, with eight scales showing differences of ≥10 points. POLO patients' HRQoL scores were often close to or better than general population norm data. CONCLUSIONS: This is the first study to systematically derive EORTC QLQ-C30 reference values for mPC. POLO patients had better HRQoL scores than those in the literature and similar to general population data. Comparatively high HRQoL of POLO patients are likely due to effects of prior first-line treatment and resolution of chemotherapy-related symptoms, response shift, or a combination. Newly derived reference values can enhance interpretation of mPC patients' HRQoL. TRIAL REGISTRATION: The POLO trial was registered on 9 July 2014 with ClinicalTrials.gov as NCT02184195.

Benefit-risk trade-offs in treatment choice in advanced HER2 negative breast cancer: patient and oncologist perspectives.

Aim: To evaluate which treatment attributes US patients and oncologists prioritize in HER2 negative advanced breast cancer (ABC). Methods: Preferences were assessed via a discrete choice experiment. Also, treatment goal statements were rated on an agreement scale. Results: Patients (n = 169) most valued improving overall survival (OS), followed by improving nausea and neuropathy. Oncologists (n = 117) most valued improving OS, followed by neuropathy and progression-free survival. Regarding treatment goals, oncologists (67%) perceived that patients are more focused on efficacy than quality of life; fewer patients (29%) agreed with this statement; 81% of oncologists and 51% of patients agreed that patients prefer oral treatment. Conclusion: Patients and oncologists were willing to accept increases in toxicities in exchange for efficacy improvements in HER2 negative ABC.

The goal of this study was to understand the preferences of patients and physicians for the benefits and risks associated with the treatment of advanced breast cancer that expresses normal amounts of the HER2 protein (termed as HER2 negative). Respondents completed an exercise where they compared two treatment options at a time that varied in their level of effectiveness and their potential for certain side effects and then selected the treatment option they most preferred. From this exercise, the treatment features that matter the most to patients and physicians were discovered. The most important treatment features for patients were lengthening life expectancy, decreasing the chance of experiencing nausea affecting appetite, and decreasing the chance of experiencing nerve damage involving numbness and/or pain, possibly severe, in hands and feet which may limit daily activities. The most important treatment features for physicians were lengthening life expectancy, decreasing the change of experiencing nerve damage involving numbness and/or pain, possibly severe, in hands and feet which may limit daily activities, and lengthening the time that cancer remains stable and does not worsen. Patients and physicians also rated how much they agreed with statements about their goals for treatment. While 67% of oncologists believed that their patients are more focused on killing the cancer than their quality of life, only 27% of patients were more focused on killing the cancer than their quality of life.

Patients' and oncologists' preferences for second-line maintenance PARP inhibitor therapy in epithelial ovarian cancer.

Aim: To understand the preferences of US patients and oncologists for PARP inhibitors as second-line maintenance (2LM) for epithelial ovarian cancer. Methods: A discrete choice experiment was conducted to assess the preferences of treatment attributes. Results: The most valued attributes were risk of grade 3/4 adverse events (AEs; patients, n = 204) and progression-free survival (PFS; oncologists, n = 151). To accept a 37% increased risk of grade 3/4 AEs, PFS would need to increase by 27.9 months (patients) and 6.3 months (oncologists). The least valued attributes were dosing form/frequency (patients) and grade 3/4 anemia risk (oncologists). Conclusion: Patients' and oncologists' willingness to make benefit-risk trade-offs in the 2LM setting suggests that the PFS gains observed in selected studies of poly (ADP-ribose) polymerase inhibitors in BRCA-mutated disease are worth the toxicity risk.

Plain language summary Maintenance therapy is a treatment option intended to keep ovarian cancer from coming back or getting worse for as long as possible after responding to chemotherapy. PARP inhibitors are a new type of maintenance therapy for ovarian cancer. This study aimed to understand the patients' and physicians' preferences for the benefits and risks associated with different PARP inhibitors used as maintenance therapy for ovarian cancer. Participants were asked to compare various treatment options based on their different safety profiles, effectiveness and form of medication (e.g., three capsules by mouth once a day versus two tablets by mouth twice a day), and then choose the treatment they most preferred. Through this exercise, the treatment features that mattered most to patients and physicians were identified. The most important treatment feature for patients was decreasing the chance of experiencing a serious side effect that requires medical intervention or hospitalization. In contrast, physicians valued lengthening the time that a cancer remains stable and does not worsen. To accept a 37% higher chance of experiencing a side effect that requires medical intervention or hospitalization, patients expect their cancer to remain stable and not worsen for an additional 28 months. This was a large difference from the 6 months that the physicians would consider as acceptable. The least important treatment features for patients are the amount of pills required per dose, the form of the given medication (e.g., tablet vs capsule) and the schedule of taking the treatment. On the other hand, physicians were least concerned about lowering the risk of experiencing low blood counts that, requiring medical intervention.

Epidemiological and clinical burden associated with plexiform neurofibromas in pediatric neurofibromatosis type-1 (NF-1): a systematic literature review.

PURPOSE: Patients with neurofibromatosis type-1 (NF-1) and associated plexiform neurofibromas (PNs) often have a high burden of illness owing to debilitating symptoms of these tumors and limited management options. To investigate this complex disease, a systematic literature review (SLR) was conducted on the epidemiology of pediatric NF-1 and associated PNs, the burden of illness, and outcomes of surgical resection of these tumors. METHODS: Searches of MEDLINE and Embase (from database inception to October 2019) and conference proceedings (2017-2019) were performed to identify relevant studies. The review methodology was informed by the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. RESULTS: Twenty studies were identified. Evidence confirmed NF-1 is rare but that occurrence may differ geographically. Only limited data on the birth incidence of NF-1 were identified. Prevalence estimates for pediatric NF-1 varied from one per 960 individuals (aged 17 years) to one per 5681 children (aged < 16 years) across five large registry/surveillance studies (each involving > 19,000 individuals). The prevalence of associated PNs was 0-29.6%. PNs carried increased mortality risk in pediatric NF-1 in both studies that explored this potential association. Patients with PNs reported high use of analgesics. The complication rate post-surgery for PNs was around 17-19%. The recurrence rate (18-68%) was dependent on the extent of excision achieved during surgery. CONCLUSIONS: Data suggest NF-1 is a rare disease with increased morbidity and mortality in children with associated PNs. Surgical outcomes for PNs are often poor. These findings suggest significant unmet needs in patients with NF-1-associated PNs.

Clinical and humanistic burden among pediatric patients with neurofibromatosis type 1 and plexiform neurofibroma in the USA.

PURPOSE: To assess clinical and humanistic burden among pediatric patients with neurofibromatosis type 1 (NF1) and plexiform neurofibroma (PN) in the USA. METHODS: NF1-PN patients aged 8-18 years (treatment-naïve or ≤ 1 month of selumetinib treatment) and their caregivers and caregivers of similar patients aged 2-7 years were recruited through the Children's Tumor Foundation to participate in an online cross-sectional survey (December 2020-January 2021). Caregivers provided data on patients' demographic and clinical characteristics and burden of debulking surgeries. Patients and caregivers provided self-reported or proxy responses to health-related quality of life (HRQoL) questions using validated instruments. RESULTS: Sixty-one patients and 82 caregivers responded to the survey. Median (range) age of patients was 11.5 (3-18) years, and 53.7% were female. Most were treatment-naïve (97.6%), with NF1-PN diagnosis for > 5 years (68.3%). Most patients (59.8%) had > 1 PN and 11.0% reporting > 5 PNs. Common NF1-PN symptoms included pain (64.6%), disfigurement (32.9%), and motor dysfunction (28.0%). Patients and caregiver proxies reported low overall HRQoL and reduced physical, emotional, social, and school functioning. Patients also reported considerable pain severity, interference, daily activity impairments, and movement difficulty. Few patients had received complete resections of their tumors (12.2%). 39.0% reported ≥ 1 debulking surgery, among whom, 15.6% had complications, and debulking surgery-related hospitalizations were common (53.1%). CONCLUSIONS: The clinical and humanistic burden among pediatric NF1-PN patients is substantial. While debulking surgeries are used for symptom management, they are associated with considerable clinical sequelae. Results highlight a need for improved disease management strategies.

Systematic Literature Review of the Epidemiology of Advanced Prostate Cancer and Associated Homologous Recombination Repair Gene Alterations.

PURPOSE: To characterize the global epidemiology of metastatic castration-sensitive prostate cancer (mCSPC), nonmetastatic castration-resistant prostate cancer (nmCRPC) and metastatic castration-resistant prostate cancer (mCRPC). Additionally, to assess the prevalence of homologous recombination repair gene alterations (HRRm) and their prognostic impact in advanced disease setting. MATERIALS AND METHODS: A systematic literature review of real-world evidence published from January 2009 through May 2019 was conducted to assess global epidemiology and clinical practice trends for mCSPC, nmCRPC, mCRPC and HRRm; 4,732 papers were systematically screened for inclusion. Ten conference proceedings from 2014 through 2019 were reviewed. RESULTS: Of the screened articles 22 relevant publications were identified for this paper. Six publications reported global epidemiology of advanced prostate cancer. The prevalence of nmCRPC was estimated as 1.1% to 12.3% of prostate cancer cases and for mCRPC 1.2% to 2.1% of prostate cancer cases. No mCSPC prevalence was captured. Sixteen publications investigated HRRm prevalence in advanced prostate cancer with the majority conducted in mCRPC assessed using next-generation sequencing of tissue and germline samples. In mCRPC, the highest prevalence HRRm in both germline (3.3%-6.0%) and somatic (5.0%-15.1%) was BRCA2. Five publications reported the prognostic impact of HRRm in advanced prostate cancer. CONCLUSIONS: Published real-world evidence quantifying the prevalence of advanced prostate cancer and HRRm beyond mCRPC is sparse. Published data on HRRm, specifically BRCA2, are consistent with published clinical trial data for poly (ADP-ribose) polymerase inhibitors in mCRPC. In mCRPC, real-world evidence suggests that patients with HRRm have different clinical outcomes to noncarriers. More data are needed to better understand real-world patient segmentation and clinical outcomes for biomarkers given increasing interest in profiling.

Health-Related Quality of Life of Patients with Metastatic Pancreatic Cancer: A Systematic Literature Review.

Background: Metastatic pancreatic cancer (mPaC) has a poor prognosis and available treatments provide only moderate improvements in survival. Preserving or improving health-related quality of life (HRQoL) is therefore an important treatment outcome for patients with mPaC. This systematic review identified HRQoL data in patients with mPaC before and after treatment, compared these with data from the general population, and reported the effects of different mPaC treatments on HRQoL. Methods: Searches were performed in Embase, PubMed, and the Cochrane Library from January 2008 to May 2021, and the articles identified were screened for HRQoL data in patients with mPaC. Abstracts from relevant congresses were also manually searched. Publications included were randomized controlled trials and observational studies written in English that reported HRQoL data for adult patients with non-resectable mPaC who were on or off treatment. Results: Thirty relevant publications were identified and HRQoL scores were collected. Overall, baseline mean scores from the European Organization for the Research and Treatment of Cancer Quality of Life Questionnaire-Core 30 (EORTC QLQ-C30), 5-dimension EuroQol questionnaire (EQ-5D), and Functional Assessment of Cancer Therapy-General (FACT-G) for newly diagnosed and previously treated patients with mPaC were worse than those of the general population. Baseline scores were generally better for previously treated patients than for newly diagnosed patients, indicating that mPaC treatments preserve or improve HRQoL. Identified publications also reported changes in HRQoL following first- or subsequent-line chemotherapy. When reported, 10 studies found improvements in overall HRQoL compared with baseline scores, four reported no changes in overall HRQoL after treatment, and six found deteriorations in overall HRQoL. Conclusion: Patients with mPaC had worse HRQoL than the general population. Available anti-cancer therapies can improve or preserve HRQoL.

Burden Among Caregivers of Pediatric Patients with Neurofibromatosis Type 1 (NF1) and Plexiform Neurofibroma (PN) in the United States: A Cross-Sectional Study.

INTRODUCTION: Patients with neurofibromatosis type 1 (NF1) may develop plexiform neurofibromas (PNs) that can cause disfigurement, pain, and dysfunction, and may even be life-threatening. Studies have indicated NF1-PN can substantially impact the quality of life (QoL) of pediatric patients. However, research on caregiver burden is scarce. METHODS: Caregivers of pediatric patients ages 2-18 years with NF1-PN in the USA were recruited through the Children's Tumor Foundation to participate in an online cross-sectional survey (December 2020-January 2021). Caregiver burden was measured using the Zarit Burden Interview (ZBI), and productivity loss from patientcare was measured using the Work Productivity and Activity Impairment questionnaire, adapted for caregiving (WPAI:CG). RESULTS: Ninety-five caregivers were recruited with a median age of 44.0 years. Most were female (88.4%), white/Caucasian (85.3%), and did not have NF1 or PN (86.3% and 89.5%, respectively). Commonly reported health conditions among caregivers include anxiety (48.4%) and depression (34.7%). On the ZBI (range 0-88; higher = greater burden), mean (SD) scores were 23.0 (13.8) and 12.7% of caregivers reported moderate-severe (scores 41-60) or severe burden (scores 61-88). Fifty-six caregivers were employed and working in the 7 days prior to completing the WPAI:CG. They reported missing an average of 6.9% of their working hours and an average reduction of 17.3% of on-the-job effectiveness, contributing to 22.3% loss in work productivity. Among all 95 caregivers, an average of 17.2% of regular daily activities were impaired. CONCLUSIONS: The burden among caregivers of pediatric patients with NF1-PN is considerable and underscores an unmet need for better disease management.

Estimating Productivity Loss from Breast and Non-Small-Cell Lung Cancer among Working-Age Patients and Unpaid Caregivers: A Survey Study Using the Multiplier Method.

Background. Traditional approaches to capturing health-related productivity loss (e.g., the human capital method) focus only on the foregone wages of affected patients, overlooking the losses caregivers can incur. This study estimated the burden of productivity loss among breast cancer (BC) and non-small-cell lung cancer (NSCLC) patients and individuals caring for such patients using an augmented multiplier method. Design. A cross-sectional survey of BC and NSCLC patients and caregivers measured loss associated with time absent from work (absenteeism) and reduced effectiveness (presenteeism). Respondents reported pre- and postcancer diagnosis income, hours worked, and time to complete tasks. Exploratory multivariable analyses examined correlations between respondents' clinical/demographic characteristics-including industry of employment-and postdiagnosis productivity. Results. Of 204 patients (104 BC, 100 NSCLC) and 200 caregivers (100 BC, 100 NSCLC) who completed the survey, 319 participants (162 BC, 157 NSCLC) working ≥40 wk/y prediagnosis were included in the analysis. More than one-third of the NSCLC (33%) and BC (43%) patients left the workforce postdiagnosis, whereas only 15% of caregivers did. The traditional estimate for the burden of productivity loss was 66% lower on average than the augmented estimate (NSCLC patients: 60%, BC patients: 69%, NSCLC caregivers: 59%, and BC caregivers: 73%). Conclusions. Although patients typically experience greater absenteeism, productivity loss incurred by caregivers is also substantial. Failure to account for such impacts can result in substantial underestimation of productivity gains novel cancer treatments may confer by enabling patients and caregivers to remain in the workforce longer. Our results underscore the importance of holistic approaches to understanding this impact on both patients and their caregivers and accounting for such considerations when making decisions about treatment and treatment value. Highlights: Cancer can have a profound impact on productivity. This study demonstrates how the disease affects not only patients but also the informal or unpaid individuals who care for patients.An augmented approach to calculating health-related productivity loss suggests that productivity impacts are much larger than previously understood.A more comprehensive understanding of the economic burden of cancer for both patients and their caregivers suggests the need for more support in the workplace for these individuals and a holistic approach to accounting for these impacts in treatment decision making.

Natural History and Disease Burden of Neurofibromatosis Type 1 with Plexiform Neurofibromas: A Systematic Literature Review.

Neurofibromatosis type 1 (NF1) is an incurable genetic condition that frequently includes the development of plexiform neurofibromas (PNs) in patients. A systematic literature review was conducted to identify data on the natural history, disease burden, and treatment patterns among patients diagnosed with NF1 and PN, as well as to identify evidence gaps in these areas. MEDLINE and MEDLINE In-Process, Embase, and Cochrane Library Searches were searched using predefined terms. Potential references underwent two phases of screening by two independent researchers. A total of 39 references focusing on populations of patients with both NF1 and PN were included in this review. The wide range of PN-related complications creates a substantial quality-of-life (QOL) burden for patients, including pain, social functioning, physical function impact, stigma, and emotional distress. The severe burden of NF1 with PN on the QOL of patients demonstrates the high unmet need for an effective treatment option that can reduce tumor burden and improve QOL. The heterogeneity of measurement tools used to evaluate QOL and the gap in data evaluating the health economic burden of PN should be the focus of future research.

Understanding Patient Perspectives on Medication Adherence in Asthma: A Targeted Review of Qualitative Studies.

Adherence to asthma medications is generally poor and undermines clinical outcomes. Poor adherence is characterized by underuse of inhaled corticosteroids (ICS), often accompanied by over-reliance on short-acting ß2-agonists for symptom relief. To identify drivers of poor medication adherence, a targeted literature search was performed in MEDLINE and EMBASE for articles presenting qualitative data evaluating medication adherence in asthma patients (≥12 years old), published from January 1, 2012 to February 26, 2018. A thematic analysis of 21 relevant articles revealed several key themes driving poor medication adherence, including asthma-specific drivers and more general drivers common to chronic diseases. Due to the episodic nature of asthma, many patients felt that their daily life was not substantially impacted; consequently, many harbored doubts about the accuracy of their diagnosis or were in denial about the impact of the disease and, in turn, the need for long-term treatment. This was further compounded by poor patient-physician communication, which contributed to suboptimal knowledge about asthma medications, including lack of understanding of the distinction between maintenance and reliever inhalers, suboptimal inhaler technique, and concerns about ICS side effects. Other drivers of poor medication adherence included the high cost of asthma medication, general forgetfulness, and embarrassment over inhaler use in public. Overall, patients' perceived lack of need for asthma medications and medication concerns, in part due to suboptimal knowledge and poor patient-physician communication, emerged as key drivers of poor medication adherence. Optimal asthma care and management should therefore target these barriers through effective patient- and physician-centered strategies.

Usage Patterns of Short-Acting ß2-Agonists and Inhaled Corticosteroids in Asthma: A Targeted Literature Review.

Despite the availability of effective asthma treatments, some patients are poorly controlled because of overreliance on short-acting ß2-agonists (SABAs) and underuse of inhaled corticosteroids (ICSs). To identify patient characteristics and outcomes associated with SABA overreliance and ICS underuse, we conducted a targeted literature review of the quantitative evidence on asthma medication use. Articles evaluating SABA and/or ICS use in patients with asthma (aged ≥12 years), published between January 2012 and March 2018, were identified using MEDLINE and EMBASE. We observed that studies classified SABA usage as "overuse," "high use," "excess use," "extreme overuse," "suboptimal use," and "inappropriate use." Multiple thresholds were used to define overuse of SABA (≥3 to ≥12 canisters/y). SABA overreliance was prevalent, with approximately 20% of adults using 3 or more canisters per year (≥12 inhalations/wk). Similarly, inappropriate ICS use, classified as "suboptimal," "high use," "underuse," and "unlicensed use," was defined by varying thresholds. Specific patient populations, such as older adults, smokers, and patients with low income, were more susceptible to SABA overreliance and ICS underuse. Overreliance on SABAs was associated with increased risk of severe exacerbations, asthma-related hospitalizations, emergency department visits, and asthma-related costs. These findings emphasize the prevalence and related burden of SABA overreliance at the potential expense of appropriate ICS use.

Real-World Observational Study on the Characteristics and Treatment Patterns of Allergic Asthma Patients Receiving Omalizumab in Canada.

BACKGROUND: Omalizumab is a treatment option for pediatric and adult patients with moderate to severe allergic asthma poorly controlled with standard inhaled therapies. Clinical trials and observational studies have demonstrated the efficacy of omalizumab. There is limited real-world evidence on the characteristics and treatment patterns of Canadian asthma patients receiving omalizumab. OBJECTIVE: We profiled Canadian omalizumab users to estimate time to omalizumab discontinuation and to assess changes in concurrent medication usage before, during, and after therapy. METHODS: This was a retrospective, observational, cohort study that analyzed data from Canadian prescription claims databases. An algorithm was used to select naïve users of omalizumab with an inferred diagnosis of GINA 5-asthma who made a claim for omalizumab from February 1, 2007, to June 2, 2015. Demographic and baseline characteristics were assessed at index. Outcomes examined over the analysis period included (i) daily omalizumab dose per patient and per claim; (ii) omalizumab discontinuation (defined as ≥100-day gap in making omalizumab claims) and its potential predictors (ie, age, sex, province of residence, drug insurer; assessed by Cox Proportional Hazards Model); and (iii) for patients who discontinued omalizumab, changes in concurrent medication usage before, during, and 6 months after omalizumab usage. RESULTS: The final study cohort consisted of 1160 patients (mean age: 45.8 ± 15.2 years; 64.7% female). During the first year of omalizumab therapy, 29.5% of patients discontinued treatment. The singular characteristic that predicted omalizumab discontinuation with statistical significance was age group (20‒34 years vs 12‒19 years; hazard ratio 1.75, 95% confidence interval 1.11-2.76; P<0.05). There were significant reductions in the use of some concurrent inhaled and oral asthma medications during and/or after omalizumab use (P<0.05). CONCLUSION: Nearly one-third of patients who initiated omalizumab in Canada for refractory, moderate to severe allergic asthma discontinued treatment during the first year.