BackgroundPatients with metastatic pancreatic cancer often have a detriment in health-related quality of life (HRQoL). In the randomized, double-blind, phase III POLO trial progression-free survival was significantly longer with maintenance olaparib, a poly(ADP-ribose) polymerase inhibitor, than placebo in patients with a germline BRCA1 and/or BRCA2 mutation (gBRCAm) and metastatic pancreatic cancer whose disease had not progressed during first-line platinum-based chemotherapy. The prespecified HRQoL evaluation is reported here.Patients and methodsPatients were randomized to receive maintenance olaparib (300 mg b.i.d.; tablets) or placebo. HRQoL was assessed using the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire Core 30-item module at baseline, every 4 weeks until disease progression, at discontinuation, and 30 days after last dose. Scores ranged from 0 to 100; a ≥10-point change or difference between arms was considered clinically meaningful. Adjusted mean change from baseline was analysed using a mixed model for repeated measures. Time to sustained clinically meaningful deterioration (TSCMD) was analysed using a log-rank test.ResultsOf 154 randomized patients, 89 of 92 olaparib-arm and 58 of 62 placebo-arm patients were included in HRQoL analyses. The adjusted mean change in Global Health Status (GHS) score from baseline was <10 points in both arms and there was no significant between-group difference [−2.47; 95% confidence interval (CI) −7.27, 2.33; P = 0.31]. Analysis of physical functioning scores showed a significant between-group difference (−4.45 points; 95% CI −8.75, −0.16; P = 0.04). There was no difference in TSCMD for olaparib versus placebo for GHS [P = 0.25; hazard ratio (HR) 0.72; 95% CI 0.41, 1.27] or physical functioning (P = 0.32; HR 1.38; 95% CI 0.73, 2.63).ConclusionsHRQoL was preserved with maintenance olaparib treatment with no clinically meaningful difference compared with placebo. These results support the observed efficacy benefit of maintenance olaparib in patients with a gBRCAm and metastatic pancreatic cancer.ClincalTrials.gov numberNCT02184195.

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.

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.

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.

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.