Approaches for Enhanced Extrapolation of Long-Term Survival Outcomes Using Electronic Health Records of Patients With Cancer.

OBJECTIVES: This study aimed to demonstrate enhanced survival extrapolation methods using electronic health record-derived real-world data (RWD). METHODS: The study population included patients diagnosed of ER+/HER2- metastatic breast cancer who started first-line treatment with anastrozole or letrozole between November 18, 2014, and November 18, 2015. Two patient cohorts were constructed: a clinical trial cohort from digitized MONARCH-3 clinical trial results and a RWD cohort from a deidentified electronic health record-derived database. RWD patients were weighted to trial baseline covariate distributions. Standard parametric approaches were applied to trial data and a "best-fit" model was selected. We demonstrate traditional and enhanced hybrid (pooling with weighted RWD at start, 75%, or end of trial) extrapolation approaches. RESULTS: Observed and estimated 5-year progression-free survival (PFS) rates in extrapolating the trial control arm (n = 165) were comparable across all methods. Compared with the observed 5-year mean PFS in the RWD cohort (n = 118) of 20.4 months (95% confidence interval [CI] 16.9-23.8), there was some variation among studied methods. Best-fit standard parametric model (log-normal) had 5-year mean PFS of 21.3 months (95% CI 18.2-24.9), and for the hybrid methods in order of estimate conservativeness was start of trial (20.8 months; 95% CI 18.5-23.2), 75% of trial (21.3 months; 95% CI 18.1-24.5), and end of trial (21.8 months; 95% CI 18.8-25.2). CONCLUSIONS: Our study leverages RWD to enhance long-term survival extrapolation. Future use cases should include applying patient eligibility criteria, weighting on baseline characteristics, and choice of time window to add RWD to trial data

Overuse of Health Care Services in the Management of Cancer

BackgroundOveruse, the provision of health services for which harms outweigh the benefits, results in suboptimal patient care and may contribute to the rising costs of cancer care. We performed a systematic review of the evidence on overuse in oncology.MethodsWe searched Medline, EMBASE, the Cochrane Library, Web of Science, SCOPUS databases, and 2 grey literature sources, for articles published between December 1, 2011 and March 10, 2017. We included publications from December 2011 to evaluate the literature since the inception of the ABIM Foundation's Choosing Wisely initiative in 2012. We included original research articles quantifying overuse of any medical service in patients with a cancer diagnosis when utilizing an acceptable standard to define care appropriateness, excluding studies of cancer screening. One of 4 investigator reviewed titles and abstracts and 2 of 4 reviewed each full-text article and extracted data. Methodology used PRISMA guidelines.ResultsWe identified 59 articles measuring overuse of 154 services related to imaging, procedures, and therapeutics in cancer management. The majority of studies addressed adult or geriatric patients (98%) and focused on US populations (76%); the most studied services were diagnostic imaging in low-risk prostate and breast cancer. Few studies evaluated active cancer therapeutics or interventions aimed at reducing overuse. Rates of overuse varied widely among services and among studies of the same service.ConclusionsDespite recent attention to overuse in cancer, evidence identifying areas of overuse remains limited. Broader investigation, including assessment of active cancer treatment, is critical for identifying improvement targets to optimize value in cancer care

Quality of life in long-term survivors of advanced melanoma treated with checkpoint inhibitors

BackgroundImmune checkpoint inhibitors (CIs) have revolutionized treatment of advanced melanoma, leading to an emerging population of long-term survivors. Survivors’ quality of life (QOL) and symptom burden are poorly understood. We set out to evaluate symptom burden and QOL in patients with advanced melanoma alive more than 1 year after initiating CI therapy.MethodsCross-sectional surveys, accompanied by chart review of patients with advanced melanoma treated with CIs at Memorial Sloan Kettering Cancer Center, completed therapy, and were alive >1 year after treatment initiation. Surveys were administered between February and August 2018. Surveys included: European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-Core 30, EuroQOL, items from Patient-Reported Outcomes version of the Common Terminology Criteria for Adverse Events and Fatigue Severity Scale.ResultsWe included 90 patients. The most common CI regimens were ipilimumab plus nivolumab (53%) and pembrolizumab (41%); most patients (71%) were not treated in clinical trials. Median time from CI therapy initiation was 40 months and from last dose was 28 months. Fatigue was reported by 28%, with higher fatigue scores in women than men; 12% reported difficulty sleeping. Aching joints (17%) and muscles (12%) were fairly common. Level of functioning was generally high. Overall QOL was excellent though 40% reported ‘some or moderate’ problems with anxiety/depression and 31% with pain/discomfort.ConclusionsAfter CI therapy, long-surviving advanced melanoma patients commonly report fatigue but otherwise have moderate symptom burden and good QOL. Ensuring appropriate symptom management will optimize clinical outcomes for these patients