Plain language summary of the updated results from the CROWN study comparing lorlatinib with crizotinib in people with advanced non-small-cell lung cancer.

WHAT IS THIS SUMMARY ABOUT?: This summary shows the updated results of an ongoing research study called CROWN that was published in The Lancet Respiratory Medicine in December 2022. In the CROWN study, researchers looked at the effects of two study medicines called lorlatinib and crizotinib. The study included people with advanced non-small-cell lung cancer (NSCLC) that had not been treated previously. All people in the study had cancer cells with changes (known as alterations) in a gene called anaplastic lymphoma kinase, or ALK. This ALK gene is involved in cancer growth. In this updated study, researchers looked at the continued benefit in people who took lorlatinib compared with people who took crizotinib after 3 years. WHAT DID THIS STUDY FIND?: After 3 years of being observed, people who took lorlatinib were more likely to be alive without their cancer getting worse than people who took crizotinib. At 3 years, 64% of people who took lorlatinib were alive without their cancer getting worse compared with 19% of people who took crizotinib. The cancer was less likely to have spread within or to the brain in people who took lorlatinib than in people who took crizotinib. After 3 years of being observed, 61% of people were still taking lorlatinib and 8% of people were still taking crizotinib. People who took lorlatinib had more severe side effects than people who took crizotinib. However, these side effects were manageable. The most common side effects with lorlatinib were high levels of cholesterol or high levels of triglycerides (a type of fat) in the blood. Life-threatening side effects were seen in 13% of people who took lorlatinib and 8% in crizotinib. Two people who took lorlatinib died because of side effects from lorlatinib. WHAT DO THE RESULTS OF THE STUDY MEAN?: The updated results from the CROWN study showed that a larger percentage of people who took lorlatinib continued to benefit from their treatment after being observed for 3 years compared with those who took crizotinib.

Cost­Effectiveness of Lorlatinib in First-Line Treatment of Adult Patients with Anaplastic Lymphoma Kinase (ALK)­Positive Non­Small­Cell Lung Cancer in Sweden.

BACKGROUND: We aimed to investigate the cost effectiveness of lorlatinib, a third-generation anaplastic lymphoma kinase (ALK) tyrosine kinase inhibitor (TKI), used first-line in Sweden to treat patients with ALK-positive (ALK+) non-small cell lung cancer (NSCLC). In January 2022, the European Medicines Agency (EMA) extended its approval of lorlatinib to include adult patients with ALK+ NSCLC not previously treated with an ALK inhibitor. Extended first-line approval was based on results from CROWN, a phase III randomized trial that enlisted 296 patients randomized 1:1 to receive lorlatinib or crizotinib. Our analysis compared lorlatinib against the first-generation ALK-TKI crizotinib, and second-generation ALK TKIs alectinib and brigatinib. METHODS: A partitioned survival model with four health states [pre-progression, non-intracranial (non-central nervous system [CNS]) progression, CNS progression, and death] was constructed. The progressed disease state (which is typically modelled in cost-effectiveness analyses of oncology treatments) was explicitly separated into non-CNS and CNS progression as brain metastases, which are common in NSCLC, and can have a large impact on patient prognosis and health-related quality of life. Treatment effectiveness estimates in the lorlatinib and crizotinib arms of the model were derived from CROWN data, while indirect relative effectiveness estimates for alectinib and brigatinib were informed using network meta-analysis (NMA). Utility data were derived from the CROWN study in the base case, and cost-effectiveness results were compared when applying UK and Swedish value sets. Costs were obtained from Swedish national data. Deterministic and probabilistic sensitivity analyses were conducted to test model robustness. RESULTS: Fully incremental analysis identified crizotinib as the least costly and least effective treatment. Brigatinib was extendedly dominated by alectinib and, subsequently, alectinib was extendedly dominated by lorlatinib. Lorlatinib was associated with an incremental cost-effectiveness ratio (ICER) of Swedish Krona (SEK) 613,032 per quality-adjusted life-year (QALY) gained compared with crizotinib. Probabilistic results were generally consistent with deterministic results, and one-way sensitivity identified NMA HRs, alectinib and brigatinib treatment duration, and the CNS-progressed utility multiplier as key model drivers. CONCLUSIONS: The ICER of SEK613,032 for lorlatinib versus crizotinib falls below the typical willingness-to-pay threshold per QALY gained for high-severity diseases in Sweden (approximately SEK1,000,000). Furthermore, as brigatinib and alectinib were extendedly dominated in the incremental analysis, the results of our study indicate that lorlatinib may be considered a cost-effective treatment option for first-line patients with ALK+ NSCLC in Sweden when compared with crizotinib, alectinib, and brigatinib. Longer-term follow-up data for endpoints informing treatment effectiveness for all first-line treatments would help to reduce uncertainty in the findings.

Real-world study of next-generation sequencing diagnostic biomarker testing for patients with lung cancer in Japan.

Our previous real-world studies raised concerns that sequential biomarker testing may lead to increased time to treatment when compared with simultaneous single biomarker testing. The Oncomine Dx target test (ODxTT), a next-generation sequencing-based multiplex biomarker panel test approved in Japan in 2019, is expected to improve time to treatment due to changes in testing methods. This retrospective observational study examined data claims for reimbursement submitted for patients with lung cancer in Japan between June 1, 2019, and March 31, 2020. To evaluate the change in testing prevalence over time and associated improvements in time to treatment, descriptive statistics were used to characterize biomarker testing patterns and rates and evaluate the time to treatment in the time following the approval of ODxTT considering transitions over time during the evaluation period. EGFR and programmed death ligand 1 (PD-L1) were the most tested biomarkers in overall single and simultaneous single testing in the 6177 patients in this study. Individual single biomarker testing gradually decreased over time, except testing for PD-L1, which remained constant. The use of ODxTT gradually increased in this period. Time to treatment decreased from 29 to 22 days with ODxTT, in contrast to single biomarker tests (median 21-23 days overall). These results indicate that biomarker testing frequency changed in Japanese clinical practice during the study and that the use of ODxTT has increased over time, which potentially contributed to the shortening of time to treatment.

Matching-Adjusted Indirect Comparisons of Lorlatinib Versus Chemotherapy for Patients With Second-Line or Later Anaplastic Lymphoma Kinase-Positive Non-Small Cell Lung Cancer.

OBJECTIVES: This study aimed to compare the relative efficacy of lorlatinib, an anaplastic lymphoma kinase-tyrosine kinase inhibitor, with chemotherapy, for patients with second-line or later advanced anaplastic lymphoma kinase-positive non-small cell lung cancer. The endpoints of interest were overall survival (OS) and progression-free survival (PFS). METHODS: Evidence for lorlatinib was informed by the single-arm phase I/II trial B7461001. A systematic literature review (SLR) was performed to identify OS and PFS data for chemotherapy. Unanchored matching-adjusted indirect comparisons (MAICs) between lorlatinib and chemotherapy (pemetrexed/docetaxel, platinum-based, or systemic therapy) were performed. RESULTS: The SLR identified 3 relevant studies reporting PFS. Lorlatinib was associated with a significant decrease in the hazard of progression versus the 2 types of chemotherapy assessed. For PFS, the MAIC of lorlatinib versus the combined treatment arm of docetaxel or pemetrexed resulted in an adjusted hazard ratio (HR) of 0.22 (95% confidence interval [CI] 0.15-0.31). When lorlatinib was compared with platinum-based chemotherapy through an MAIC, the adjusted HR for PFS was 0.40 (95% CI 0.29-0.55). An exploratory comparison was performed for OS with evidence for systemic therapy (assumed equivalent to chemotherapy) not identified in the SLR. Lorlatinib provided a significant decrease in hazard of death (OS) versus systemic therapy, with HRs ranging from 0.12 (95% CI 0.05-0.27) to 0.43 (95% CI 0.27-0.60). CONCLUSIONS: Lorlatinib demonstrated a significant improvement in PFS compared with chemotherapy, although limitations in the analyses were identified. The evidence informing OS comparisons was highly limited but suggested benefit of lorlatinib compared with systemic therapy.

Efficacy and safety of first-line lorlatinib versus crizotinib in patients with advanced, ALK-positive non-small-cell lung cancer: updated analysis of data from the phase 3, randomised, open-label CROWN study.

BACKGROUND: After a median follow-up of 18·3 months, the third-generation anaplastic lymphoma kinase (ALK) tyrosine-kinase inhibitor, lorlatinib, improved progression-free survival in patients with treatment-naive, ALK-positive non-small-cell lung cancer in the phase 3 CROWN study. Here we report updated efficacy data, including intracranial activity, from an unplanned analysis after 3 years of follow-up. METHODS: CROWN is an ongoing, international, randomised, open-label phase 3 trial done in 104 centres in 23 countries worldwide. Eligible participants were aged 18 years and older or aged 20 years and older (depending on local regulations) with advanced, ALK-positive non-small-cell lung cancer, had received no previous systemic treatment for metastatic disease, had at least one extracranial measurable target lesion (according to the Response Evaluation Criteria in Solid Tumours [RECIST], version 1.1), and had an Eastern Cooperative Oncology Group performance status score of 0-2. Patients were randomly assigned (1:1) to oral lorlatinib 100 mg daily or oral crizotinib 250 mg twice daily in 28-day cycles. Randomisation was stratified by the presence or absence of brain metastasis, and by ethnicity. Since the primary endpoint of the study had been met at the planned interim analysis, no further formal analysis of progression-free survival was planned, per protocol. The current unplanned analysis was done to further characterise tumour-related endpoints with a longer follow-up and is presented descriptively. For the planned study, the primary endpoint was progression-free survival assessed by blinded independent central review. Secondary endpoints included progression-free survival (investigator), objective response rate, intracranial objective response rate, time to intracranial progression, duration of response, intracranial duration of response, and safety. Efficacy endpoints were also assessed by the presence or absence of baseline brain metastases. This study is registered with ClinicalTrials.gov, NCT03052608. FINDINGS: Between May 11, 2017, and Feb 28, 2019, 425 patients were screened for eligibility, of whom 296 were enrolled and randomly assigned to the lorlatinib (n=149) or crizotinib (n=147) group. At data cutoff for this unplanned analysis (Sept 20, 2021), median duration of follow-up for progression-free survival was 36·7 months (IQR 31·3-41·9) for lorlatinib and 29·3 months (10·8-35·0) for crizotinib. Median progression-free survival by blinded independent central review was not reached (95% CI not reached-not reached) for lorlatinib and was 9·3 months (7·6-11·1) for crizotinib (hazard ratio [HR] 0·27 [95% CI 0·18-0·39]). 3-year progression-free survival was 64% (95% CI 55-71) in the lorlatinib group and 19% (12-27) in the crizotinib group. Progression-free survival (investigator), objective response rate, intracranial objective response rate, time to intracranial progression, and duration of response were improved with lorlatinib versus crizotinib. In patients with baseline brain metastases (n=37 lorlatinib; n=39 crizotinib), the HR for time to intracranial progression for lorlatinib versus crizotinib was 0·10 (95% CI 0·04-0·27); in patients without baseline brain metastases (n=112 lorlatinib; n=108 crizotinib), the HR was 0·02 (95% CI 0·002-0·14). In patients without brain metastases, one (1%) in the lorlatinib group and 25 (23%) in the crizotinib group had intracranial progression. Grade 3-4 adverse events occurred in 113 (76%) of 149 patients (most commonly due to altered lipid levels) with lorlatinib and in 81 (57%) of 142 patients with crizotinib. Adverse events led to treatment discontinuation in 11 (7%) patients in the lorlatinib group and 14 (10%) patients in the crizotinib group. There were no new safety signals. INTERPRETATION: These updated, long-term data from CROWN show the durable benefit of lorlatinib over crizotinib in patients with treatment-naive, ALK-positive non-small-cell lung cancer and support the use of first-line lorlatinib in patients with and without baseline brain metastases. FUNDING: Pfizer.

Patient-reported outcomes from the randomized phase 3 CROWN study of first-line lorlatinib versus crizotinib in advanced ALK-positive non-small cell lung cancer.

OBJECTIVES: Quality of life (QoL) for patients with non-small cell lung cancer (NSCLC) is negatively impacted by their disease and treatment side effects. We present detailed patient-reported outcome (PRO) data from the phase 3 CROWN study, which compared lorlatinib with crizotinib in patients with previously untreated ALK-positive advanced NSCLC. MATERIALS AND METHODS: PROs were assessed using the European Organisation for Research and Treatment of Cancer QoL Questionnaire with Lung Cancer module. A longitudinal, random-intercept, random-slope, mixed-effect model assessed score changes from baseline up to (not including) end of treatment. Mean changes of absolute scores from baseline at each cycle were calculated and presented up to cycle 18 (≥ 10-point change considered clinically meaningful). RESULTS: In both lorlatinib (n = 148) and crizotinib (n = 140) arms, there were longitudinal improvements across multiple functioning and symptom scores during treatment compared with pre-treatment. Numerical improvements for most longitudinal functioning scores (physical, role, emotional, social) favored lorlatinib; cognitive functioning favored crizotinib. Numerical improvements favored lorlatinib for several symptoms (fatigue, nausea and vomiting, insomnia, appetite loss, constipation, diarrhea [clinically meaningful improvement], and cough); peripheral neuropathy favored crizotinib. Subgroup analyses showed PROs did not differ by presence/absence of baseline brain metastases. CONCLUSIONS: Patients receiving first-line lorlatinib or crizotinib showed improvements and delayed deterioration in QoL, functioning, and several symptoms. Alongside the previously reported significantly longer progression-free survival and higher intracranial response rates for lorlatinib versus crizotinib, these data further support the use of lorlatinib over crizotinib in patients with advanced ALK-positive NSCLC with/without baseline brain metastases and provide evidence of several QoL improvements with lorlatinib when used in the first-line setting.

Final Overall Survival, Safety, and Quality of Life Results From a Phase 2 Study of Crizotinib in East Asian Patients With ROS1-Positive Advanced NSCLC.

Introduction: Crizotinib provided meaningful clinical benefit in the initial analysis of a phase 2 study in East Asian patients with advanced ROS1-positive NSCLC (NCT01945021). Nevertheless, overall survival (OS) data were immature. Here, we present the final OS, quality of life (QoL), and safety data after an additional 3 years of follow-up. Methods: In this phase 2, open-label, single-arm trial, East Asian patients with ROS1-positive advanced NSCLC who had received less than or equal to three systemic therapies previously were treated with crizotinib 250 mg twice daily on a continuous daily dosing schedule in 28-day cycles. The OS (secondary end point) was analyzed for the total population, by country, and by number of previous chemotherapy regimens. QoL and safety were also evaluated. Results: With a median duration of follow-up of 56.1 months, the median OS was 44.2 months (95% confidence interval: 32.0-not reached) for the total population (N = 127). Differences in median OS were observed among individual countries and with number of previous regimens. The improvement in QoL found in the previous analysis was maintained with the extended follow-up. Treatment-related adverse events led to crizotinib dose reductions or permanent treatment discontinuations in 17.3% and 2.4%, respectively, of the patients. Conclusions: This is the largest trial of an ALK/ROS1 inhibitor to treat patients with ROS1-positive advanced NSCLC and provides a new benchmark for OS in East Asian patients. The QoL and safety profile with long-term follow-up were consistent with previous reports and support the continued use of crizotinib in the treatment of patients with ROS1-positive advanced NSCLC.

Effectiveness of crizotinib versus entrectinib in ROS1-positive non-small-cell lung cancer using clinical and real-world data.

Aims: To compare clinical trial results for crizotinib and entrectinib in ROS1-positive non-small-cell lung cancer and compare clinical trial data and real-world outcomes for crizotinib. Patients & methods: We analyzed four phase I-II studies using a simulated treatment comparison (STC). A STC of clinical trial versus real-world evidence compared crizotinib clinical data to real-world outcomes. Results: Adjusted STC found nonsignificant trends favoring crizotinib over entrectinib: objective response rate, risk ratio = 1.04 (95% CI: 0.85-1.28); median duration of response, mean difference = 16.11 months (95% CI: -1.57- 33.69); median progression-free survival, mean difference = 3.99 months (95% CI: -6.27-14.25); 12-month overall survival, risk ratio = 1.01 (95% CI: 0.90-1.12). Nonsignificant differences were observed between the trial end point values and the real-world evidence for crizotinib. Conclusions: Crizotinib and entrectinib have comparable efficacy in ROS1-positive non-small-cell lung cancer.

Real-World Outcomes Among Crizotinib-Treated Patients with ROS1-Positive Advanced Non-Small-Cell Lung Cancer: A Community Oncology-Based Observational Study.

BACKGROUND: Crizotinib was the first oral targeted therapy approved by the US Food and Drug Administration (FDA), on 11 March 2016, for c-ros oncogene 1 (ROS1)-positive advanced non-small-cell lung cancer (NSCLC). Data to support long-term clinical benefit in a real-world setting are limited. OBJECTIVE: This study aimed to assess real-world clinical outcomes among patients with ROS1-positive advanced NSCLC treated with crizotinib in the US community oncology setting. PATIENTS AND METHODS: We conducted a retrospective cohort study using iKnowMed electronic health record data to identify adult patients with ROS1-positive advanced NSCLC who initiated crizotinib between 17 January 2013 (time of the addition of crizotinib for ROS1-positive NSCLC to National Comprehensive Cancer Network (NCCN) treatment guidelines) and 1 June 2019 with a potential follow-up period through 1 December 2019. Patient characteristics were assessed descriptively. Kaplan-Meier analyses were used to evaluate time to treatment discontinuation (TTD), time to next treatment (TTNT), and overall survival (OS). A Cox proportional hazards model was conducted to determine factors associated with OS. RESULTS: The study cohort included 38 ROS1-positive patients treated with crizotinib. The median age was 68 years (interquartile range 60.0-73.0) and 65.8% were female. Over 50% were current/former smokers, and 18.4% had an Eastern Cooperative Oncology Group (ECOG) performance status of 2. Overall, 21 (55.3%) patients remained on crizotinib, 10 (26.3%) had evidence of subsequent treatment, and 16 (42.1%) died. The median TTD, TTNT, and OS were 25.2 months [95% confidence interval (CI): 5.2-not reached (NR)], 25.0 months (95% CI 5.2-61.0), and 36.2 months (95% CI 15.9-NR), respectively. In a multivariate Cox regression model, ECOG performance status of 2 was associated with a 4.9-fold higher risk of death (hazard ratio = 4.9; 95% CI 1.1-21.4) compared to ECOG performance status of 0 or 1. CONCLUSIONS: This ROS1-positive NSCLC real-world population was older and had a higher proportion of smokers and of patients with poorer ECOG performance status than those investigated in clinical trials. Nevertheless, our findings support the clinical benefit of crizotinib in this patient population with ROS1-positive advanced NSCLC.

Real-World Evidence of Diagnostic Testing for Driver Oncogene Mutations in Lung Cancer in Japan.

INTRODUCTION: Diagnostic testing is important in determining appropriate treatment for individuals with lung cancer. In 2018, testing of five biomarkers (EGFR, ALK, ROS1, BRAF, programmed cell death-ligand 1 [PD-L1]) was approved in Japan. Information is lacking regarding real-world testing patterns. METHODS: This descriptive, retrospective observational study used the Japan Medical Data Vision Co., Ltd. (MDV), database (June 2017-November 2018) and covered data for EGFR, ALK, ROS1, and PD-L1; records on BRAF testing were not yet available. Adults diagnosed with having lung cancer (International Classification of Diseases-10 C34) with record of any biomarker test ordered were included. RESULTS: Of 8323 patients with any biomarker test, 83.2% were tested for EGFR, 55.3% for ALK, 32.2% ROS1, and 77.2% PD-L1. Combinations of EGFR with other biomarkers accounted for approximately 80% of the testing patterns; 1427 patients (17.1%) had combination testing ordered for EGFR/ALK/ROS1/PD-L1, but some biomarker combinations were tested in less than 1% of the cases. Median time from first testing order to treatment order was 22 (range: 2-525) days overall and increased with number of testing instances: 21 (2-509) days for patients with one, 28 (3-525) days for patients with two, and 30 (9-502) days for patients with three. A 7-day pattern of peaks was observed in the test order date and time to treatment. CONCLUSIONS: This real-world evidence revealed variations in diagnostic testing patterns, which could affect time to treatment in Japan. Variations are likely influenced by individual biomarker prioritization considering limited tissue samples in clinical practice.

Reliability, validity and important difference estimates for the NCCN-FACT Ovarian Symptom Index-18 (NFOSI-18).

Objective: To evaluate psychometric performance of the NCCN-FACT Ovarian Cancer Symptom Index-18 (NFOSI-18) in advanced ovarian cancer. Methods: Cross-sectional, observational data from patients receiving treatment for ovarian cancer. Other measures included European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire core (EORTC QLQ-C30) and associated ovarian cancer module (EORTC QLQ-OV28) and Work Productivity and Activity Impairment. Internal consistency reliability, construct validity and anchor-based clinically important differences were assessed. Results: 897 patients were analyzed. Reliability was acceptable for all NFOSI-18 scores; construct validity was supported. Twelve anchors sufficiently correlated with NFOSI-18 scores and suggested clinically important differences: NFOSI-18 total score (5-7), disease-related symptoms - physical (3-4), disease-related symptoms - emotional (1), treatment side effects (2) and functional well-being (1-2). Conclusions: Results provide evidence of reliability and validity of NFOSI-18 scores. Generated CIDs will help improve interpretation of between-group treatment differences in clinical trials.

Lay abstract The National Comprehensive Cancer Network Functional Assessment of Cancer Therapy ­ Ovarian Cancer Symptom Index-18 (NFOSI-18) is a questionnaire assessing the health of patients with ovarian cancer. When using such questionnaires, it is important to evidence that they produce consistent scores (referred to as reliability) and are aligned with other assessments of health (referred to as construct validity). It is also important to set guidelines on what constitutes a clinically important difference in scores, so clinicians and researchers can judge how effective new treatments are. This study analyzed data from 897 patients with advanced ovarian cancer, providing evidence of reliability and construct validity. Guidelines for clinically important differences were also provided. The findings support continued use of the NFOSI-18.

The Cost-Effectiveness of Lorlatinib Versus Chemotherapy as a Second- or Third-Line Treatment in Anaplastic Lymphoma Kinase (ALK)-Positive Non-small-cell Lung Cancer in Sweden.

BACKGROUND: Lorlatinib is a third-generation anaplastic lymphoma kinase (ALK)/c-ros oncogene 1 (ROS1) tyrosine kinase inhibitor (TKI) with efficacy in patients with ALK-rearranged non-small-cell lung cancer (NSCLC) previously treated with a second-generation ALK inhibitor or with first- and second-generation ALK inhibitors. We examined the cost-effectiveness of second- or third-line+ (2L+ or 3L+) lorlatinib in Sweden, versus chemotherapy. METHODS: A partitioned survival model with three health states (progression free, progressed, or death) was used. Lorlatinib relative efficacy versus chemotherapy was derived using unanchored matching adjusted indirect treatment comparisons from a phase 2 clinical trial. Utility data were derived from the same trial and published studies. Costs (year 2019) were obtained from Swedish national data. Costs and benefits were discounted at 3% per annum using a societal perspective (base case). Model robustness was evaluated with deterministic and probabilistic sensitivity analyses. RESULTS: For 2L+, the average discounted total quality-adjusted life year (QALY) gain was 1.29 years. Total incremental costs were Swedish krona (SEK) 731,791, resulting in an incremental cost-effectiveness ratio (ICER) of SEK 566,278 per QALY gained. Non-discounted survival gain amounted to 1.94 years. For 3L+, the average discounted total QALY gain was 1.25 years. Total incremental costs were SEK 754,801, resulting in an ICER of SEK 603,934 per QALY gained. Non-discounted survival gain was 1.88 years. Sensitivity analyses were consistent. CONCLUSIONS: ICERs ranged from SEK 421,000 to SEK 384,066 less than the boundary for a cost-effective treatment for a high-severity disease in Sweden (SEK 988,000), suggesting 2L+ or 3L+ lorlatinib is a cost-effective treatment for ALK-positive NSCLC versus chemotherapy.

The burden of selected cancers in the US: health behaviors and health care resource utilization.

OBJECTIVE: To characterize the disease burden among survivors of those cancers having the highest incidence in the US. METHODS: Adult (≥18 years) survivors of the 11 most frequently diagnosed cancers were identified from publically available data sources, including the Surveillance Epidemiology and End Results 9 1973-2012, National Health Interview Survey 2013, and the Medical Expenditure Panel Survey 2011. Chi-square tests and one-way analyses of variance were utilized to assess differences between cancer survivors and non-cancer controls in behavioral characteristics, symptoms and functions, preventative screenings, and health care costs. RESULTS: Hematologic malignancies, melanoma, and breast, prostate, lung, colon/rectal, bladder, kidney/renal, uterine, thyroid, and pancreatic cancers had the highest incidence rates. Breast cancer had the highest incidence among women (156.4 per 100,000) and prostate cancer among men (167.2 per 100,000). The presence of pain (P=0.0003), fatigue (P=0.0005), and sadness (P=0.0012) was consistently higher in cancer survivors 40-64 years old vs. non-cancer controls. Cancer survivors ≥65 years old had higher rates of any functional limitations (P=0.0039) and reported a lack of exercise (P<0.0001) compared with the non-cancer controls. However, obesity rates were similar between cancer survivors and non-cancer controls. Among cancer survivors, an estimated 13.5 million spent $169.4 billion a year on treatment, with the highest direct expenditures for breast cancer ($39 billion), prostate cancer ($37 billion), and hematologic malignancies ($25 billion). Prescription medications and office-based visits contributed equally as the cost drivers of direct medical spending for breast cancer, while inpatient hospitalization was the driver for prostate (52.8%) and lung (38.6%) cancers. CONCLUSION: Understanding the resource utilization implications, health, and well-being of cancer survivors can inform approaches to interventions for improving long-term care.

The burden of family caregiving in the United States: work productivity, health care resource utilization, and mental health among employed adults.

BACKGROUND: Family caregiving is an increasingly important component of care for patients and the elderly. OBJECTIVE: The aim of this study is to characterize the burden of family caregiving among employed adults. METHODS: Employed adults (≥18 years) from the 2013 US National Health and Wellness Survey (NHWS) were classified as family caregivers if they reported currently caring for at least one adult relative. Chi-square tests and one-way analyses of variance assessed whether employed caregivers, weighted to the US population, differed from employed non-caregivers on behavioral characteristics, workplace productivity, and health care resource utilization. RESULTS: Eight million workers were family caregivers in the United States, more often female than male (51% vs. 49%, P < 0.05), and 53% were between 40 and 64 years of age. Eighteen percent of caregivers were Hispanic compared with 15% of non-caregivers (P < 0.05). Similar behavioral characteristics between caregivers and non-caregivers included daily alcohol consumption (6% vs. 5%) and lack of vigorous exercise (25% vs. 29%), but caregivers had a higher prevalence of smoking (26% vs. 19%, P < 0.05). Caregivers reported a higher mean percentage of work time missed (8% vs. 4%, P < 0.05) and greater productivity impairment (24% vs. 14%, P < 0.05). Some form of depression was reported by 53% of caregivers compared with 32% of non-caregivers (P < 0.05), and more caregivers had self-reported insomnia than non-caregivers (46% vs. 37%, P < 0.05). The number of self-reported diagnosed comorbidities was higher among caregivers compared with that of non-caregivers (5.0 vs. 3.1, P < 0.05), as was the mean number of outpatient visits in the previous 6 months (4.1 vs. 2.7, P < 0.05). CONCLUSION: Family caregiving is associated with a multidimensional burden that impacts caregivers and has implications for employers and the health care system. Clinicians and employers need to recognize and understand this burden. Characterization of caregivers as reported in this study can inform development of targeted programs to help mitigate the burden.