Real-world study on the characteristics, post-nephrectomy journey, and outcomes of patients with early-stage renal cell carcinoma based on risk groups.

OBJECTIVES: To examine real-world characteristics, journey, and outcomes among patients with locoregional, nonmetastatic renal cell carcinoma (RCC). METHODS: A retrospective analysis of medical records from the ConcertAI Oncology Dataset was performed on adults in the United States with newly diagnosed nonmetastatic RCC between January 2012-December 2017 who received surgical treatment, and were followed until August 2021. Patients were stratified based on the risk of recurrence after nephrectomy. Recurrence rate and survival outcomes were assessed. RESULTS: The cohort (n = 439) had a median age of 64 years, 66.1% were male, and 76.5% had clear-cell histology. The median follow-up time from nephrectomy was 39.3 months overall, 41.0 months for intermediate-high-risk patients (n = 377; 85.9%) and 24.1 months for high-risk patients (n = 62; 14.1%). For intermediate-high- and high-risk patients, respectively, 68.4% and 56.5% had ≥1 medical oncologist visit after nephrectomy. Of 260 patients with documentation of postoperative imaging assessments, 72% were ordered by medical oncologists, and the median time from initial nephrectomy to the first scan was 110 days (intermediate-high-risk) and 51 days (high-risk). Provider-documented recurrence occurred in 223 (50.8%) patients, of whom 41.7% had ≥1 medical oncologist visit before the recurrence. Three-year disease-free survival (DFS), and overall survival rates were 49.4% and 80.8% (all patients): 27.7% and 64.7% (high-risk); and 52.9% and 83.3% (intermediate-high-risk). CONCLUSIONS: Our study reports low DFS after nephrectomy for patients with intermediate-high- and high-risk RCC. Subsequent approval and use of new and newly approved adjuvant therapeutic options could potentially delay or prevent recurrence.

Patient-Reported Outcomes in KEYNOTE-564: Adjuvant Pembrolizumab Versus Placebo for Renal Cell Carcinoma.

BACKGROUND: In patients with renal cell carcinoma (RCC) enrolled in the phase III KEYNOTE-564 trial (NCT03142334), disease-free survival (DFS) following nephrectomy was prolonged with use of adjuvant pembrolizumab therapy versus placebo. Patient-reported outcomes (PROs) provide an important measure of health-related quality of life (HRQoL) and can complement efficacy and safety results. PATIENTS AND METHODS: In KEYNOTE-564, 994 patients were randomly assigned to receive pembrolizumab 200 mg (n = 496) or placebo (n = 498) intravenously every 3 weeks for ≤17 cycles. Patients who received ≥1 dose of treatment and completed ≥1 HRQoL assessment were included in this analysis. HRQoL end points were assessed using the EORTC QLQ-C30, FKSI-DRS, and EQ VAS. Prespecified and exploratory PRO end points were mean change from baseline in EORTC QLQ-C30 GHS/QoL score, EORTC QLQ-C30 physical function subscale score, and FKSI-DRS score. RESULTS: No clinically meaningful difference in least squares mean scores for pembrolizumab versus placebo were observed at week 52 for EORTC QLQ-C30 GHS/QoL (-2.5; 95% CI -5.2 to 0.1), EORTC QLQ-C30 physical functioning (-0.87; 95% CI -2.7 to 1.0), and FKSI-DRS (-0.7; 95% CI -1.2 to -0.1). Most PRO scores remained stable or improved for the EORTC QLQ-C30 GHS/QoL (pembrolizumab, 54.3%; placebo, 67.5%), EORTC QLQ-C30 physical functioning (pembrolizumab, 64.7%; placebo, 68.8%), and FKSI-DRS (pembrolizumab, 58.2%; placebo, 66.3%). CONCLUSIONS: Adjuvant treatment with pembrolizumab did not result in deterioration of HRQoL. These findings together with the safety and efficacy findings support adjuvant pembrolizumab treatment following nephrectomy. TRIAL REGISTRATION: Clinicaltrials.gov Identifier: NCT03142334.

Cost-Effectiveness Analysis of Pembrolizumab as an Adjuvant Treatment of Renal Cell Carcinoma Post-nephrectomy in the United States.

INTRODUCTION: Pembrolizumab was recently approved as an adjuvant treatment of renal cell carcinoma (RCC), based on prolonged disease-free survival compared to placebo in the phase III KEYNOTE-564 trial. The objective of this study was to evaluate the cost-effectiveness of pembrolizumab as monotherapy in the adjuvant treatment of RCC post-nephrectomy, from a US health sector perspective. PATIENTS AND METHODS: A Markov model with 4 health states (disease-free, locoregional recurrence, distant metastases, and death) was developed to compare the cost and effectiveness of pembrolizumab versus routine surveillance or sunitinib. Transition probabilities were estimated using patient-level KEYNOTE-564 data (cutoff: June 14, 2021), a retrospective study, and published literature. Costs of adjuvant and subsequent treatments, adverse events, disease management, and terminal care were estimated in 2022 US$. Utilities were based on EQ-5D-5L data collected in KEYNOTE-564. Outcomes included costs, life-years (LYs), and quality-adjusted LYs (QALYs). Robustness was assessed through one-way and probabilistic sensitivity analyses. RESULTS: Total cost per patient was $549,353 for pembrolizumab, $505,094 for routine surveillance, and $602,065 for sunitinib. Over a lifetime, pembrolizumab provided gains of 0.96 QALYs (1.00 LYs) compared to routine surveillance, yielding an incremental cost-effectiveness ratio of $46,327/QALY. Pembrolizumab dominated sunitinib with 0.89 QALYs (0.91 LYs) gained while saving costs. At a $150,000/QALY threshold, pembrolizumab was cost-effective versus both routine surveillance and sunitinib in 84.2% of probabilistic simulations. CONCLUSION: Pembrolizumab is projected to be cost-effective as an adjuvant RCC treatment versus routine surveillance or sunitinib based on a typical willingness-to-pay threshold.

Disease-free survival as a predictor of overall survival in localized renal cell carcinoma following initial nephrectomy: A retrospective analysis of Surveillance, Epidemiology and End Results-Medicare datac.

OBJECTIVES: This study aimed to assess whether disease-free survival (DFS) may serve as a predictor for long-term survival among patients with intermediate-high risk or high risk renal cell carcinoma (RCC) post-nephrectomy when overall survival (OS) is unavailable. METHODS: The Surveillance, Epidemiology and End Results-Medicare database (2007-2016) was used to identify patients with non-metastatic intermediate-high risk and high risk RCC post-nephrectomy. Landmark analysis and Kendall's τ were used to evaluate the correlation between DFS and OS. Multivariable regression models were used to quantify the incremental OS post-nephrectomy associated with increased time to recurrence among patients with recurrence, adjusting for baseline covariates. RESULTS: A total of 643 patients were analyzed; mean age of 75 years; >95% of patients had intermediate-high risk RCC at diagnosis; 269 patients had recurrence post-nephrectomy. For patients with versus without recurrence at the landmark points of 1, 3, and 5 years post-nephrectomy, the 5-year OS were 37.0% versus 70.1%, 42.3% versus 72.8%, and 53.2% versus 78.6%, respectively. The Kendall's τ between DFS and OS post-nephrectomy was 0.70 (95% CI: 0.65, 0.74; p < 0.001). After adjusting for baseline covariates, patients with one additional year of time to recurrence were associated with 0.73 years longer OS post-nephrectomy (95% CI: 0.40, 1.05; p < 0.001). CONCLUSION: The significant positive association of DFS and OS among patients with intermediate-high risk and high risk RCC post-nephrectomy from this study supports the use of DFS as a potential predictor of OS for these patients when OS data are immature.

Clinical and economic burdens of recurrence following nephrectomy for intermediate high- or high-risk renal cell carcinoma: A retrospective analysis of Surveillance, Epidemiology, and End Results-Medicare data.

BACKGROUND: Renal cell carcinoma (RCC) is associated with a high risk of recurrence. Although RCC has been shown to impose a substantial burden on patients, little is known about the incremental clinical and economic burden attributable to disease recurrence. With recent advances in the RCC-therapeutic landscape, including adjuvant therapies, it is important to quantify the clinical and economic burden associated with RCC recurrence to better evaluate the potential impact of treatment in this patient population. OBJECTIVE: To quantify the incremental clinical and economic burden associated with disease recurrence among patients with intermediate high-risk and high-risk RCC postnephrectomy. METHODS: Data from the Surveillance, Epidemiology, and End Results-Medicare database (2007-2016) were used to identify patients with newly diagnosed, intermediate high-risk or high-risk RCC following nephrectomy. Patients with a diagnosis of metastatic disease or repeat nephrectomy or initiating a systemic treatment for advanced RCC were grouped as the recurrence cohort; patients without evidence of recurrence were grouped as the cohort without recurrence. Health care resource utilization (HRU), health care costs (2019 US dollars), and overall survival (OS) were compared between cohorts with and without recurrence, adjusting for demographic and clinical characteristics. RESULTS: A total of 269 patients with recurrence and 374 patients without recurrence were analyzed. Mean age was 75.2 and 75.7 years (P = 0.383), respectively, and 64.7% and 57.8% (P = 0.076) of patients were male, respectively. Median follow-up duration was 17 and 28 months, respectively. Patients with recurrence had a significantly shorter OS relative to patients without recurrence (adjusted hazard ratio = 6.00; 95% CI = 4.24-8.48; P < 0.001). Additionally, compared with patients without recurrence, patients with recurrence had significantly more inpatient admissions (0.16 vs 0.04 admissions per person-month [PM]; adjusted incidence rate ratio [aIRR] = 3.88; 95% CI = 3.12-4.81), outpatient visits (3.06 vs 1.77 visits per PM; aIRR = 1.68; 95% CI = 1.56-1.81), emergency department visits (0.10 vs 0.05 visits per PM; aIRR = 2.11; 95% CI = 1.66-2.68), and days hospitalized (1.40 vs 0.35 days per PM; aIRR = 6.73; 95% CI = 4.95-9.15) per patient per month (all P < 0.001). Adjusted mean monthly health care costs per patient were significantly higher among patients with recurrence vs patients without recurrence (differences of all-cause total costs, total medical costs, and pharmacy cost per month: $6,320, $4,924, and $1,387; all P < 0.001). CONCLUSIONS: RCC recurrence is associated with a significant increase in mortality, HRU, and health care costs, highlighting the substantial unmet need in patients with intermediate high-risk and high-risk RCC postnephrectomy when adjuvant therapies are not widely available. DISCLOSURES: Dr Sundaram is an employee of Merck Sharp & Dohme LLC., a subsidiary of Merck & Co., Inc., and holds stock in AbbVie, Abbott, Johnson & Johnson, Bristol Myers Squibb, and Merck & Co., Inc. Dr Bhattacharya is an employee of Merck Sharp & Dohme LLC., a subsidiary of Merck & Co., Inc., and holds stock in Merck & Co., Inc. Dr Adejoro and Dr Rogerio were employees of Merck Sharp & Dohme LLC., a subsidiary of Merck & Co., Inc. at the time of study conduct. Dr Adejoro holds stock in Johnson & Johnson. Dr Song, Dr Zhang, Mr Carley, and Dr Signorovitch are employees of Analysis Group, Inc., a consulting firm that received funding from Merck & Co., Inc. for the conduct of this research. Ms Zhu was an employee of Analysis Group, Inc. at the time of study conduct. Dr Haas is a Professor of Medicine at the Perelman School of Medicine, University of Pennsylvania and also serves on the advisory board for Aveo, Calithera and Exelixis, Co. Financial support for this study was provided by Merck & Co., Inc. The study sponsor was involved in the design and conduct of the study; collection, management, analysis, interpretation of data; preparation, review, or approval of the manuscript; and decision to submit the manuscript for publication.

Comparing Medical Utilization and Cost Outcomes in Oral Versus Injectable Immunotherapy Users with Chronic Inflammatory Joint and Skin Diseases.

BACKGROUND: Rheumatoid arthritis (RA), psoriatic arthritis (PsA), and psoriasis (PSO) are immune-mediated systemic, chronic inflammatory conditions. Moderate to severe disease is treated with conventional disease-modifying antirheumatic drugs (DMARDs) such as methotrexate, sulfasalazine, or leflunomide. If a patient does not respond to these firstline treatments, then tumor necrosis factor inhibitor (TNFi) or non-TNFi immunotherapy agents are administered via infusion, injection, or taken orally. Although the effectiveness of established infusion, injection, and newer oral therapies are known, the relative effectiveness among the routes of administration is not well understood. OBJECTIVE: To compare drug use, health care resource utilization, and costs among patients who are treatment-naive to oral immunotherapy and injectable biologic immunotherapy. METHODS: This retrospective observational study used claims data from a large U.S. health plan to identify new users of oral and injectable immunotherapy, diagnosed with a joint (RA or PsA), skin (PSO), or joint and skin condition from July 1, 2014, to June 30, 2017. The index date was the first claim for an oral or injectable medication. Medicaid, Medicare Advantage, and commercial plan patients aged 19-89 years with continuous enrollment 6 months before and 12 months after the index date were included in the study. Outcomes were adjusted using propensity score by inverse probability of treatment weighting. Treatment discontinuation, switching, health care resource utilization, and costs were measured during the post-index period. RESULTS: Oral versus injectable users with joint (n = 458 vs. 3,875), skin (n = 265 vs. 951), or joint and skin (n = 171 vs. 805) conditions were identified. For drug utilization outcomes, no differences in discontinuation rates were observed between oral and injectable groups for any of the cohorts. However, those in skin and joint and skin cohorts had higher rates of switching to other immunotherapies in patients initiated on orals compared with injectables. Health care resource utilization outcomes were mixed. While mean outpatient and physician office visits were significantly higher in oral compared with injectable groups across all 3 cohorts, no differences were observed for inpatient stays. Total costs (medical plus pharmacy) were lower for oral groups across all 3 cohorts. Pharmacy costs were lower for oral groups, but medical costs were higher for oral groups across all 3 cohorts. CONCLUSIONS: This is the first population-level study at a route-of-administration level, which compared switching, health care resource utilization, and costs across several conditions. Switching drugs was more likely in the oral group, which may indicate lower effectiveness or tolerability of oral immunotherapies relative to injectables. Health care resource utilization was higher in the oral group, but total costs were lower, which was likely driven by the lower costs of oral drugs. DISCLOSURES: This study was a Humana internal study, and all authors were at the time employees of Humana and used Humana resources. The authors have no conflicts of interest or financial interests to disclose that relate to the research described in this study. This study was presented as a podium and poster presentation at the AMCP Managed Care & Specialty Pharmacy Annual Meeting; April 23-26, 2018; Boston, MA.

A Real-World Observational Study of Time to Treatment Intensification Among Elderly Patients with Inadequately Controlled Type 2 Diabetes Mellitus.

BACKGROUND: Among elderly patients, the management of type 2 diabetes mellitus (T2DM) is complicated by population heterogeneity and elderly-specific complexities. Few studies have been done to understand treatment intensification among elderly patients failing multiple oral antidiabetic drugs (OADs). OBJECTIVE: To examine the association between time to treatment intensification of T2DM and elderly-specific patient complexities. METHODS: In this observational, retrospective cohort study, elderly (aged ≥ 65 years) Medicare beneficiaries (n = 16,653) with inadequately controlled T2DM (hemoglobin A1c ≥ 8.0% despite 2 OADs) were included. Based on the consensus statement for diabetes care in elderly patients published by the American Diabetes Association and the American Geriatric Society, elderly-specific patient complexities were defined as the presence or absence of 5 geriatric syndromes: cognitive impairment; depression; falls and fall risk; polypharmacy; and urinary incontinence. RESULTS: Overall, 48.7% of patients received intensified treatment during follow-up, with median time to intensification 18.5 months (95% CI = 17.7-19.3). Median time to treatment intensification was shorter for elderly patients with T2DM with polypharmacy (16.5 months) and falls and fall risk (12.7 months) versus those without polypharmacy (20.4 months) and no fall risk (18.6 months). Elderly patients with urinary incontinence had a longer median time to treatment intensification (18.6 months) versus those without urinary incontinence (14.6 months). The median time to treatment intensification did not significantly differ by the elderly-specific patient complexities that included cognitive impairment and depression. However, after adjusting for demographic, insurance, clinical characteristics, and health care utilization, we found that only polypharmacy was associated with time to treatment intensification (adjusted hazard ratio, 1.10; 95% CI = 1.04-1.15; P = 0.001). CONCLUSIONS: Less than half of elderly patients with inadequately controlled T2DM received treatment intensification. Elderly-specific patient complexities were not associated with time to treatment intensification, emphasizing a positive effect of the integrated health care delivery model. Emerging health care delivery models that target integrated care may be crucial in providing appropriate treatment for elderly T2DM patients with complex conditions.

Health Behaviors Among Breast Cancer Patients and Survivors.

BACKGROUND: With improved treatments, the survival rate for breast cancer patients is increasing. With the improvements in quantity of life, research in the field of cancer survivorship has turned its attention to psychosocial functioning and health behaviors. OBJECTIVES: The purpose of this study was to examine how those currently under treatment and those completing treatment engaged in health behaviors (ie, diet, vitamin use, exercise, and cancer screening) and if psychosocial predictors, guided by the Self-regulation Model, also play a role. METHODS: Using the Self-regulation Model, the current survey and medical record review examined health behaviors (diet, vitamin use, exercise, cancer screening) in individuals in active treatment for breast cancer and in those completing treatment (n = 141). RESULTS: Regression models revealed that those in active treatment had less healthy food consumption, vitamin use, and clinical examinations than did treatment completers. Greater perceived treatment efficacy was associated with diet and vitamin use but not exercise or cancer screening. Greater perceived risk of recurrence was associated with less exercise. Greater distress was associated with greater mammography use. Those from metro areas had greater healthy food consumption. RESULTS: Qualitative data indicated that chemotherapy interfered with health behaviors for those in active treatment; treatment completers wished to have a healthier lifestyle. CONCLUSION: Cancer treatment interferes with health behaviors, and these health behaviors might help individuals manage their cancer treatment more effectively. IMPLICATIONS FOR PRACTICE: Those currently undergoing treatment desire assistance with a healthier lifestyle, and relevant clinical interventions should stress treatment efficacy.

Excess risk of chronic physical conditions associated with depression and anxiety.

BACKGROUND: Depression and anxiety have been reported to be associated with chronic physical conditions. We examined the excess risk of chronic physical conditions associated with depression and/or anxiety within a multivariate framework controlling for demographic and modifiable lifestyle risk factors. METHODS: We used a retrospective cross-sectional study design. Study participants were adults aged 22-64 years from 2007 and 2009 Medical Expenditure Panel Survey. We defined presence of depression-anxiety based on self-reported depression and anxiety and classified adults into 4 groups: 1) depression only; 2) anxiety only; 3) comorbid depression and anxiety 4) no depression and no anxiety. We included presence/absence of arthritis, asthma, chronic obstructive pulmonary disorder, diabetes, heart disease, hypertension, and osteoporosis as dependent variables. Complementary log-log regressions were used to examine the excess risk associated with depression and/or anxiety for chronic physical conditions using a multivariate framework that controlled for demographic (gender, age, race/ethnicity) and modifiable lifestyle (obesity, lack of physical activity, smoking) risk factors. Bonferroni correction for multiple comparisons was applied and p ≤0.007 was considered statistically significant. RESULTS: Overall, 7% had only depression, 5.2% had only anxiety and 2.5% had comorbid depression and anxiety. Results from multivariable regressions indicated that compared to individuals with no depression and no anxiety, individuals with comorbid depression and anxiety, with depression only and with anxiety only, all had higher risk of all the chronic physical conditions. ARRs for comorbid depression and anxiety ranged from 2.47 (95% CI: 1.47, 4.15; P = 0.0007) for osteoporosis to 1.64 (95% CI: 1.33, 2.04; P < 0.0001) for diabetes. Presence of depression only was also found to be significantly associated with all chronic conditions except for osteoporosis. Individuals with anxiety only were found to have a higher risk for arthritis, COPD, heart disease and hypertension. CONCLUSION: Presence of depression and/or anxiety conferred an independent risk for having chronic physical conditions after adjusting for demographic and modifiable lifestyle risk factors.