Effects of tolvaptan discontinuation in patients with autosomal dominant polycystic kidney disease: a post hoc pooled analysis.

BACKGROUND: Tolvaptan slows kidney function decline in patients with autosomal dominant polycystic kidney disease (ADPKD) who are at risk of rapid progression. Given that treatment requires commitment to long-term use, we evaluated the effects of tolvaptan discontinuation on the trajectory of ADPKD progression. METHODS: This was a post hoc analysis of pooled data from two clinical trials of tolvaptan (TEMPO 2:4 [NCT00413777] and TEMPO 3:4 [NCT00428948]), an extension trial (TEMPO 4:4 [NCT01214421]), and an observational study (OVERTURE [NCT01430494]) that enrolled patients from the other trials. Individual subject data were linked longitudinally across trials to construct analysis cohorts of subjects with a tolvaptan treatment duration > 180 days followed by an off-treatment observation period of > 180 days. For inclusion in Cohort 1, subjects were required have ≥ 2 outcome assessments during the tolvaptan treatment period and ≥ 2 assessments during the follow-up period. For Cohort 2, subjects were required to have ≥ 1 assessment during the tolvaptan treatment period and ≥ 1 assessment during the follow-up period. Outcomes were rates of change in estimated glomerular filtration rate (eGFR) and total kidney volume (TKV). Piecewise-mixed models compared changes in eGFR or TKV in the on-treatment and post-treatment periods. RESULTS: In the Cohort 1 eGFR population (n = 20), the annual rate of eGFR change (in mL/min/1.73 m2) was -3.18 on treatment and -4.33 post-treatment, a difference that was not significant (P = 0.16), whereas in Cohort 2 (n = 82), the difference between on treatment (-1.89) and post-treatment (-4.94) was significant (P < 0.001). In the Cohort 1 TKV population (n = 11), TKV increased annually by 5.18% on treatment and 11.69% post-treatment (P = 0.06). In Cohort 2 (n = 88), the annual TKV growth rates were 5.15% on treatment and 8.16% post-treatment (P = 0.001). CONCLUSIONS: Although limited by small sample sizes, these analyses showed directionally consistent acceleration in measures of ADPKD progression following the discontinuation of tolvaptan.

EGFR mutation testing and treatment decisions in patients progressing on first- or second-generation epidermal growth factor receptor tyrosine kinase inhibitors.

BACKGROUND: The objective of this study was to investigate real-world EGFR mutation testing in patients with metastatic non-small cell lung cancer (NSCLC) upon progression on first-/second-generation epidermal growth factor receptor (EGFR)-tyrosine kinase inhibitors (TKI), and subsequent treatments received. METHODS: Flatiron Health electronic health records-derived database was used to identify adult patients with metastatic NSCLC treated with first-/second-generation EGFR-TKI from 11/2015-09/2017, with start of first EGFR-TKI defined as the index date. Patients were stratified by receipt of EGFR-TKI as first-line (1 L) or later-line (2 L+) treatment. Mutation testing and subsequent therapies following first-/second-generation EGFR-TKI were described. RESULTS: Overall, 782 patients (1 L = 435; 2 L+ =347) were included. Median age was 69.0 years, 63.6% were female, 56.3% were white, 87.1% were treated in community-based practices, and 30.1% of patients died during the study period; median follow-up was 309.0 days. Among the 294 (1 L = 160; 2L+ =134) patients who received subsequent therapies, treatments included chemotherapy only (1 L = 15.6%; 2L+ =21.6%), immunotherapy only (1 L = 13.8%; 2 L+ =41.0%), and targeted therapies (1 L = 70.0%; 2 L+ =36.6%). Specifically, 40 (25.0%) 1 L patients and 7 (5.2%) 2 L+ patients received osimertinib as subsequent therapy. Before the start of subsequent therapy, EGFR T790M resistance mutation testing was performed in 88 (29.9%) patients (1 L = 63 [39.4%]; 2 L+ =25 [18.7%]). Of these patients, 25 (28.4%) were T790M positive, among whom 24 (96.0%) received osimertinib. CONCLUSIONS: A third of patients received subsequent therapies on disease progression; only 30% of these were tested for EGFR-TKI resistance mutation, prior to receiving subsequent therapies. These results highlight the importance of choosing treatments in the 1 L setting that optimize benefits for patients with EGFR-mutated NSCLC.

Patient preferences for attributes of tyrosine kinase inhibitor treatments for EGFR mutation-positive non-small-cell lung cancer.

Aim: EGFR-tyrosine kinase inhibitors (TKIs) vary in efficacy, side effects (SEs) and dosing regimen. We explored EGFR-TKI treatment attribute preferences in EGFR mutation-positive metastatic non-small-cell lung cancer. Materials & methods: Patients completed a survey utilizing preference elicitation methods: direct elicitation of four EGFR-TKI profiles describing progression-free survival (PFS), severe SE risk, administration; discrete choice experiment involving 12 choice tasks. Results: 90 participated. The preferred profile (selected 89% of times) had the longest PFS (18 months) and the lowest severe SE risk (5%). Patients would need compensation with ≥three-times longer PFS for severe SEs. Patients would accept ≤7 months PFS reduction for oral treatments versus intravenous. Conclusion: Patients preferred longer PFS but were willing to accept reduced PFS for more favorable SEs and dosing convenience.

Treatment patterns and overall survival among patients with unresectable, stage III non-small-cell lung cancer.

Aim: To analyze treatment patterns and overall survival (OS) across time (2009-2014) among patients with unresected, stage III non-small-cell lung cancer (NSCLC). Patients & methods: Stage III NSCLC patients aged ≥65 years who initiated therapy were identified using SEER-Medicare data. Results: Among 4564 patients, 84% received chemotherapy (with or without radiotherapy), and 59% received chemoradiotherapy (CRT). Carboplatin + paclitaxel was the most frequent regimen. Median (interquartile range) OS among chemotherapy patients was 13.2 (6.0-28.9) months, and 14.8 (6.7-33.4) months among CRT patients. Among CRT patients, there was no difference in OS across years of CRT initiation. Conclusion: OS remained static across 2009-2014, indicating stagnancy in clinical outcomes for stage III NSCLC patients and a need for more effective therapeutic options.

Real-world treatment patterns among patients with unresected stage III non-small-cell lung cancer.

Aim: Little is known about recent treatment patterns among patients with unresected stage III NSCLC in the real world. This retrospective study used medical records from USA community oncology practices to address this knowledge gap. Materials & methods: Eligible patients were stage III NSCLC adults diagnosed between 1 January 2011 and 1 March 2016 without surgical resection. Treatment patterns were assessed across three progression intervals, from stage III diagnosis through third progression. Results: The most common regimen in interval 1 was platinum doublet chemotherapy + radiation therapy, in interval 2 was chemotherapy only, and in interval 3 was non-platinum chemotherapy monotherapy. Conclusion: Most patients were treated following national guidelines, but important unmet needs remain.

Objective response rate is a possible surrogate endpoint for survival in patients with advanced, recurrent ovarian cancer.

OBJECTIVE: Evaluate literature to assess response rate as a surrogate endpoint of survival in ovarian cancer (OC). METHODS: Systematic review consistent with PRISMA criteria, identified randomized, controlled trials reporting overall survival (OS), progression-free survival (PFS), and objective response rate (ORR) in recurrent OC. MEDLINE® and Embase® searches (year 2000-March 23, 2015) were augmented by bibliographic screening. Proposed surrogate measures (independent variables) were ORR and disease control rate. True clinical outcomes (dependent variables) were median OS and PFS. Analyses were performed on unweighted and weighted data using correlation analysis, linear regression, and surrogate threshold effect (STE). Smaller STE indicates greater predictive precision with magnitude of STE dependent on variance of prediction. RESULTS: Thirty-nine studies were included for review, representing 9223 platinum-sensitive and resistant patients. Objective response rate (r=0.82; P<0.001) was a better predictor than disease control rate (r=0.58; P<0.001) and strongly correlated with PFS (r=0.85; P<0.0001). Weighted-regression analysis demonstrated that for each 10% increase in ORR, PFS increased by 1.20months and OS by 2.83months. Regression analysis of treatment effects (odds ratio of response, hazard ratio of survival) suggests that a 10% increase in odds ratio of ORR would result in 2.5% reduction in the hazard ratio of OS. Based on weighted data, STE indicated that an ORR of ≥1% is needed to achieve nonzero OS benefit. CONCLUSION: This systematic review supports ORR as a possible surrogate clinical trial endpoint for OS in recurrent OC with at least second-line therapy.

Impact of primary platinum-free interval and BRCA1/2 mutation status on treatment and survival in patients with recurrent ovarian cancer.

OBJECTIVE: To understand the relationship between primary platinum-free interval (PFI), BRCA mutation status, and overall survival (OS) in patients with recurrent ovarian cancer receiving multiple lines of therapy in a multicenter, community-based, retrospective observational cohort study of adult patients with stage III-IV high-grade ovarian cancer. METHODS: Data were retrospectively obtained from the electronic health record (EHR) of a US community oncology network, including patient characteristics, subsequent treatments, primary PFI, and BRCA status. OS was analyzed by the Kaplan-Meier method, stratified by primary PFI and BRCA status. RESULTS: 750 patient charts were reviewed. BRCA testing status was known in 267 patients (16% BRCA mutation). Among patients with identified recurrent disease, 41% had a primary PFI <6months and 59% had a primary PFI ≥6months. Of second-line patients, 59% received third-line therapy, and 60% of third-line patients received fourth-line therapy within the period of observation. Median OS from the start of primary treatment for the entire population was 41.4months (95% CI, 39.0-48.3months). Median OS was significantly increased in patients with primary PFI ≥6months at second-line and third-line (P<0.0001 and P=0.002, respectively). Survival was observed to be increased among patients with BRCA mutations across multiple treatment lines, although this was not statistically significant. CONCLUSIONS: Patients with a primary PFI ≥6months demonstrated improved outcomes over multiple lines of therapy. BRCA status was known in 36% of patients, and those patients with a BRCA mutation demonstrated a trend toward delayed primary recurrence and improved clinical outcomes.

Epidemiology of adult idiopathic inflammatory myopathies in a U.S. managed care plan.

INTRODUCTION: Idiopathic inflammatory myopathies have a reported incidence of 0.1 to 1 per 100,000 person-years and prevalence of 0.55 to 6 per 100,000 in the United States. METHODS: We retrospectively examined medical claims for adults aged ≥18 years with myositis (International Classification of Diseases, Ninth Revision, Clinical Modification codes 710.3 [dermatomyositis], 710.4 [polymyositis], and 728.81 [interstitial myositis]) from 2003 to 2008 in a large US managed care database. RESULTS: The incidence and prevalence cohorts comprised 1,941 and 3,112 subjects, respectively. From 2003 to 2008, the adjusted annual incidence of myositis ranged from 5.8 to 7.9 per 100,000 person-years, and the annual prevalence of myositis ranged from 14.0 to 17.4 per 100,000. CONCLUSIONS: The incidence and prevalence of idiopathic inflammatory myopathies in the managed care plan studied was higher than previously reported in the United States. Because of the limitations inherent in claims analysis, additional research is needed to substantiate these results.

Medical costs and health-care resource use in patients with inflammatory myopathies in an insured population.

INTRODUCTION: In this study we determined the health-care costs and resource utilization associated with idiopathic inflammatory myopathies (IIMs) in a large managed care plan in the USA. METHODS: Myositis subjects ≥18 years of age with claims-based evidence of IIMs were identified from a health plan database. Subjects were matched with unaffected controls, and costs and resource use were determined during a 12-month period. RESULTS: A total of 1781 newly diagnosed IIM subjects were matched to 5343 controls, and 2697 subjects with existing disease were matched to 8091 controls. Mean overall annual medical costs were higher among newly diagnosed subjects ($16,319 vs. $4926, P < 0.001) and subjects with an existing IIM ($15,539 vs. $5210, P < 0.001) in comparison to controls. IIM subjects had significantly higher mean counts of ambulatory visits, specialist visits, and inpatient hospital stays compared with controls (all P < 0.001). CONCLUSION: Our analysis suggests that IIMs have increased medical costs and resource use.

Incidence and prevalence of idiopathic inflammatory myopathies among commercially insured, Medicare supplemental insured, and Medicaid enrolled populations: an administrative claims analysis.

BACKGROUND: Idiopathic inflammatory myopathies (IIMs) are a rare group of autoimmune syndromes characterized by chronic muscle inflammation and muscle weakness with no known cause. Little is known about their incidence and prevalence. This study reports the incidence and prevalence of IIMs among commercially insured and Medicare and Medicaid enrolled populations in the US. METHODS: We retrospectively examined medical claims with an IIM diagnosis (ICD-9-CM 710.3 [dermatomyositis (DM)], 710.4 [polymyositis (PM)], 728.81[interstitial myositis]) in the MarketScan® databases to identify age- and gender-adjusted annual IIM incidence and prevalence for 2004-2008. Sensitivity analysis was performed for evidence of a specialist visit (rheumatologist/ neurologist/dermatologist), systemic corticosteroid or immunosuppressant use, or muscle biopsy. RESULTS: We identified 2,990 incident patients between 2004 and 2008 (67% female, 17% Medicaid enrollees, 27% aged ≥65 years). Overall adjusted IIM incidence for 2004-2008 for commercial and Medicare supplemental groups combined were 4.27 cases (95% CI, 4.09-4.44) and for Medicaid, 5.23 (95% CI 4.74-5.72) per 100,000 person-years (py). Disease sub-type incidence rates per 100,000-py were 1.52 (95% CI 1.42-1.63) and 1.70 (1.42-1.97) for DM, 2.46 (2.33-2.59) and 3.53 (3.13-3.94) for PM, and 0.73 (0.66-0.81) and 0.78 (0.58-0.97) for interstitial myositis for the commercial/Medicare and Medicaid cohorts respectively. Annual incidence fluctuated over time with the base MarketScan populations. There were 7,155 prevalent patients, with annual prevalence ranging from 20.62 to 25.32 per 100,000 for commercial/Medicare (83% of prevalent cases) and from 15.35 to 32.74 for Medicaid. CONCLUSIONS: We found higher IIM incidence than historically reported. Employer turnover, miscoding and misdiagnosing, care seeking behavior, and fluctuations in database membership over time can influence the results. Further studies are needed to confirm the incidence and prevalence of IIM.

Mortality and morbidity among infants at high risk for severe respiratory syncytial virus infection receiving prophylaxis with palivizumab: a systematic literature review and meta-analysis.

OBJECTIVES: A systematic literature review and meta-analysis was performed to evaluate the impact of prophylaxis with palivizumab on mortality and morbidity associated with respiratory syncytial virus infection in infants at high risk (≤ 35 wks of gestational age, chronic lung disease, or congenital heart disease). DATA SOURCES: MEDLINE, EMBASE, and Current Contents were used. MEDLINE was searched from January 1, 1990 to May 16, 2007. The bibliographies of accepted studies and recent reviews and proceedings from the past 2 yrs were searched to identify additional relevant studies. STUDY SELECTION: Randomized controlled trials and prospective or retrospective cohort studies evaluating all-cause and respiratory syncytial virus-specific mortality, respiratory syncytial virus hospitalizations, and health care use in infants at high risk for respiratory syncytial virus infection receiving prophylaxis with palivizumab. DATA EXTRACTION: Data elements from each accepted study were extracted by one researcher and confirmed by a second researcher. Differences were resolved before data entry and analysis. DATA SYNTHESIS: A total of 2473 citations were screened and ten comparative studies of palivizumab prophylaxis evaluating >15,000 infants were included. Comparisons of mortality and hospitalization outcomes between infant groups using prophylaxis and not using prophylaxis were made using meta-analyses. CONCLUSIONS: Prophylaxis and nonprophylaxis infant groups appeared to be comparable at baseline. All-cause mortality during the respiratory syncytial virus season was 12 of 6380 (0.19%) for infants with prophylaxis vs. 33 of 8182 (0.53%) for infants without prophylaxis (Peto odds ratio, 0.30; 95% confidence interval, 0.17-0.55). Only five respiratory syncytial virus-specific deaths were reported, and the majority of the studies did not report respiratory syncytial virus-related deaths. The rate of respiratory syncytial virus hospitalization was significantly lower among preterm infants with prophylaxis compared with those without prophylaxis (4.1% vs. 10.4%; odds ratio, 0.35; 95% confidence interval, 0.25-0.47). Prophylaxis with palivizumab was associated with a reduction in all-cause mortality and respiratory syncytial virus hospitalization among preterm infants at high risk. Additional research on cause of death among infants at high risk is needed.

Prevalence of respiratory syncytial virus (RSV) risk factors and cost implications of immunoprophylaxis to infants 32 to 35 weeks gestation for health plans in the United States.

BACKGROUND: During the period of this study, the American Academy of Pediatrics (AAP) 2006 guidelines recommended respiratory syncytial virus (RSV) prophylaxis for infants 32 to 35 weeks gestation age (wGA) with two or more of five risk factors (RFs). New recommendations have recently been published in 2009. The cost implications of expanding this list of RFs to include other evidence-based RFs like passive smoke exposure (PSE), crowded living conditions (CLCs), and young chronological age (YCA) are unclear. METHODS: We estimated the prevalence of RSV RFs in a US sample of infants 32 to 35 wGA referred for prophylaxis from nine specialty pharmacy providers during the 2007-2008 season. We estimated the percent eligible for RSV prophylaxis under various potential RF coverage policies. Using a budget impact model, we calculated the per-member-per-month (PMPM) cost for each policy in 2007 USD for a hypothetical one million member plan. RESULTS: Infants 32 to 35 wGA represented 0.08% of the plan. Approximately 20.2% of these infants met at least two or more of five AAP RFs. Expanding this list to include one additional RF of PSE, CLC, or YCA increased the percent of infants potentially prophylaxed to 29.9%, 23.9%, and 47%, respectively. Adding all three RFs to the list (two or more of eight) increased the percent of infants potentially prophylaxed to 55.6%, and increased payer costs by 9 cents PMPM. CONCLUSION: Expanding the AAP RF criteria to include PSE, CLC, and YCA would identify more 32 to 35 wGA infants at high risk for severe RSV disease at an acceptable budget impact.

A systematic review of compliance with palivizumab administration for RSV immunoprophylaxis.

BACKGROUND: Respiratory syncytial virus (RSV) is a leading cause of lower respiratory tract infection (LRTI) in infants and young children, accounting for approximately 75,000-125,000 hospitalizations per year. It is estimated that in 2000, RSV infection accounted for 1.7 million office visits, 402,000 emergency room visits, and 236,000 hospital outpatient visits per year for children younger than 5 years of age. Palivizumab, a humanized monoclonal antibody directed against RSV, is the only immunoprophylaxis therapy approved by the FDA for prevention of serious lower respiratory tract disease caused by RSV in infants (up to 2 years of age) who meet 1 or more of the following criteria for high risk: (a) gestational age up to 35 weeks;(b) diagnosis of chronic lung disease (CLD, formerly bronchopulmonary dysplasia [BPD]); or (c) diagnosis of cyanotic or complex congenital heart disease. The RSV season typically occurs between November and March but may vary by region. During the period of our review, depending on local duration of the RSV season, infants usually required 5 monthly (every 28-30 days) intramuscular injections of palivizumab. Infants born in the middle of the season received their palivizumab doses from the time of birth to the end of the season and, therefore, may have required less than 5 doses.It is unclear if compliance with monthly doses is a problem and whether noncompliance increases the risk of RSV hospitalizations in routine clinical practice. OBJECTIVES: To (a) identify and describe compliance rates and the factors that influence parental compliance with immunoprophylaxis regimens, (b)review intervention programs and describe those that have been associated with increased compliance, and (c) summarize the association of compliance with RSV hospitalization rates. METHODS: An electronic literature search was conducted using journal databases, including Ovid, Current Contents, Embase, Medline In-Process & Other Non-Indexed Citations; Ovid Medline, PubMed, and Web of Science;and an abstract database, Medical Intelligence Solution, for citations through April 2008. Specific search terms used were palivizumab with patient compliance, patient adherence, or patient persistence. RESULTS: Twenty-five articles and abstracts met the inclusion criteria. Available studies were mostly retrospective or observational prospective.Compliance, defined in various ways across the studies, varied between 25% and 100%, and 12 studies identified some of the factors related to noncompliance. Compliance generally was lower among Medicaid patients,African American patients, and other minorities. Ten studies (3 manuscripts and 7 abstracts) investigated the association of administration of prophylaxis through monthly home visits by a health professional with parental compliance with therapy. Most of the home-based programs were associated with higher compliance rates compared with clinic or office programs.Rates as high as 94% and 64% were achieved when Medicaid infants and infants of minority descent, respectively, received their doses through a home health program. When these infants received their doses at a clinic or office, depending on the definition of compliance, rates were 61%-100% for Medicaid infants and 44% for infants of minority descent. Reminder telephone calls to parents or caregivers, comprehensive multidisciplinary programs that included extensive counseling of parents, calendars with sticker reminders, and education in the language native to parents also were associated with increased compliance, although statistical significance was reported in only 1 study. Several studies recommended educating parents on the benefits of RSV prophylaxis, alleviating transportation and language difficulties, recognizing cultural differences and biases, and clarifying misperception of RSV illness severity. Home health programs had lower rates of RSV hospitalizations than office-based programs in 3 analyses conducted in 2 studies. In 4 other abstracts, the rates of RSV hospitalization for home health programs and office-based administration did not significantly differ. In a large, 4-season, prospective outcome study, compliant infants had lower RSV hospitalization rates than those who were not compliant under one definition of compliance (doses within 35-day intervals). RSV hospitalization rates were not significantly different using another definition of compliance (receipt of anticipated doses, expected vs. observed rates).In a large survey of 10,390 infants identified from pharmacy dispensing records, RSV hospitalization rates were 1.4% in the compliant group versus 3.1% in the noncompliant group (OR = 2.2, 95% CI = 1.4-3.5, P < 0.001).Adjustment for confounding was not reported in these studies. CONCLUSION: Medicaid and minority infants were less likely to receive scheduled palivizumab doses. Home-based programs for the administration of palivizumab have been investigated more than other interventions and are associated with improved compliance compared with office-based administration. Compliance with dosing, in general, was associated with lower RSV hospitalization rates. However, these strategies should be further investigated using well-designed studies.

The rate of occurrence, healthcare resource use and costs of adverse events among metastatic non-small cell lung cancer patients treated with first- and second-generation epidermal growth factor receptor tyrosine kinase inhibitors.

OBJECTIVES: Clinical trials with first- and second-generation epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) reported severe adverse events (SAEs) in 6%-49% of patients with EGFR-mutated non-small cell lung cancer. This study describes incremental healthcare resource utilization (HRU) and costs associated with real-world management of AEs in this population, with a focus on SAEs. MATERIALS AND METHODS: Patients receiving erlotinib, gefitinib, or afatinib as first-line (1L) monotherapy were identified from IQVIA™ Real-World Data Adjudicated Claims-US database (04/01/2012-03/31/2017). Relevant AEs were selected from corresponding prescribing information; SAEs were identified from hospitalization claims. HRU and cost per-patient-per-month (PPPM) were assessed during 1L treatment and compared for patients with and without each AE using multivariate Poisson and linear regression, respectively, adjusting for baseline characteristics. RESULTS: Of 1646 patients, 86.9% were treated with erlotinib, 12.1% with afatinib, and 1.0% with gefitinib. In 1L, 12.2% of patients had ≥1 acute SAE (220.1/1000 patient-years). Patients with any SAE had higher PPPM costs than patients without SAEs (cost difference = $4700, p < 0.001). Incremental costs ranged from $2604 PPPM for diarrhea to $10,143 PPPM for microangiopathic hemolytic anemia (MAHA), and were statistically significant for all SAEs (all p < 0.001) except MAHA (p < 0.0528). Patients with any SAEs had higher rates of HRU relative to patients without SAEs (hospitalization rate ratio = 6.15; outpatient visits rate ratio = 1.21; all p < 0.001). CONCLUSION: More than one-tenth of patients experienced SAEs, resulting in sizeable economic burden with respect to HRU and costs. EGFR-TKIs with more favorable safety profiles may reduce the burden of managing this population.

Real-world outcomes in patients with unresected stage III non-small cell lung cancer.

This study examined real-world clinical outcomes such as progression-free survival (PFS), time to metastasis (TTM), overall survival (OS), and health-related quality of life (HRQOL) in patients with unresected stage III non-small cell lung cancer (NSCLC) treated in the community setting. A retrospective review of medical records extracted from 10 US community oncology practices was conducted. Eligible patients were adults diagnosed with stage III NSCLC from 1/1/2011 to 3/1/2016 without evidence of surgical resection within 6 months after stage III NSCLC diagnosis (index date). PFS, OS, and TTM were assessed from the index date, and were analyzed using Kaplan-Meier and Cox regression analyses. HRQOL was assessed for a subset of patients using a patient-reported measure, the 86-item Patient Care Monitor (PCM). Linear mixed models (LMM) were used to assess the impact of patient characteristics and change in PCM scores associated with progression. Among the sample of 478 patients, median PFS (95% confidence interval) was 10 months (9-11), median OS was 20 months (17-22), and median TTM was 30 months (23-45). Most patients (58.2%) experienced disease progression, which the LMM showed to be associated with significant worsening of physical symptoms and psychological states (p < 0.001). This study documented PFS and OS consistent with published literature. The majority of patients experienced disease progression, which was associated with worsening of HRQOL. These findings highlighted the need for better therapeutic options in patients with unresected stage III NSCLC with potential to improve patient outcomes and HRQOL.

Complications and Economic Burden Associated With Obtaining Tissue for Diagnosis and Molecular Analysis in Patients With Non-Small-Cell Lung Cancer in the United States.

PURPOSE: With an increase in biomarker-directed therapies, tissue biopsy to identify targetable genomic and immunologic alterations has become the mainstay of managing patients with non-small-cell lung cancer (NSCLC); however, little is known about the associated economic impact and complication rate. This study assesses the frequency, complications, and costs of diagnostic and postprogression biopsy. METHODS: This retrospective, observational study was conducted using administrative claims data from more than 30 million commercially insured individuals in the United States (2006 to 2014). Data were analyzed for the overall population and by time of biopsy (diagnostic or postprogression biopsy). RESULTS: Of 20,013 eligible patients, 13,411 (67%) received a diagnostic biopsy, whereas only 2,056 (10%) received a postprogression biopsy (mean cost, $9,977 and $16,806, respectively). Complication rates were similar at diagnosis and after progression, on the day of biopsy (10% v 7%, respectively) and within 30 days (63% v 61%, respectively). Mean costs were higher among patients with a complication compared with those without a complication on the day of biopsy (diagnostic biopsy, $12,030 v $6,508, respectively; postprogression biopsy, $22,593 v $7,812, respectively), within 7 days of biopsy (diagnostic biopsy, $13,657 v $7,765, respectively; postprogression biopsy, $23,969 v $8,932, respectively), and within 30 days of biopsy (diagnostic biopsy, $24,968 v $15,988, respectively; postprogression biopsy, $30,293 v $12,494, respectively; P < .001 for all comparisons). CONCLUSION: From 2006 to 2014, postprogression biopsies were not common practice in NSCLC. Complication rates were similar at diagnosis and after progression, with mean costs higher among patients with a complication than those without a complication. With increasing demands for effective novel targeted therapies and safe testing methods, these data may be valuable in determining the budget impact and comparing complication rates with newer, less invasive molecular testing methods, including plasma circulating tumor DNA testing.

Healthcare costs in patients with advanced non-small cell lung cancer and disease progression during targeted therapy: a real-world observational study.

AIMS: To assess healthcare costs during treatment with epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) and following disease progression in patients with advanced non-small cell lung cancer (NSCLC). METHODS: A retrospective analysis of medical records of US community oncology practices was conducted. Eligible patients had advanced NSCLC (stage IIIB/IV) diagnosed between January 1, 2008 and January 1, 2015, initiated treatment with erlotinib or afatinib (first-line or second-line), and had disease progression. Monthly Medicare-paid costs were evaluated during the TKI therapy period and following progression. RESULTS: The study included 364 patients. The total mean monthly cost during TKI therapy was $20,106 (95% confidence interval [CI] = $16,836-$23,376), of which 47.0% and 42.4% represented hospitalization costs and anti-cancer therapy costs, respectively. Following progression on TKI therapy (data available for 316 patients), total mean monthly cost was $19,274 (95% CI = $15,329-$23,218), and was higher in the 76.3% of patients who received anti-cancer therapy following progression than in the 23.7% of those who did not ($20,490 vs $15,364; p < .001). Among patients who received it, anti-cancer therapy ($11,198; 95% CI = $7,102-$15,295) represented 54.7% of total mean monthly cost. Among patients who did not receive anti-cancer therapy, hospitalization ($13,829; 95% CI = $4,922-$22,736) represented 90.0% of total mean monthly cost. Impaired performance status and brain metastases were significant predictors of increased cost during TKI therapy. LIMITATIONS: The study design may limit the generalizability of findings. CONCLUSIONS: Healthcare costs during TKI treatment and following progression appeared to be similar and were largely attributed to hospitalization and anti-cancer therapy. Notably, almost one-quarter of patients did not receive anti-cancer therapy following progression, potentially indicating an unmet need; hospitalization was the largest cost contributor for these patients. Additional effective targeted therapies are needed that could prolong progression-free survival, leading to fewer hospitalizations for EGFR mutation-positive patients.

Patient Characteristics and Costs in Recurrent or Refractory Head and Neck Cancer: Retrospective Analysis of a Community Oncology Database.

PURPOSE: The goal of this study was to describe patient characteristics, health resource utilization (HRU), and costs associated with treating recurrent or refractory head and neck cancer (HNC) among patients with disease progression in the community oncology setting. METHODS: This retrospective observational study was conducted by using data from the Vector Oncology Data Warehouse. Patients had been diagnosed with locally advanced or metastatic (stage III-IVc) HNC between January 1, 2007, and October 1, 2015. Patients also had evidence of at least 1 systemic anticancer therapy regimen following the diagnosis of advanced HNC, with at least 1 disease progression. Costs, treatment patterns, and HRU were evaluated beginning with diagnosis of advanced HNC through 3 lines of therapy. Costs of surgery or radiation were not available for inclusion in the analysis. Total cost for the study period and cost per month were analyzed by using a generalized linear regression model. FINDINGS: The study included 462 patients (median age, 61 years; range, 26-99 years); of these, 81% were male, 77% were white, and 21% were black. At initial diagnosis, the most frequent tumor locations were the hypopharynx/larynx (31%) and the oropharynx (31%). Human papilloma virus testing was most frequent among the oropharynx group (22% tested, 52% positive). Overall, 42% were current tobacco users and 22% were current or past alcohol abusers/excessive users. Platinum-based combination therapies were the most frequently administered chemotherapy in both first (42%) and second (40%) lines of treatment. Through the overall study period (mean, 20.5 months), 74% of patients were hospitalized, 19% had an emergency department visit, and 100% had an office visit. The overall mean (SD) duration of hospital stay was 12.6 days, and the median number of office visits per patient was 35. The mean monthly health care cost for the overall study period was $14,391 (95% CI, 12,739-16,044). Hospitalization costs represented ~57% of the total expenditures. Statistically significant predictors of higher overall cost included primary tumor location in the oral cavity, history of alcohol abuse/excess use, use of cetuximab, and higher comorbidity index. Older age and being stage IV versus other stages of disease at diagnosis were associated with lower overall cost. IMPLICATIONS: These data suggest that costs of care in patients with recurrent or refractory HNC are related to patient characteristics and treatment patterns. Identification of factors contributing to the costs of care in HNC may provide a useful foundation for developing strategies to control rising costs.

Effectiveness Outcomes in Patients With Recurrent or Refractory Head and Neck Cancers: Retrospective Analysis of Data From a Community Oncology Database.

PURPOSE: The purpose of this study was to provide an understanding of the effectiveness of existing therapies in patients with advanced head and neck cancer (HNC), particularly in clinical practice. METHODS: Data from the electronic medical records of adult patients diagnosed with locally advanced or metastatic (Stage III-IVc) HNC between January 1, 2007, and October 1, 2015, were retrospectively collected from a network of community oncology practices in the United States. Eligible patients experienced disease progression despite having received prior systemic therapy. Kaplan-Meier and Cox regression analyses of progression-free survival (PFS) and overall survival (OS) were conducted. Patient-reported outcomes were also collected. FINDINGS: The study included 462 patients (median age 61.0 years; 80.7% male; 77.1% white). Most patients had a history of tobacco use (41.8% current, 41.8% past), and human papillomavirus testing was infrequent overall (11.0%). The median overall duration of follow-up was 16.4 months (range, 2.3-85.2 months). Median PFS values were 8.45 months with first-line treatment and 5.33 months with second-line treatment. PFS with first-line treatment was significantly associated with primary tumor location, performance status, and tobacco use. Performance status was a predictor of PFS in second-line treatment. Median OS values were 21.04 and 9.53 months from the start of the first and second lines of therapy, respectively. Abuse/excessive use of alcohol, older age, and impaired performance status were associated with a significantly increased risk for death in outcomes analyses. Outcomes were worse among patients initially diagnosed with Stage IVc disease versus those who progressed to Stage IVc. Past tobacco use and alcohol abuse were associated with worse patient-reported symptoms such as dry mouth and sore throat (smoking) and trouble swallowing (alcohol). IMPLICATIONS: This study of data from clinical practice shows that there remains a large unmet need for effective therapeutic options in advanced HNC. Patients' characteristics such as alcohol use and performance status were statistically significant predictors of PFS and OS in Stage III-IVc HNC.