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.

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.

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.

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.

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.

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.

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.

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.

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.

Validation of a Case-Finding Algorithm for Identifying Patients with Non-small Cell Lung Cancer (NSCLC) in Administrative Claims Databases.

Objective: To assess the validity of a treatments- and tests-based Case-Finding Algorithm for identifying patients with non-small cell lung cancer (NSCLC) from claims databases. Data sources: Primary data from the HealthCore Integrated Research Environment (HIRE)-Oncology database and the HealthCore Integrated Research Database (HIRD) were collected between June 1, 2014, and October 31, 2015. Study design: A comparative statistical evaluation using receiver operating characteristic (ROC) curve analysis and other validity measures was used to validate the NSCLC Case-Finding Algorithm vs. a control algorithm. Data collection: Patients with lung cancer were identified based on diagnosis and pathology classifications as NSCLC or small-cell lung cancer. Records from identified patients were linked to claims data from Anthem health plans. Three-month pre-index and post-index data were included. Principal findings: The NSCLC Case-Finding Algorithm had an area under the curve (AUC) of 0.88 compared with 0.53 in the control (p < 0.0001). Promising diagnostic accuracy was observed for the NSCLC Case-Finding Algorithm based on sensitivity (94.8%), specificity (81.1%), positive predictive value (PPV) (95.3%), negative predictive value (NPV) (79.6%), accuracy (92.1%), and diagnostic odds ratio (DOR) (78.8). Conclusions: The NSCLC Case-Finding Algorithm demonstrated strong validity for distinguishing patients with NSCLC from those with SCLC in claims data records and can be used for research into NSCLC populations.

Brain metastases in non-small cell lung cancer patients on epidermal growth factor receptor tyrosine kinase inhibitors: symptom and economic burden.

OBJECTIVE: This study describes the symptom and economic burden associated with brain metastases (BM) in patients with non-small cell lung cancer (NSCLC) receiving epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (EGFR-TKIs). METHODS: This retrospective study included adults with ≥2 medical claims, within 90 days, for lung cancer and ≥1 administration of EGFR-TKIs. Based on ICD-9 codes, patients were stratified into cohorts by type of metastases (BM, other metastases [OM], or no metastases [NM]), and by when the metastasis diagnosis occurred (synchronous or asynchronous). RESULTS: The population (synchronous BM [SBM] = 24, synchronous OM [SOM] = 23, asynchronous BM [ASBM] = 15, asynchronous OM [ASOM] = 49, NM = 85) was mostly female (57%), average age 69 years (SD = 11). SBM patients experienced more fatigue and nausea/vomiting compared with SOM and NM patients and more headaches and loss of appetite than NM patients. ASBM was associated with more fatigue, nausea/vomiting, headaches, pain/numbness, altered mental status, and seizures than NM, and more headaches and pain/numbness than ASOM. SBM patients experienced a greater increase in per-member-per-month all-cause total healthcare costs after diagnosis ($20,301) vs SOM ($9,131, p = .001) and NM ($2,493, p = .001). ASBM's cost increase between baseline and follow-up ($7,867) did not differ from ASOM's ($4,947, p = .195); both were larger than NM ($2,493, p = .001 and p = .009, respectively). LIMITATIONS: EGFR mutation status was inferred based on EGFR-TKI treatment, not by molecular testing. Patients were from US commercial insurance plans; results may not be generalizable to other populations. CONCLUSIONS: Among patients with EGFR-TKI-treated NSCLC, patients with BM experienced more symptoms and, when diagnosed synchronously, had significant increases in total medical costs vs patients with OM and NM. Therapeutic options with central nervous system activity may offer advantages in symptomatology and costs in EGFR-mutated patients with BM.

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.

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.

Increased Burden of Healthcare Utilization and Cost Associated with Opioid-Related Constipation Among Patients with Noncancer Pain.

BACKGROUND: Opioids are widely accepted as treatment for moderate to severe pain, and opioid-induced constipation is one of the most common side effects of opioids. This side effect negatively affects pain management and patients' quality of life, which could result in increased healthcare utilization and costs. OBJECTIVE: To assess healthcare utilization and costs (all-cause, constipation-related, and pain-related) for individuals with and without opioid-induced constipation during the 12 months after initiation of opioid therapy for noncancer pain. METHODS: This retrospective cohort study was conducted using administrative claims data from HealthCore Integrated Research Environment between January 1, 2006, and June 30, 2014. The analysis was limited to patients aged ≥18 years who filled a prescription for continuous opioid treatment (≥28 days) for noncancer pain. Propensity scores were used to match opioid users with constipation (cohort 1) and opioid users without constipation (cohort 2), using a 1:1 ratio. Generalized linear models were used to estimate all-cause, constipation-related, and pain-related healthcare utilization and costs during the 12 months after the initiation of opioid therapy. RESULTS: After matching and balancing for all prespecified variables, 17,384 patients were retained in each cohort (mean age, 56 years; 63% female). Opioid users with constipation were twice as likely as those without constipation to have ≥1 inpatient hospitalizations (odds ratio, 2.28; 95% confidence interval [CI], 2.17-2.39) during the 12 months. The total mean adjusted overall costs per patient during the study period were $12,413 higher for patients with constipation versus those without it (95% CI, $11,726-$13,116). The total mean adjusted overall pain-related costs per patient were $6778 (95% CI, $6293-$7279) higher for the patients with constipation than those without. Among patients using opioids for noncancer pain, the annual mean constipation-related costs per patient totaled $4646 (total average plan-paid costs, $4424; total patient-paid costs, $222). CONCLUSIONS: Patients using opioids with newly diagnosed constipation had significantly greater healthcare utilization and costs than patients without constipation; these costs accounted for approximately 16% of the total healthcare costs per patient during the 12-month study period. Recognition and effective treatment of opioid-induced constipation may decrease healthcare utilization for patients with chronic noncancer pain and may reduce the economic burden of pain therapy.

BRCA testing, treatment patterns and survival in platinum-sensitive recurrent ovarian cancer - an observational cohort study.

BACKGROUND: Breast cancer associated (BRCA) genes are critical for DNA repair. Mutations in BRCA1 and BRCA2 (BRCAm) result in loss of these repair mechanisms and potential carcinogenesis. Germline BRCAm are common in ovarian carcinomas, particularly in platinum-sensitive disease. The increased prevalence of BRCAm in platinum-sensitive disease is likely due to enhanced responsiveness to platinum chemotherapy from homologous recombination repair deficiency. The purpose of this study was to explore BRCA testing, treatment patterns and survival in platinum-sensitive recurrent (PSR) ovarian cancer. METHODS: This was an observational cohort analysis of PSR ovarian cancer treated at the Huntsman Cancer Institute from 1995 to 2012. Germline BRCA status was ascertained through chart review and categorized as BRCAm (BRCA1/2 positive), BRCAwt (BRCA wild type or variant of uncertain significance), and untested. Treatment patterns and survival were assessed from recurrence until death or last follow-up. The Kaplan-Meier method was used to evaluate survival from recurrence by BRCA status. Logistic regression and COX proportional hazard model was used to estimate predictors of BRCA testing and survival, respectively. RESULTS: Of the 168 PSR patients, 15 (9 %) were BRCAm, 25 (15 %) were BRCAwt, and 128 (76 %) were untested. Median age at PSR was 56 years for BRCAm and BRCAwt (p = 0.90) and 63 years for those untested (p = 0.033 vs BRCAm). Overall survival was similar between BRCAm and BRCAwt (median 50.4 vs 67.5 months, p = 0.86) and was 24.9 months in untested patients. Significant predictors for the likelihood of BRCA testing were age (OR = 0.93, 95 % CI 0.89, 0.97, p = 0.002), family history of breast or ovarian cancer (OR = 8.33, 95 % CI: 3.08, 22.59, p < 0.001), and cancer diagnosis year (OR = 10.02, 95 % CI: 3.22, 31.21, p < 0.001). BRCA-tested patients had a lower risk of death versus untested (HR 0.35, 95 % CI 0.17, 0.68, p = 0.001). CONCLUSIONS: BRCAwt patients had similar outcomes to BRCAm patients, potentially owing to similar age at diagnosis, representing a BRCA testing channeling bias. Younger patients, those with a family history of breast or ovarian cancer, and those diagnosed more recently were more likely to be BRCA tested. BRCA tested patients had a lower risk of death.

Impaired health status and the effect of pain and fatigue on functioning in clinical trial patients with systemic lupus erythematosus.

OBJECTIVE: Our study evaluated the impaired health status of clinical trial patients with systemic lupus erythematosus (SLE) and explored the relationship between changes in fatigue and pain and their effect on overall health status. METHODS: Pooled treatment and placebo data from a phase Ib clinical trial of adults with moderate/severe SLE were analyzed. Measures included patient-reported Medical Outcome Study Short Form-36 Survey, Version 2 (SF-36v2), Fatigue Severity Scale, and numeric rating scales (NRS) for pain and global health assessment and clinician-reported global assessment of disease activity (MDGA). Disease burden was compared to the US general population. Health status of responders and nonresponders on pain or fatigue were compared. RESULTS: The sample included 161 patients with SLE, predominantly female (96%) and white (72%), with average age of 43 ± 11 years. Mean SF-36v2 component summary scores reflected overall problems with physical [physical component summary (PCS); 35.2 ± 9.7] and mental health (mental component summary; 40.9 ± 12.9). Patients with SLE had worse health status on all SF-36v2 subscales than the US general population and comparable age and sex norms (effect size -0.51 to -2.15). Pain and fatigue responders had greater improvements on SF-36v2 scores (bodily pain, physical functioning, social functioning, PCS), patient global health assessment NRS, and MDGA than nonresponders. There was moderate agreement in responder status, based on global assessments by patients and clinicians (68.1%), with some discrepancy between patients who were MDGA responders but patient assessment nonresponders (27.7%). CONCLUSION: Improvements in patient-reported pain or fatigue correlated with improvements in overall health. Patient assessments offer a unique perspective on treatment outcomes. Patient-reported outcomes add value in understanding clinical trial treatment benefits.

Medical costs and healthcare resource use in patients with lupus nephritis and neuropsychiatric lupus in an insured population.

OBJECTIVE: Systemic lupus erythematosus (SLE) is a chronic autoimmune disease that can affect multiple organ systems, including the kidneys (lupus nephritis) and the central nervous system (neuropsychiatric lupus, or NPSLE). The healthcare costs and resource utilization associated with treating lupus nephritis and NPSLE in a large US managed care plan were studied. METHODS: SLE subjects ≥18 years of age and with claims-based evidence of nephritis or neuropsychiatric conditions were identified from a health plan database. An index date was set as a randomly drawn date from all qualifying claims during 2003-2008 for study subjects. Subjects were matched on the basis of demographic and clinical characteristics to unaffected controls. Costs and resource use were determined during a fixed 12-month post-index period. RESULTS: Nine hundred and seven lupus nephritis subjects were matched to controls, and 1062 subjects with NPSLE were matched to controls. Mean overall post-index healthcare costs were significantly higher among subjects with lupus nephritis in comparison to matched controls ($33,472 vs $5347, p < 0.001). Similarly, mean overall post-index healthcare costs were significantly higher among subjects with NPSLE compared to controls ($30,341 vs $4646, p < 0.001). Subjects with lupus nephritis or NPSLE had higher mean post-index numbers of ambulatory visits, specialist visits, emergency department visits and inpatient hospital stays, compared to controls (all p < 0.001). LIMITATIONS: Additional research, such as medical chart review, could provide validation for the claims-based identification of lupus nephritis and NPSLE subjects. Also, indirect costs were not evaluated in this study. CONCLUSION: Subjects with lupus nephritis or NPSLE have high costs and resource use, compared to unaffected controls.