Raluca Ionescu-Ittu

Impact of low-grade adverse events on health-related quality of life in adult patients receiving imatinib or nilotinib for newly diagnosed Philadelphia chromosome positive chronic myelogenous leukemia in chronic phase

Abstract Objective: Chronic myeloid leukemia (CML) treatment relies on tyrosine kinase inhibitors (TKIs), but their use can be associated with low-grade adverse events (AEs). This analysis aimed to identify the low-grade AEs which significantly impact the Health Related Quality of Life (HRQoL) of CML patients in chronic phase (CP) and to compare the incidence of such AEs among nilotinib- and imatinib-treated patients. Research design and methods: Data from the 48 month ENESTnd trial were used (N = 593 patients). HRQoL was assessed using generic (SF-36) and leukemia-specific (FACT-Leu) HRQoL surveys. AEs were categorized into 26 system organ classes. Results: In the adjusted regression model, five low-grade AE categories – gastrointestinal disorders, blood and lymphatic system disorders, general disorders and administration site conditions, musculoskeletal disorders, and psychiatric disorders – significantly impaired at least one HRQoL score. The incidence rate of these five AE categories was either significantly lower for nilotinib than imatinib or not different between the two drugs. The AE categories with lower incidence for both nilotinib 300 mg BID and 400 mg BID versus imatinib 400 mg daily were gastrointestinal, blood and lymphatic system, and musculoskeletal; nilotinib 300 mg BID had lower incidence than imatinib for general disorders. Limitations: Low-grade AEs were grouped and analyzed by system organ class category, so the effect of some rare individual AEs on HRQoL may have been missed. Conclusions: The impact of low-grade AEs on HRQoL should be taken into account, along with other factors, when selecting the optimal treatment for patients newly diagnosed with CML-CP.

Comparing nilotinib with dasatinib as second-line therapies in patients with chronic myelogenous leukemia resistant or intolerant to imatinib – a retrospective chart review analysis

Abstract Introduction: This study compared progression, progression-free survival (PFS), overall survival (OS), and treatment changes among chronic myelogenous leukemia patients in chronic phase (CML-CP) receiving nilotinib or dasatinib as second-line therapy. Patients and methods: Information on CML-CP patients switched from imatinib to nilotinib or dasatinib as second-line therapy was collected retrospectively from 122 US hematologists and oncologists through an online medical chart review. Progression, PFS, and OS were compared using multivariate Cox proportional hazard models, and treatment changes using chi-square tests. Results: Of 597 imatinib resistant or intolerant patients, 301 initiated nilotinib and 296 dasatinib as second-line therapy. Nilotinib was associated with a lower risk of progression (hazard ratio [HR] = 0.27; p = 0.021) and longer PFS (HR = 0.48; p = 0.030) than dasatinib, with a median follow-up time of 11 months for nilotinib and 10 months for dasatinib. Nilotinib patients had a lower estimated hazard of mortality than dasatinib patients, though not statistically significant (HR = 0.46; p = 0.067). When treatment changes were classified by the physicians’ justifications, fewer nilotinib patients had treatment changes due to ineffectiveness (2.0% vs. 5.1%, p = 0.041) or drug holidays due to intolerance (0.0% vs. 1.7%, p = 0.024) than dasatinib patients. Conclusions: Among CML-CP patients in this retrospective chart review who switched from imatinib to either nilotinib or dasatinib, nilotinib was associated with a significantly lower risk of progression and longer PFS than dasatinib. Nilotinib patients were also less likely than dasatinib patients to subsequently have treatment changes due to ineffectiveness or drug holidays due to intolerance. These findings could be subject to unobserved confounders.

Comparison of survival and hospitalization rates between Medicare patients with advanced NSCLC treated with bevacizumab–carboplatin–paclitaxel and carboplatin–paclitaxel: A retrospective cohort study

OBJECTIVE The use of bevacizumab in advanced non-squamous non-small cell lung cancer (NSCLC) is controversial among elderly patients. This study aimed to compare overall survival for Medicare patients diagnosed with NSCLC and treated with either first-line bevacizumab-carboplatin-paclitaxel (BCP) or carboplatin-paclitaxel (CP). METHODS Patients ≥ 65 years old, first diagnosed with non-squamous NSCLC stage IIIB/IV between 2006 and 2009, and treated with either first-line BCP or CP, were selected from the SEER-Medicare database that links cancer registry and US Medicare claims data. Kaplan-Meier estimates were used to evaluate survival. Multivariable Cox proportional hazards models were used to compare the effect of BCP versus CP on the hazard of death. Age-stratified analyses were conducted for patients aged 65-74 and ≥ 75 years. RESULTS Of 1706 patients in the study sample, 592 (34.7%) received BCP and 1114 (65.3%) received CP; 692 (40.6%) were ≥ 75 years. Adjusted median survival time in the BCP versus CP cohorts was 10.5 versus 8.5 months (p = 0.008). The difference in median survival favoring the BCP cohort was statistically significant for both patients aged ≥ 75 years (2.8 months, p = 0.019), and patients aged 65-74 years (1.5 months, p = 0.018). The adjusted hazard of death did not differ between the cohorts (HR: 0.96, 95% CI: 0.86-1.06); however, during the first year of follow-up, when most deaths (>60%) occurred, the hazard of death was 18% lower for the BCP cohort (HR: 0.82, 95% CI: 0.71-0.94). BCP patients also had 18% fewer hospital admissions than CP patients (adjusted incidence rate ratio (IRR): 0.82, 95% CI: 0.72-0.94) and 23% fewer inpatient days (IRR: 0.77, 95% CI: 0.65-0.91). CONCLUSIONS In this retrospective analysis of Medicare patients in the SEER database, first-line therapy with BCP was associated with longer survival and fewer hospitalizations than CP.

Distribution and drivers of costs in type 2 diabetes mellitus treated with oral hypoglycemic agents: a retrospective claims data analysis.

Abstract Objective: To describe the distribution of costs and to identify the drivers of high costs among adult patients with type 2 diabetes mellitus (T2DM) receiving oral hypoglycemic agents. Methods: T2DM patients using oral hypoglycemic agents and having HbA1c test data were identified from the Truven MarketScan databases of Commercial and Medicare Supplemental insurance claims (2004–2010). All-cause and diabetes-related annual direct healthcare costs were measured and reported by cost components. The 25% most costly patients in the study sample were defined as high-cost patients. Drivers of high costs were identified in multivariate logistic regressions. Results: Total 1-year all-cause costs for the 4104 study patients were

Overall survival in patients with glioblastoma before and after bevacizumab approval

55,599,311 (mean cost per patient = 

Access to Cancer Specialist Care and Treatment in Patients With Advanced Stage Lung Cancer

13,548). Diabetes-related costs accounted for 33.8% of all-cause costs (mean cost per patient = 

Severe adverse events impact overall survival and costs in elderly patients with advanced non-small cell lung cancer on second-line therapy

4583). Medical service costs accounted for the majority of all-cause and diabetes-related total costs (63.7% and 59.5%, respectively), with a minority of patients incurring >80% of these costs (23.5% and 14.7%, respectively). Within the medical claims, inpatient admission for diabetes-complications was the strongest cost driver for both all-cause (OR = 13.5, 95% CI = 8.1–23.6) and diabetes-related costs (OR = 9.7, 95% CI = 6.3–15.1), with macrovascular complications accounting for most inpatient admissions. Other cost drivers included heavier hypoglycemic agent use, diabetes complications, and chronic diseases. Limitations: The study reports a conservative estimate for the relative share of diabetes-related costs relative to total cost. The findings of this study apply mainly to T2DM patients under 65 years of age. Conclusions: Among the T2DM patients receiving oral hypoglycemic agents, 23.5% of patients incurred 80% of the all-cause healthcare costs, with these costs being driven by inpatient admissions, complications of diabetes, and chronic diseases. Interventions targeting inpatient admissions and/or complications of diabetes may contribute to the decrease of the diabetes economic burden.

Stage III melanoma incidence and impact of transitioning to the 8th AJCC staging system: a US population-based study

Abstract Objective: Glioblastoma (GBM) is an aggressive disease with limited therapeutic options. While bevacizumab was approved in 2009 for the treatment of patients with progressive GBM, its impact on overall survival (OS) remains unclear. Using US population-based cancer registry data (SEER), this study compared OS of patients diagnosed with GBM before and after bevacizumab approval. Methods: Adult patients from SEER with a GBM diagnosis were divided into two cohorts: patients diagnosed in 2006–2008 (pre-bevacizumab cohort, n = 6,120) and patients diagnosed in 2010–2012 (post-bevacizumab cohort, n = 6,753). Patients were included irrespective of the treatments received. OS post-diagnosis was compared between the study cohorts utilizing Kaplan-Meier analyses and multivariate Cox proportional hazards regression. Results: Among 12,873 patients with GBM, the median age was 62 years, 41% were women, 31% underwent gross total resection, and 75% received radiation therapy. Survival was stable within the 2006–2008 period (median survival = 9 months for each year), but increased after year 2009 (median survival = 10 and 11 months for years 2010/2011 and 2012, respectively). The adjusted hazard of death was significantly lower in the post-bevacizumab approval cohort (hazard ratio = 0.91, p < .01). Conclusions: The results of this large population-based study suggested an improvement in OS among patients with a GBM diagnosis in 2010–2012 compared to 2006–2008. While the cause of this improvement cannot be proven in a retrospective analysis, the timing of the survival increase coincides with the approval of bevacizumab for the treatment of patients with progressive GBM, indicating a possible benefit of bevacizumab in this population.

Healthcare resource utilization in patients with metastatic melanoma receiving first-line therapy with dabrafenib + trametinib versus nivolumab or pembrolizumab monotherapy

Background Access to specialty care is critical for patients with advanced stage lung cancer. This study assessed access to cancer specialists and cancer treatment in a broad population of patients with advanced stage lung cancer. Materials and Methods Two study samples were extracted from 2 claims databases and analyzed independently: patients aged ≥ 18 years with de novo diagnosis of metastatic lung cancer in the MarketScan database between 2008 and 2014 (commercially insured adult patients; n = 22,268); and patients aged ≥ 65 years in the Surveillance, Epidemiology, and End Results–Medicare database with a diagnosis of advanced non–small‐cell lung cancer between 2007 and 2011 (Medicare‐insured elderly patients; n = 9651). The study period spanned from 6 weeks before the first lung biopsy tied to the initial lung cancer diagnosis until the end of continuous health insurance enrollment, or data availability, or death. Results Among the commercially insured adults (MarketScan), most patients were seen by a cancer specialist within a month of first lung biopsy (80%), 12% were never seen by a cancer specialist, and 6% did not receive cancer‐directed therapy. Among the Medicare‐insured elderly patients (SEER–Medicare), the proportions were 79%, 4%, and 10%, respectively. Patients seen by a cancer specialist were more likely to receive cancer‐directed therapy (95% vs. 92%, P < .001 and 92% vs. 38%, P < .001, respectively). Conclusion Between 4% and 12% of patients with advanced stage lung cancer do not have appropriate access to cancer specialist, which appears to negatively affect access to optimal and timely treatment. Micro‐Abstract MarketScan and Surveillance, Epidemiology, and End Results–Medicare databases were analyzed separately to evaluate the access to cancer specialists and treatment of patients with advanced stage lung cancer. Between 4% and 12% of the patients were never seen by a cancer specialist, and between 6% and 10% did not receive cancer‐directed therapy. Patients seen by a cancer specialist were more likely to receive cancer‐directed therapy.

Abstract 1209: Patterns of treatment with immune check point inhibitors and targeted therapy in patients with metastatic melanoma presumed BRAF V600 positive

OBJECTIVES Elderly patients with advanced non-small lung cancer (aNSCLC) represent a high-risk patient population due to disease burden, comorbidities, and performance status, particularly after progressing on first-line therapy. Among elderly patients who receive second-line therapy, treatment related toxicities can have substantial impact on both clinical and economic outcomes. This study assessed the impact of severe adverse events (AEs) during second-line therapy on overall survival (OS) and all-cause heathcare costs in elderly with aNSCLC. MATERIALS AND METHODS Patients with aNSCLC aged ≥65 years who initiated second-line chemotherapy/targeted therapy were identified in the SEER-Medicare database (2007-2011). Fifty-seven AEs were identified by literature review and consultation with two oncologists. Severe AEs were defined as AEs that required a hospitalization and were operationalized based on AE diagnosis(es) recorded during hospitalizations. OS post-second-line initiation and healthcare costs during second-line were compared between patients with and without severe AEs. RESULTS Among 3967 patients initiating second-line therapy, 1624 (41%) had ≥1 severe AE, where hypertension (26%), anemia (24%), and pneumonia (23%) were most commonly reported. Patients with and without severe AEs had similar demographic and cancer characteristics at diagnosis and similar second-line treatment regimens, but patients with severe AEs had more comorbidities at second-line initiation. Median OS was lower in patients with versus without severe AEs (6 vs. 11 months). After multivariate adjustment, hazard of death was more than twice higher in patients with versus without severe AEs (adjusted hazard ratio [HR] 2.31, 95% CI 2.16-2.47). Healthcare costs were more than twice higher in patients with versus without severe AEs (