Gebra Cuyun Carter

Comprehensive review of factors implicated in the heterogeneity of response in depression

Heterogeneity in overall response and outcomes to pharmacological treatment has been reported in several depression studies but with few sources that integrate these results. The goal of this study was to review the literature and attempt to identify nongenetic factors potentially predictive of overall response to depression treatments.

Heterogeneity of Response to Biologic Treatment: Perspective for Psoriasis

Psoriasis treatment responses are affected by patient characteristics. However, the literature does not contain reviews of factors that affect the response to biologic therapies. We therefore performed a comprehensive literature search to identify papers describing demographic, lifestyle, and clinical factors associated with response to biologic drug therapy in psoriatic patients. We found that age, gender, ethnicity, alcohol consumption, smoking, geographic location, age at diagnosis, duration and severity of psoriasis, and baseline C-reactive protein levels did not consistently affect response to biologic psoriasis therapy. However, increased body mass index (BMI) appears to adversely affect responses. It might therefore be valuable to include BMI as a stratification variable in future studies of psoriasis therapies and to consider a patients weight or BMI when selecting a systemic psoriasis treatment.

Quality of life results from the phase 3 REVEL randomized clinical trial of ramucirumab-plus-docetaxel versus placebo-plus-docetaxel in advanced/metastatic non-small cell lung cancer patients with progression after platinum-based chemotherapy

OBJECTIVES REVEL demonstrated that ramucirumab+docetaxel (RAM+DTX) improved overall survival, progression-free survival, and objective response rate in patients with advanced/metastatic non-small cell lung cancer with progression after platinum-based chemotherapy. This analysis examined quality of life (QoL) as assessed by the Lung Cancer Symptom Scale (LCSS) and clinician-reported functional status. MATERIALS AND METHODS The LCSS includes 6 symptom and 3 global items measured on a 0-100-mm scale; higher scores represent greater symptom burden. LCSS and ECOG PS data were collected at baseline, every 3-week cycle, the summary visit, and at the 30-day follow-up. LCSS total score and Average Symptom Burden Index (ASBI) were calculated. The primary analysis compared time to deterioration (TtD) between treatment arms for all individual items and summary scores, defined as increase from baseline by ≥ 15 mm using the Kaplan-Meier method and Cox regression. TtD to ECOG PS ≥ 2 was analyzed. RESULTS There were 1253 patients randomized to receive RAM+DTX or placebo+docetaxel (PL+DTX). Across all assessments, LCSS compliance was approximately 75% and balanced across arms. The mean (SD) baseline LCSS total score was 27.3mm (17.08 mm) on RAM+DTX and 29.6mm (17.59 mm) on PL+DTX. At 30-day follow-up, mean (SD) LCSS total score was 32.0 (19.03) on RAM+DTX and 32.5 (19.87) on PL+DTX. The TtD for all LCSS scores was similar between treatment arms. Stratified HRs (95% CI) for LCSS total score and ASBI were HR=0.99 (0.81, 1.22), p=0.932 and HR=0.93 (0.75, 1.15), p=0.514 with approximately 70% of patients censored. TtD to PS ≥ 2 was similar between treatment arms (HR=1.03 [95% CI: 0.85, 1.26], p=0.743) with approximately two-thirds of the patients censored. CONCLUSION In addition to improvement of clinical efficacy outcomes demonstrated in REVEL, these results suggest that adding ramucirumab to docetaxel did not impair patient QoL, symptoms, or functioning.

Review of treatment response in rheumatoid arthritis: assessment of heterogeneity.

Abstract Objective: Rheumatoid arthritis (RA) is a chronic, systemic, progressive, inflammatory disorder. The primary goals of treatment in RA are to reduce the signs and symptoms of disease, prevent progression of joint damage and improve patients’ physical function. Patients with different sociodemographic characteristics, varying degrees of severity of illness, and comorbidities tend to exhibit differential response to treatment. The purpose of this review was to identify a broad set of factors that are associated with and/or predictive of RA treatment response and determine those that warrant further research. Research design and methods: A comprehensive review of the literature from the last 10 years was performed using three key databases (PubMed, EMBASE, and Cochrane). All relevant articles that met the inclusion/exclusion criteria were selected and scored for their levels of evidence using the National Institute of Clinical Excellence (NICE) scoring method. Data on study design, interventions and treatment outcomes were abstracted using a structured abstraction table. Results: A total of 30 articles were included in the review and data abstraction. Besides gender, baseline clinical variables such as C-reactive protein level, erythrocyte sedimentation rate, measures of disease activity, and Health Assessment Questionnaire scores (based on five patient-centered dimensions) were consistently associated with treatment response over time. Conclusions: This comprehensive literature review identified several factors associated with treatment response which might be valuable to include as relevant measures in future studies of RA treatment. Inclusion of these factors, particularly those in the clinical and sociodemographic domains, in the design of future trials will further the understanding that ultimately may help clinicians deliver targeted treatment to community practice RA patients, thus resulting in improved patient outcomes.

A comprehensive review of predictive and prognostic composite factors implicated in the heterogeneity of treatment response and outcome across disease areas

Aim:  To assess and present the current body of evidence regarding composite measures associated with differential treatment response or outcome as a result of patient heterogeneity and to evaluate their consistency across disease areas.

Glioblastoma treatment patterns, survival, and healthcare resource use in real-world clinical practice in the USA.

Background: Glioblastoma (GB) treatment remains challenging because of recurrence and poorly defined treatment options after first-line therapy. To better understand real-world application of treatment paradigms and their impact on outcomes, we describe patterns of treatment, outcomes, and use of cancer-related healthcare resource for glioblastoma in the USA. Methods: A retrospective, online chart-abstraction study was conducted; each participating oncologist contributed ≤5 charts. Patients were ≥18 years with biopsy-confirmed primary or secondary newly diagnosed GB on or after 1 January 2010, had received first- and second-line therapies, and had information collected for ≥3 months after initiation of second-line therapy or until death. Assessments were descriptive and included Kaplan– Meier analyses from initiation to end of second-line therapy, disease progression, or death. Results: One hundred sixty physicians contributed information on 503 patient charts. During first-line therapy, patients most commonly underwent temozolomide monotherapy (76.5%). During second-line therapy, patients most commonly underwent bevacizumab monotherapy (58.1%). Median duration of second-line therapy was 130 days; median time to disease progression was 113 days. Median survival was 153 days. Use of supportive care was observed to be numerically higher in first- compared with second-line therapy except for anti-depressants, growth factors, and stimulants. Frequently used resources included corticosteroids (78.8% of patients in first-line and 62.6% in second-line therapies), anti-epileptics (45.8% and 41.5%) and narcotic opioids (45.3% and 41.4%). Conclusions: Most GB patients received temozolomide during first-line therapy and bevacizumab monotherapy or combination therapy during second-line therapy. Use of supportive care appeared to be higher in first- compared with second-line therapy for some agents.

Treatment patterns in patients with advanced gastric cancer in Taiwan

To describe treatment patterns, outcomes and healthcare resource use in patients with metastatic and/or locally recurrent, unresectable gastric cancer (MGC) in Taiwan.

Real-World Treatment Patterns among Patients with Advanced Gastric Cancer in South Korea

Purpose The purpose of this study was to understand patient treatment patterns, outcomes, and healthcare resource use in cases of metastatic and/or locally recurrent, unresectable gastric cancer (MGC) in South Korea. Materials and Methods Thirty physicians reviewed charts of eligible patients to collect de-identified data. Patients must have received platinum/fluoropyrimidine first-line therapy followed by second-line therapy or best supportive care, had no other primary cancer, and not participated in a clinical trial following MGC diagnosis. Data were summarized using descriptive statistics. Kaplan-Meier analysis was used to describe survival. Results Of 198 patients, 73.7% were male, 78.3% were diagnosed with MGC after age 55 (mean, 61.3 years), and 47.0% were current or former smokers. The majority of tumorswere located in the antrum/pylorus (51.5%). Metastatic sites most often occurred in the peritoneum (53.5%), lymph nodes (47.5%), and liver (38.9%). At diagnosis, the mean Charlson comorbidity indexwas 0.4 (standard deviation, 0.6). The most common comorbidities were chronic gastritis (22.7%) and cardiovascular disease (18.7%). Most patients (80.3%) received second-line treatment. Single-agent fluoropyrimidine was reported for 22.0% of patients, while 19.5% were treated with irinotecan and a fluoropyrimidine or platinum agent. The most common physician-reported symptoms during second-line treatment were nausea/vomiting (44.7%) and pain (11.3%), with antiemetics (44.7%), analgesics (36.5%), and nutritional support (11.3%) most often used as supportive care. Two-thirds of inpatient hospitalizations were for chemotherapy infusion. Outpatient hospitalization (31.6%) and visits to the oncologist (58.8%) were common among second-line patients. Conclusion Most patients received second-line treatment, although regimens varied. Understanding MGC patient characteristics and treatment patterns in South Korea will help address unmet needs.

An exploratory subgroup analysis of race and gender in squamous cancer of the head and neck: Inferior outcomes for African American males in the LORHAN database

OBJECTIVES Previous retrospective analyses show poor outcomes for African American (AA) patients with head and neck carcinoma (HNC). Such racial disparities are not well understood, and generally studies have been too small to investigate subgroups and interactions related to race. MATERIALS AND METHODS The longitudinal oncology registry of head and neck carcinoma registry was used to identify patients ⩾18 years of age with squamous cell carcinoma of the head and neck, with no baseline metastases, and with an adequate record of survival time. Patient demographic and treatment characteristics were evaluated as a function of race and other known potential confounders of outcome. Associations between patient characteristics, including smoking, stage, performance status, and overall survival (OS) and progression-free survival (PFS) outcomes were also examined. RESULTS Analysis of OS and PFS confirmed prior reports of inferior outcomes in AA patients vs. Whites with median OS/3-yr rate 41.7 mo/52% in AAs vs. 56.6 mo/70% in Whites (hazard ratio: 1.69 [95% confidence interval: 1.42, 2.01]). The elevated risk for worse OS and PFS in AAs remained, after multivariate adjustment. African American males incurred most of the excess risk compared to AA females. CONCLUSION This exploratory study confirmed a worse OS and PFS prognosis for AA patients, and it documents that most of the excess risk occurs in AA males. Future studies should confirm these findings and should investigate biological and other factors that account for such profound differences in outcomes.

Outcomes in patients with aggressive or refractory disease from REVEL: A randomized phase III study of docetaxel with ramucirumab or placebo for second-line treatment of stage IV non-small-cell lung cancer

OBJECTIVES The REVEL study demonstrated improved efficacy for patients with advanced non-small cell lung cancer treated with ramucirumab plus docetaxel, independent of histology. This exploratory analysis characterized the treatment effect in REVEL patients who were refractory to prior first-line treatment. MATERIALS AND METHODS Refractory patients had a best response of progressive disease to first-line treatment. Endpoints included overall survival (OS), progression-free survival (PFS), objective response rate (ORR), quality of life (QoL), and safety. Kaplan-Meier and Cox proportional hazards regression were performed for OS and PFS, and Cochran-Mantel-Haenszel test was used for response. QoL was assessed with the Lung Cancer Symptom Scale. Sensitivity analyses were performed on subgroups of the intent-to-treat population with limited time on first-line therapy. RESULTS Of 1253 randomized patients in REVEL, 360 (29%) were refractory to first-line treatment. Baseline characteristics were largely balanced between treatment arms. In the control arm, median OS for refractory patients was 6.3 versus 10.3 months for patients not meeting this criterion, demonstrating the poor prognosis of refractory patients. Median OS (8.3 vs. 6.3 months; HR, 0.86; 95% CI, 0.68-1.08), median PFS (4.0 vs. 2.5 months; HR, 0.71; 95% CI, 0.57-0.88), and ORR (22.5% vs. 12.6%) were improved in refractory patients treated with ramucirumab compared to placebo, without new safety concerns or further deteriorating patient QoL. CONCLUSIONS The effect of ramucirumab in refractory patients is similar to that in the intent-to-treat population. The benefit/risk profile for refractory patients suggests that ramucirumab plus docetaxel is an appropriate treatment option even in this difficult-to-treat population.