Factors associated with insufficient response to acute treatment of migraine in Japan: analysis of real-world data from the Adelphi Migraine Disease Specific Programme.

BACKGROUND: Real-world data on sufficient/insufficient response, and predictors of insufficient response, to acute treatments for migraine are limited in Japan. This study aimed to identify factors associated with insufficient response to acute treatment of migraine by exploring significant differences between people with migraine who sufficiently/insufficiently respond to prescribed acute treatment in Japan. METHODS: This was a retrospective analysis of 2014 Adelphi Migraine Disease Specific Programme cross-sectional survey data collected from physicians and their consulting adult patients with migraine in Japan. Insufficient responders to prescribed acute treatment were patients who achieved headache pain freedom within 2 h of acute treatment in no more than three of their last five migraine attacks. Factors associated with insufficient response to prescribed acute migraine treatment were identified using backward logistic regression. RESULTS: Overall, 227/538 (42.2%) patients were classified as insufficient responders to prescribed acute migraine treatment. Significantly more insufficient responders than sufficient responders had consulted a neurologist or a migraine/headache specialist, and had chronic migraine or medication-overuse or tension-type headaches (p < 0.05). More insufficient responders than sufficient responders reported taking acute treatment when/after the pain started (77.0 vs. 68.9%) than at first sign of migraine (p < 0.05). Compared with sufficient responders, insufficient responders reported a significantly higher mean ± standard deviation (SD) Migraine Disability Assessment total score (12.7 ± 23.3 vs. 5.8 ± 10.4, p < 0.001) and lower quality of life (EuroQol-5 Dimensions utility score 0.847 ± 0.19 vs. 0.883 ± 0.16, p = 0.024). Factors significantly associated with insufficient response to acute treatment included seeing a neurologist versus an internist (odds ratio [OR] 1.93; 95% confidence interval [CI] 1.29-2.88; p = 0.002), taking acute medication when/after pain started versus at first sign of migraine (OR 1.65; 95% CI 1.05-2.60; p = 0.030), a higher MIDAS total score (OR 1.04; 95% CI 1.02-1.06; p < 0.001), and presence of comorbid cardiovascular disease (OR 0.53; 95% CI 0.28-0.98; p = 0.044). CONCLUSIONS: Many people with migraine in Japan struggle to adequately treat migraine attacks with prescribed acute medication and exhibit high levels of unmet need for acute treatment. Optimized management strategies utilizing existing therapeutic options as well as additional effective therapeutic options for migraine are required to improve symptoms and quality of life.

Prevalence, burden, and clinical management of migraine in China, Japan, and South Korea: a comprehensive review of the literature.

BACKGROUND: The objective of this review was to determine the unmet needs for migraine in East Asian adults and children. METHODS: We searched MEDLINE and EMBASE (January 1, 1988 to January 14, 2019). Studies reporting the prevalence, humanistic and economic burden, and clinical management of migraine in China (including Hong Kong and Taiwan), Japan, and South Korea were included. Studies conducted before 1988 (before the International Headache Society [IHS] first edition of the International Classification of Headache Disorders) were not included. RESULTS: We retrieved 1337 publications and 41 met the inclusion criteria (28 from China, 7 from Japan, and 6 from South Korea). The 1-year prevalence of migraine (IHS criteria) among adults ranged from 6.0% to 14.3%. Peak prevalence ranged from 11% to 20% for women and 3% to 8% for men (30- to 49-year-olds). For children, prevalence of migraine increased with age. Information on the economic burden and clinical management of migraine was limited, particularly for children. When reported, migraine was significantly associated with high levels of disability and negative effects on quality of life. Studies suggested low levels of disease awareness/diagnosis within each country. Of individuals with migraine from China, 52.9% to 68.6% had consulted a physician previously, 37.2% to 52.7% diagnosed with headache had not been diagnosed with migraine previously, and 13.5% to 18% had been diagnosed with migraine previously. Of individuals with migraine from Japan, 59.4% to 71.8% had never consulted a physician previously, 1.3% to 7.3% regularly consulted physicians for their headache, and only 11.6% of individuals with migraine were aware that they had migraine. In addition, studies suggested that over-the-counter medication use was high and prescription medication use was low in each country. CONCLUSIONS: This review suggests that there are unmet needs for migraine in terms of sufficient and appropriate diagnosis, and better management and therapies for treatment of migraine in East Asia. The findings are limited by a lack of recent information and significant gaps in the literature. More recent, population-based studies assessing disease burden and clinical management of migraine are needed to confirm unmet needs for migraine across East Asia.

Clinical effectiveness and clinical toxicity associated with platinum-based doublets in the first-line setting for advanced non-squamous non-small cell lung cancer in Chinese patients: a retrospective cohort study.

BACKGROUND: Real-world evidence lacks for clinical effectiveness and clinical toxicity associated with platinum-based doublets in the first-line setting for advanced non-squamous non-small cell lung cancer (advNS-NSCLC) in Chinese patients. METHODS: Patients receiving first-line chemotherapy for advNS-NSCLC in four Chinese tertiary care hospitals from 2007 to 2012 were retrospectively identified for chart review. Propensity score methods created best matched pairs for platinum/pemetrexed versus other platinum-based doublets for head-to-head comparisons of early treatment discontinuation (completed treatment cycles <4), treatment failure (progressive disease or early treatment discontinuation), and adverse events (AE). Conventional multiple logistic regression analyses were also performed to confirm the impact of the studied platinum-based doublets on early treatment discontinuation, treatment failure, and hematological AE using vinorelbine/platinum as reference. RESULTS: 1,846 patients were included to create propensity score matched treatment groups for platinum/pemetrexed versus docetaxel (95 pairs), paclitaxel (118 pairs), gemcitabine (199 pairs), and vinorelbine (72 pairs)-contained doublet, respectively. Platinum/pemetrexed was associated with significantly lower risks of early treatment discontinuation (odds ratio (OR) ranged from 0.239, p = 0.001 relative to platinum/docetaxel to 0.389, p = 0.003 relative to platinum/paclitaxel) and treatment failure (OR ranged from 0.257, p < 0.001 relative to platinum/paclitaxel to 0.381, p < 0.001 relative to platinum/gemcitabine) than the other four studied doublets. Platinum/pemetrexed was also associated with several significantly lower hematological AE rates, such as versus platinum/paclitaxel (any hematological AE: OR 0.508, p = 0.032), platinum/gemcitabine (i.e., any hematological AE: OR 0.383, p < 0.001; anemia: OR 0.357, p < 0.001; thrombocytopenia: OR 0.345, p < 0.001) or platinum/vinorelbine (i.e., neutropenia: OR 0.360, p = 0.046; anemia: OR 0.181, p = 0.014) in matched patients. Further conventional logistic regression analyses indicated that pemetrexed/platinum was ranked lowest for the risks of early treatment discontinuation (OR 0.326, p < 0.001), treatment failure (OR 0.460, p < 0.001), and any hematological AE (OR 0.329, p < 0.001). CONCLUSIONS: Pemetrexed plus platinum had significantly superior clinical effectiveness as compared to the other platinum-based doublets with third-generation cytotoxic agents and was also associated with several lower hematological toxicity rates than gemcitabine or vinorelbine-based doublet in the first-line setting for advNS-NSCLC in Chinese patients.

Treatment Patterns and Health Resource Utilization in Patients With HR+/ HER2- Locally Advanced or Metastatic Breast Cancer in a Real-World Setting in Taiwan.

OBJECTIVES: This study aimed to understand current treatment patterns and healthcare resource utilization (HRU) of women with locally advanced or metastatic breast cancer (advanced breast cancer [ABC]) in Taiwan overall and within the subgroup of patients who were postmenopausal women with no previous systemic therapy in the ABC setting. METHODS: A chart review of anonymized data on patient characteristics, treatment patterns, and HRU was conducted via an online physician survey including 118 patient charts from women ≥ 18 years old with hormone receptor positive/human epidermal growth receptor negative ABC, diagnosed between 2015 and 2017. RESULTS: The mean age of all patients was 56.6 years (range 29-83). Among the 118 patients, the most common first-line systemic therapy group after diagnosis of ABC was endocrine-based therapy (39.0%) or endocrine therapy (ET) plus chemotherapy (ChT) combinations (38.1%). In the postmenopausal subgroup (n = 56), ET-based therapy was the most common (44.6%). Oncologist visits, at annual rate of 9.20 (95% confidence interval 8.81-9.60), and hospitalizations, at annual rate of 1.08 (95% confidence interval 0.96-1.22), were key drivers of HRU. Of the 118 patients, the 72 with at least one ChT agent in their first-line regimen had an annual hospitalization rate of 1.4 versus 0.45 admissions compared with the 46 patients on first-line ET-based therapy. CONCLUSIONS: Current treatment patterns suggest an unmet need for new medications that lead to reduction in high rate of ChT use. Results can inform future evaluations of new ABC treatments that estimate the health economic impact of their adoption in Taiwan.

Treatment Patterns and Health Resource Utilization in Patients With Hepatocellular Carcinoma After Failure of Sorafenib in Real-World Setting in Taiwan.

OBJECTIVES: This study aimed to characterize current treatment patterns and healthcare resource utilization (HRU) observed among patients with hepatocellular carcinoma (HCC) after the failure of sorafenib in real-world setting in Taiwan. METHODS: A chart review was conducted in 130 patients; the inclusion criteria were patients with HCC who were aged 20 years or older and had received systemic therapy or best supportive care after failure of first-line systemic treatment with sorafenib between 2016 and 2018. Anonymized data on patient characteristics, treatment pathways, and survival were abstracted. RESULTS: The mean age of patients was 61.7 years (range 27-84); of these 130 patients, 103 (79%) were male, 81 (62%) had high alpha-fetoprotein (AFP) levels (≥400 ng/mL), and 96 (78.0%) were deceased at the time of data abstraction. After sorafenib therapy, 60 patients (46%) received systemic therapy, including nivolumab monotherapy (42%) and chemotherapy (25%). Oncologist visits at a semiannual per-patient rate of 3.7 (95% confidence interval [CI] 3.4-4.0) and hospitalizations at rate of 1.1 (95% CI 1.0-1.3) were the key contributors to HRU. Semiannual per-patient hospitalization rate was 1.3 (95% CI 1.1-1.5) in the high-AFP group. Median survival from discontinuation of sorafenib was 6.9 months (95% CI 5.9-9.0). CONCLUSIONS: This real-world evidence research on treatment patterns reflected substantial HRU consistent with the severity of HCC, particularly in the high-AFP group. Findings highlighted continuing high mortality in HCC, underlying a need for new treatments that can lengthen survival. Results can inform future evaluations of new HCC treatments that estimate the health economic impact of their adoption in Taiwan.

Health state utilities in non-small cell lung cancer: An international study.

AIM: Quality of life weights (utilities) are an important input in economic evaluation and evidence suggests that there can be important differences between countries. This study was designed to capture utilities for metastatic non-small cell lung cancer and common grade III/IV toxicities associated with treatment from local populations in the United Kingdom, Australia, France, China, Taiwan, and Korea. Toxicities included neutropenia, febrile neutropenia, fatigue, diarrhea, nausea and vomiting, rash, bleeding, hypertension, and hair loss. METHODS: Existing health state descriptions of non-small cell lung cancer were adapted to represent descriptions of patients on first-line treatment. Twenty-three states were translated and assessed in cognitive debrief content validation interviews with oncologists in each country. Seventy-five respondents per country completed a time trade-off interview to evaluate the states. Variation between countries for all states was explored with a Generalized Estimating Equations model. RESULTS: The mean utility for "stable disease and no side effects" (base state) varied between 0.84 (United Kingdom) and 0.54 (Taiwan). The largest utility decrements were found for febrile neutropenia (0.47) and neutropenia (0.35) across all countries. Asian countries regarded bleeds as a severe toxicity whereas non-Asian countries did not and valued diarrhea and fatigue as more severe. Significant differences in utilities between countries emerged with the Taiwanese population in particular rating states as significantly worse than other countries. CONCLUSION: This study improves our understanding of how utilities for the same states can vary across countries. The study shows the importance of capturing utilities that reflect the preferences of the local population.

Treatment patterns in patients with advanced gastric cancer in Taiwan.

AIM: To describe treatment patterns, outcomes and healthcare resource use in patients with metastatic and/or locally recurrent, unresectable gastric cancer (MGC) in Taiwan. METHODS: Patients who had received first-line therapy (platinum and/or fluoropyrimidine) followed by second-line therapy or best supportive care (BSC) only were eligible. Participating physicians provided de-identified information from patient charts. Data were summarized descriptively and Kaplan-Meier analysis was used to describe time to events. RESULTS: Overall, 37 physicians contributed 122 patient charts. Of the 122 patients (median age, 61 years; 62% male), 43 (35%) received BSC only following first-line therapy, whereas 79 (65%) received second-line therapy. There was heterogeneity in second-line treatment, although fluoropyrimidine with or without a platinum agent was most frequently used. Median survival was 12.5 (interquartile range [IQR], 8.2-20.8) months from MGC diagnosis for patients receiving second-line therapy and 8.0 (IQR, 5.6-not reached) months for patients receiving BSC only. The most common treatment-related symptoms were nausea/vomiting (58%); the most common cancer-related symptoms were pain (61%), ascites (35%) and nausea/vomiting (33%). Inpatient and outpatient hospitalizations were numerically more common for patients receiving second-line therapy than for those receiving BSC only; the prevalence of hospice and skilled nursing facility stays were numerically more common for patients receiving BSC only. CONCLUSIONS: In this Taiwanese MGC population, 65% received active second-line therapy with heterogeneity seen in the regimen used. Clinical outcomes suggest an unmet medical need in this population. This study may help inform clinical practice and future research to ultimately improve patient outcomes 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.

Utilities for Type 2 Diabetes Treatment-Related Attributes in a South Korean and Taiwanese Population.

OBJECTIVES: To elicit utilities associated with type 2 diabetes medication-related attributes from South Korean and Taiwanese populations and to identify key drivers of preferences. METHODS: Data from 59 respondents from the general population in South Korea and Taiwan were analyzed. Respondents' preferences were elicited using a paper-based standard gamble questionnaire. Health states were designed to identify the utility or disutility of type 2 diabetes medication-related attributes, including dose frequency, nausea/vomiting (hereafter referred to as nausea), and weight change. RESULTS: The mean utility for the basic health state (encompassing current body weight and no nausea) was 0.754 ± 0.155 with weekly dose administration. Respondents showed a preference for weekly over daily administration (average increase in utility of 0.043 across all health states with weekly, vs. daily, administration). Nausea was associated with a decrease in utility (average decrease of -0.034 across all health states with, vs. without, nausea). Weight gain had little effect on utility (average decrease of 0.000 and 0.001 across all health states with, vs. without, 3% and 5% gain, respectively), although weight loss was associated with a small increase in utility (average increase of 0.028 and 0.029 across all health states with, vs. without, 3% and 5% loss, respectively). CONCLUSIONS: Utilities associated with type 2 diabetes medication-related attributes were elicited from a general population sample from South Korea and Taiwan. Treatment-related attributes, in particular dose frequency and nausea, had a measurable effect on utility and should be considered when selecting treatment regimens for South Korean or Taiwanese patients with type 2 diabetes.

First-Line Pemetrexed Plus Cisplatin Followed by Gefitinib Maintenance Therapy Versus Gefitinib Monotherapy in East Asian Never-Smoker Patients With Locally Advanced or Metastatic Nonsquamous Non-Small-cell Lung Cancer: Quality of Life Results From a Randomized Phase III Trial.

BACKGROUND: The efficacy results from an open-label, randomized, multicenter study found no significant difference in progression-free survival between pemetrexed plus cisplatin followed by maintenance gefitinib (PC/G) and gefitinib monotherapy (G) in patients with advanced nonsquamous non-small-cell lung cancer (NSCLC) and unknown epidermal growth factor receptor (EGFR) mutation status (hazard ratio favored PC/G). The present report describes the quality of life (QoL) results from that trial. PATIENTS AND METHODS: Chemotherapy-naive, East Asian, light ex-smokers or never-smokers with advanced nonsquamous NSCLC and unknown EGFR mutation status (n = 236) were randomly assigned (1:1) to PC/G or G. EGFR mutation status was subsequently determined for 74 patients. The symptoms and QoL were assessed using the Lung Cancer Symptom Scale (LCSS). The time to worsening of symptoms (TWS) was analyzed using the Kaplan-Meier method. RESULTS: In the overall population, the TWS was generally longer in the G group (n = 109) than in the PC/G group (n = 109) for the LCSS symptoms classified as treatment-related (loss of appetite, fatigue) and tumor-related (cough, dyspnea, hemoptysis, pain). In the subgroup of patients with wild-type EGFR, the TWS was generally longer in the PC/G group (n = 13) than in the G group (n = 8) for the tumor-related LCSS symptoms. CONCLUSION: In this study population clinically selected to respond to gefitinib, the LCSS scores were more favorable in the G group than in the PC/G group. Patients with wild-type EGFR tended to show greater improvement in tumor-related LCSS symptoms with chemotherapy than with gefitinib alone. These LCSS outcomes provide further evidence that patients with wild-type EGFR might not benefit from first-line treatment of advanced NSCLC with gefitinib.

Real-world hospital costs for nonchemotherapy drugs and nondrug care associated with platinum-based doublets in the first-line setting for advanced nonsquamous non-small-cell lung cancer in Chinese patients: a retrospective cohort study.

OBJECTIVE: The objective of this study was to compare hospital costs per treatment cycle (HCTC) for nonchemotherapy drugs and nondrug care associated with platinum-based doublets in the first-line setting for advanced nonsquamous non-small-cell lung cancer (AdvNS-NSCLC) in Chinese patients. METHODS: Patients receiving platinum-based doublets in the first-line setting for AdvNS-NSCLC from 2010 to 2012 in two Chinese tertiary hospitals were identified to create the retrospective study cohort. Propensity score methods were used to create matched treatment groups for head-to-head comparisons on HCTC between pemetrexed-platinum and other platinum-based doublets. Multiple linear regression analyses were performed to rank studied platinum-based doublets for their associations with the log10 scale of HCTC for nonchemotherapy drugs and nondrug care. RESULTS: Propensity score methods created matched treatment groups for pemetrexed-platinum versus docetaxel-platinum (61 pairs), paclitaxel-platinum (39 pairs), gemcitabine-platinum (93 pairs), and vinorelbine-platinum (73 pairs), respectively. Even though the log10 scale of HCTC for nonchemotherapy drugs and nondrug care associated with pemetrexed-platinum was ranked lowest in all patients (coefficient -0.174, P=0.015), which included patients experiencing any hematological adverse events (coefficient -0.199, P=0.013), neutropenia (coefficient -0.426, P=0.021), or leukopenia (coefficient -0.406, P=0.001), pemetrexed-platinum had the highest total HCTC (median difference from RMB 1,692 to RMB 7,400, P<0.001) among platinum-based doublets because of its higher drug acquisition costs (median difference from RMB 4,636 to RMB 7,332, P<0.001). CONCLUSION: Among Chinese patients receiving platinum-based doublets in the first-line setting for AdvNS-NSCLC, the higher acquisition costs for nonplatinum cytotoxic drugs associated with pemetrexed-platinum could be partially offset by its significantly lower hospital costs for nonchemotherapy drugs and nondrug care.

Cost Analyses in the US and Japan: A Cross-Country Comparative Analysis Applied to the PRONOUNCE Trial in Non-Squamous Non-Small Cell Lung Cancer.

INTRODUCTION: Health technology assessment is not required for regulatory submission or approval in either the United States (US) or Japan. This study was designed as a cross-country evaluation of cost analyses conducted in the US and Japan based on the PRONOUNCE phase III lung cancer trial, which compared pemetrexed plus carboplatin followed by pemetrexed (PemC) versus paclitaxel plus carboplatin plus bevacizumab followed by bevacizumab (PCB). METHODS: Two cost analyses were conducted in accordance with International Society For Pharmacoeconomics and Outcomes Research good research practice standards. Costs were obtained based on local pricing structures; outcomes were considered equivalent based on the PRONOUNCE trial results. Other inputs were included from the trial data (e.g., toxicity rates) or from local practice sources (e.g., toxicity management). The models were compared across key input and transferability factors. RESULTS: Despite differences in local input data, both models demonstrated a similar direction, with the cost of PemC being consistently lower than the cost of PCB. The variation in individual input parameters did affect some of the specific categories, such as toxicity, and impacted sensitivity analyses, with the cost differential between comparators being greater in Japan than in the US. CONCLUSION: When economic models are based on clinical trial data, many inputs and outcomes are held consistent. The alterable inputs were not in and of themselves large enough to significantly impact the results between countries, which were directionally consistent with greater variation seen in sensitivity analyses. The factors that vary across jurisdictions, even when minor, can have an impact on trial-based economic analyses. FUNDING: Eli Lilly and Company.

Supportive Care Costs Associated with Second-Line Chemotherapy in Chinese Patients with Advanced Non-Squamous Non-Small Cell Lung Cancer: A Retrospective Cohort Study.

PURPOSE: To compare supportive care costs associated with second-line chemotherapy for advanced non-squamous non-small cell lung cancer (advNS-NSCLC) in Chinese patients. METHODS: This retrospective cohort study included patients receiving pemetrexed or docetaxel-based second-line chemotherapy for advNS-NSCLC in four Chinese hospitals from 2007 to 2012. The best matched pairs between pemetrexed and other regimens were identified using propensity score methods for head-to-head comparisons of supportive care costs per treatment cycle. Linear regression analyses were performed to rank log10 scale of supportive care costs per treatment cycle associated with chemotherapy by tumor response and hematologic toxicity. RESULTS: 384 patients were included to create propensity score-matched treatment groups for pemetrexed singlet versus docetaxel singlet, platinum/pemetrexed, and platinum/docetaxel, respectively. Pemetrexed singlet was associated with significantly less supportive care costs per treatment cycle than the two doublets (platinum/pemetrexed: median difference -RMB 9,877, p = 0.003; platinum/docetaxel: median difference -RMB 8,370, p = 0.009; 1 RMB = 0.16 USD) but not docetaxel singlet in matched patients. Of the four studied chemotherapy regimens, pemetrexed singlet was associated with the lowest log10 scale of supportive care costs per treatment cycle in patients with tumor control (coefficient relative to docetaxel singlet -1.049, p < 0.001) or leukopenia (coefficient relative to docetaxel singlet -0.991, p = 0.034). CONCLUSION: Pemetrexed singlet cost significantly less for supportive care than pemetrexed or docetaxel-based doublets when treating Chinese patients with AdvNS-NSCLC in the second-line setting. Pemetrexed singlet was also associated with significantly less supportive care costs per treatment cycle than docetaxel singlet in patients with tumor control or leukopenia.

Health state utility values associated with advanced gastric, oesophageal, or gastro-oesophageal junction adenocarcinoma: a systematic review.

OBJECTIVES: To systematically identify utility values associated with advanced gastric cancer (GC), oesophageal cancer (OC), or gastro-oesophageal junction (GEJ) cancer. Utility values relating to health states are an essential component for cost-utility analysis (CUA). METHODS: MEDLINE, Embase, Cochrane Library, and EconLit databases were reviewed for relevant studies using a pre-defined search strategy. Studies eligible for inclusion reported health state utility values (HSUVs) using direct (standard gamble [SG] and time-trade-off [TTO]) and indirect (such as EuroQol 5D [EQ-5D], short-form 6D [SF-6D], and the 15-dimensional instrument [15D]) methods for patients with advanced GC, OC, or GEJ cancer. RESULTS: A total of 539 unique publications were identified, of which eight met the inclusion criteria (GC, n = 2; mixed population [gastrointestinal cancers], n = 4; OC, n = ). The most commonly used instrument to estimate HSUVs was the EQ-5D (n = 7). Utilities were also estimated using the SF-6D and the 15D in the same study (n = 1). Direct elicitation methods included the TTO (n = 2) and SG (n = 1). Across the eight identified publications, health states and study populations were heterogeneous and sample sizes were limited. LIMITATIONS: This review, as with all summaries of this nature, is only as robust as the data derived from the identified studies. The systematic review process does not resolve any design issues or biases associated with the original studies. CONCLUSIONS: Limited data estimate HSUVs in patients with advanced GC, OC, or GEJ cancer. Utilities for advanced GC alone and advanced OC alone were reported in only two publications for each cancer type. No publications considered advanced GEJ utilities alone, and four publications considered utilities for a mixed population of gastrointestinal cancer types. Comparisons are confounded by heterogeneity across the identified publications. Further research into HSUVs associated with advanced GC and OC is required to improve the evidence available for use in CUAs.

Prognostic factors for patients with advanced non-small cell lung cancer treated with gemcitabine-platinum as first-line therapy in an observational setting in China.

BACKGROUND: This study examined the prognostic factors associated with survival in advanced non-small cell lung cancer (NSCLC) patients receiving gemcitabine-platinum regimens as first-line therapy in real-world clinical settings in China. METHODS: Data was analyzed from a multinational, prospective, non-interventional, observational study of individuals receiving gemcitabine-platinum regimens as first-line therapy for NSCLC, focusing on 300 patients from mainland China. A Cox regression model was used to determine the association of 38 prognostic factors, including patient smoking characteristics, with overall survival. RESULTS: In these 300 patients, the mean age was 58.9 (±10.8) years, with males comprising 71% of the population. Thirty percent of patients had an Eastern Cooperative Oncology Group performance status (PS) of 0 and 70% had a PS of 1. The majority of patients had NSCLC of adenocarcinoma origin (57%). Multivariate Cox regression analyses adjusted for baseline factors revealed that gender, tumor (T) staging, metastasis (M) staging, liver metastases, serum albumin, and superior vena cava obstruction were significant prognostic factors. Smoking during therapy was not significantly associated with survival, although numbers were small for this variable (n = 16). Weight loss of >10% was a significant prognostic factor for adverse events. CONCLUSIONS: Gender, T staging, M staging, liver metastases, superior vena cava obstruction, and serum albumin are prognostic factors affecting overall survival in mainland Chinese patients receiving first-line gemcitabine-platinum regimens for advanced NSCLC. These negative prognostic factors may warrant further investigation in clinical trials.

Tumor response and clinical toxicity associated with second-line chemotherapy regimens for advanced non-squamous non-small cell lung cancer: A retrospective cohort study.

BACKGROUND: Previously reported superior tumor response of pemetrexed in the second-line setting for advanced non-squamous non-small cell lung cancer (advNS-NSCLC) has never been confirmed in real-world studies. Platinum-based doublet is frequently used in the second-line setting for advanced NSCLC in China. METHODS: A retrospective cohort study was conducted including patients receiving pemetrexed or docetaxel-based chemotherapy in the second-line setting for advNS-NSCLC in four Chinese tertiary care hospitals. Propensity score matched treatment groups were created for head-to-head comparisons on best tumor response and clinical toxicity. Multiple regression analyses were performed to rank the impact of the four regimens on the risks of tumor progression and hematological adverse events. RESULTS: Three hundred and eighty-four patients were included for creating matched treatment groups for pemetrexed versus platinum/pemetrexed (33 pairs), docetaxel (17 pairs), and platinum/docetaxel (29 pairs), respectively. No significant differences were identified for best tumor response between pemetrexed and the other three regimens. However, pemetrexed was associated with significantly fewer patients experiencing anemia (39.4% vs. 69.7%, P = 0.004) and neutropenia (6.1% vs. 30.3%, P = 0.021) than platinum/pemetrexed. Multiple regression analyses indicated that pemetrexed was associated with significantly slower tumor progression (hazard ratio 0.628, P = 0.040) and a significantly lower risk of neutropenia (odds ratio 0.132, P = 0.019) than docetaxel. CONCLUSIONS: Pemetrexed was associated with significantly postponed tumor progression and significantly less hematological toxicity than docetaxel in the real-world second-line setting for advNS-NSCLC in Chinese patients. Pemetrexed monotherapy had comparable tumor response, but significantly less hematological toxicity than pemetrexed-based doublet.

A systematic review of the interobserver variability for histology in the differentiation between squamous and nonsquamous non-small cell lung cancer.

INTRODUCTION: The importance of identifying non-small cell lung cancer (NSCLC) histologic subtype has increased recently because of the development of target-specific chemotherapeutic agents. This systematic review was undertaken to examine the interobserver variability for histology in differentiating between subtypes of NSCLC, specifically the ability to differentiate squamous from nonsquamous histology. METHODS: A systematic literature search was undertaken to identify studies that evaluated the reproducibility of histologic diagnosis by pathologists in their reporting of NSCLC subtypes. Studies were screened using a priori defined eligibility criteria. The National Health and Medical Research Council diagnostic levels of evidence were applied and quality assessed using the Quality Assessment of Diagnostic Accuracy Studies tool. Data were extracted and reanalyzed to permit comparison of agreement in nonsquamous and squamous cell carcinoma by 2 × 2 tables. Percentage agreement and kappa statistics were calculated for each included study. RESULTS: Out of 1480 articles identified through the literature search, six were eligible for inclusion. The percentage agreement for all subtypes of NSCLC in the included studies ranged from 67.1 to 89.6% (κ, 0.42-0.84). Based on the primary reanalysis of data (reanalysis 1), agreement between pathologists in differentiating nonsquamous and squamous histology ranged from 77.0 to 94.2% (κ = 0.48-0.88) indicating a moderate to high level of agreement. CONCLUSION: The reasonably high agreement and kappa statistics for the included studies suggest that pathologists can reproducibly differentiate between nonsquamous and squamous NSCLC. This is clinically important in guiding oncologist decision making in choosing the most appropriate therapy for their patients.