Cost-effectiveness analysis of durvalumab plus etoposide: platinum in the first-line therapy of extensive stage small-cell lung cancer from the Chinese payers' perspective.

INTRODUCTION: Results from the CASPIAN trial (Durvalumab ± Tremelimumab in Combination With Platinum Based Chemotherapy in Untreated Extensive-Stage Small Cell Lung Cancer) trial demonstrated the clinical benefit of durvalumab plus etoposide-platinum (EP) chemotherapy as first-line treatment for patients with extensive stage small-cell lung cancer (ES-SCLC). However, considering the high price of durvalumab, it is unclear whether addition of durvalumab to EP chemotherapy has economic value compared with EP alone. In this study, we aimed to evaluate the cost-effectiveness of durvalumab plus EP chemotherapy as a first-line treatment for patients with ES-SCLC. METHODS: A Markov model comprising three health states (stable, progressive, and dead) was developed to simulate the process of small-cell lung cancer. Utility and costs were obtained from published resources. Health outcomes were derived from the CASPIAN trial. Costs were calculated based on the standard medical fees in Zhejiang Province from Chinese patients' perspective. Utility values were obtained from published data. One-way and probabilistic sensitivity analyses were applied to verify model robustness. RESULTS: The addition of durvalumab to EP chemotherapy costs more than $32,220, with a gain of 0.14 quality-adjusted life years (QALYs) compared with EP alone. The incremental cost-effective ratio was $230,142.9 per QALY, which exceeds the willingness to pay threshold of $28,527 per QALY. In the sensitivity analysis, the utility values for the progressive state, costs of durvalumab and EP chemotherapy, and costs for the progressive state were considered to be the three most sensitive factors in the model. CONCLUSION: The addition of durvalumab to EP chemotherapy is not a cost-effective strategy in the first-line therapy of ES-SCLC from the Chinese payers' perspective.

Economic analyses of immune-checkpoint inhibitors to treat lung cancer.

Introduction: Total lung-cancer-management costs are increasing dramatically. The widespread use of immune-checkpoint inhibitors (ICIs) explains this rise in large part and financially impacts healthcare systems. Economic assessment has been adapted to this new challenge.Areas covered: This review provides an overview of the economic literature on the use of ICIs to treat lung cancer. Numerous papers have been published over the last few years. Cancers analyzed were non-squamous non-small-cell lung cancer (NSCLC), squamous NSCLC, locally advanced NSCLC, or small-cell lung cancer.Expert commentary: For the majority of patients, ICIs are cost-effective for lung cancer management. However, these results are influenced by the threshold chosen by each of the different countries. Patient selection, treatment duration, and factors predictive of efficacy are mandatory to decrease costs.

Disparities in the use of stereotactic radiosurgery for the treatment of lung cancer brain metastases: a SEER-Medicare study.

Stereotactic radiosurgery (SRS) is a costly procedure used to irradiate disease tissue while sparing healthy tissue, ideally limiting the side effects of treatment. SRS is frequently used in the setting of lung cancer, which is associated with greater rates of BM, though its cost may lead to potentially inequitable use across patient populations. This study investigates potential disparities in the use of SRS to treat Medicare patients. Surveillance, Epidemiology, and End-Results cancer registry data for patients diagnosed between the years 2010 and 2012 were examined to identify lung cancer patients diagnosed with BM at the same time as their primary cancer (SBM). Medicare claims for SRS were identified; the odds of having SRS claims and hazards of mortality associated with those odds were examined with respect to various clinical and demographic characteristics. Of 74,142 Medicare-enrolled patients diagnosed with lung cancer, 9192 were diagnosed with SBM and 3259 of those patients received SRS. Adjusting for clinical and demographic characteristics, males with SBM had 0.85 times the odds of SRS compared to females with SBM. Black patients and those of other race had significantly lower odds of evidence of SRS compared to WNH patients. SRS may not be delivered equitably among Medicare patients. Males and minority patients may have decreased odds of SRS and worse survival compared to female and WNH patients, respectively.

Cost-effectiveness analysis of atezolizumab plus chemotherapy in the first-line treatment of extensive-stage small-cell lung cancer.

OBJECTIVES: A double-blind, placebo-controlled, phase 3 trial has shown atezolizumab plus chemotherapy in the first-line treatment of extensive-stage small-cell lung cancer could significantly prolong overall survival and progression-free survival than chemotherapy alone. This study aimed to assess the cost-effectiveness of atezolizumab plus chemotherapy as first-line treatment for patients with extensive-stage small-cell lung from an American perspective. MATERIALS AND METHODS: Basic medical information was derived from the double-blind, placebo-controlled, phase 3 trial (IMpower133, NCT02763579). A Markov model was developed to simulate the process of small-cell lung cancer, including three health states: progression-free survival (PFS), progressive disease (PD), and death. Utilities and costs were obtained from published resources. Sensitivity analyses were applied to explore the impact of essential variables. RESULTS: Treatment with atezolizumab plus chemotherapy was estimated to increase costs by $52,881compared with chemotherapy alone, with a gain of 0.10 quality adjusted life years (QALYs), leading to an incremental cost-effective ratio of $528,810 per QALY. The cost of PFS state and atezolizumab were the most influential factors to the model. CONCLUSION: The combination of atezolizumab, carboplatin and etoposide is not a cost-effective choice in the first-line treatment of extensive-stage SCLC from an American perspective.

Barriers to Combined-Modality Therapy for Limited-Stage Small Cell Lung Cancer.

Importance: Combined-modality therapy with chemotherapy and radiation therapy plays a crucial role in the upfront treatment of patients with limited-stage small cell lung cancer (SCLC), but there may be barriers to utilization in the United States. Objective: To estimate utilization rates and factors associated with chemotherapy and radiation therapy delivery for limited-stage SCLC using the National Cancer Database. Design, Setting, and Participants: Analysis of initial management of all limited-stage SCLC cases from 2004 through 2013 in the National Cancer Database. Main Outcomes and Measures: Utilization rates of chemotherapy and radiation therapy at time of initial treatment. Multivariable analysis identified independent clinical and socioeconomic factors associated with utilization and overall survival. Results: A total of 70 247 cases met inclusion criteria (55.3% female; median age, 68 y [range, 19-90 y]). Initial treatment was 55.5% chemotherapy and radiation therapy, 20.5% chemotherapy alone, 3.5% radiation therapy alone, and 20.0% neither (0.5% not reported). Median survival was 18.2 (95% CI, 17.9-18.4), 10.5 (95% CI, 10.3-10.7), 8.3 (95% CI, 7.7-8.8), and 3.7 (95% CI, 3.5-3.8) months, respectively. Being uninsured was associated with a lower likelihood of both chemotherapy (odds ratio [OR], 0.65; 95% CI, 0.56-0.75; P < .001) and radiation therapy (OR, 0.75; 95% CI, 0.67-0.85; P < .001) administration on multivariable analysis. Medicare/Medicaid insurance had no impact on chemotherapy use, whereas Medicaid (OR, 0.79; 95% CI, 0.72-0.87; P < .001) and Medicare (OR, 0.86; 95% CI, 0.82-0.91; P < .001) were independently associated with a lower likelihood of radiation therapy delivery. Lack of health insurance (HR, 1.19; 95% CI, 1.13-1.26; P < .001), Medicaid (HR, 1.27; 95% CI, 1.21-1.32; P < .001), and Medicare (HR, 1.12; 95% CI, 1.09-1.15; P < .001) coverage were independently associated with shorter survival on adjusted analysis, while chemotherapy (HR, 0.55; 95% CI, 0.54-0.57; P < .001) and radiation therapy (HR, 0.62; 95% CI, 0.60-0.63; P < .001) were associated with a survival benefit. Conclusions and Relevance: Substantial proportions of patients documented in a major US cancer registry did not receive radiation therapy or chemotherapy as part of initial treatment for limited-stage SCLC, which, in turn, was associated with poor survival. Lack of radiation therapy delivery was uniquely associated with government insurance coverage, suggesting a need for targeted access improvement in this population. Additional work will be necessary to conclusively define exact population patterns, specific treatment deficiencies, and causative factors leading to heterogeneous care delivery.

Effects of symptom clusters and depression on the quality of life in patients with advanced lung cancer.

People with advanced lung cancer experience later symptoms after treatment that is related to poorer psychosocial and quality of life (QOL) outcomes. The purpose of this study was to identify the effect of symptom clusters and depression on the QOL of patients with advanced lung cancer. A sample of 178 patients with advanced lung cancer at the National Cancer Center in Korea completed a demographic questionnaire, the M.D. Anderson Symptom Inventory-Lung Cancer, the Center for Epidemiological Studies Depression Scale, and the Functional Assessment of Cancer Therapy-General scale. The most frequently experienced symptom was fatigue, anguish was the most severe symptom-associated distress, and 28.9% of participants were clinically depressed. Factor analysis was used to identify symptom clusters based on the severity of patients' symptom experiences. Three symptom clusters were identified: treatment-associated, lung cancer and psychological symptom clusters. The regression model found a significant negative impact on QOL for depression and lung cancer symptom cluster. Age as the control variable was found to be significant impact on QOL. Therefore, psychological screening and appropriate intervention is an essential part of advanced cancer care. Both pharmacological and non-pharmacological approaches for alleviating depression may help to improve the QOL of lung cancer patients.

Cost-effectiveness analysis of sensitive relapsed small-cell lung cancer based on JCOG0605 trial.

PURPOSE: Since combined strategy with cisplatin, etoposide, and irinotecan has shown the superiority to topotecan alone as second-line chemotherapy in patients with sensitive relapsed small-cell lung cancer, this study aimed to compare these two treatments based on JCOG0605 trail from Chinese cost-effectiveness perspective. METHODS: Basic medical information was derived from a multicenter, open-label, randomized phase III trial (JCOG0605). A Markov model including three health states: progression-free state, progressive disease (PD), and death, was developed to simulate the process of sensitive relapsed small-cell lung cancer. Cost was calculated from the perspective of Chinese society. Sensitivity analyses were applied to explore the impact of essential variables. RESULTS: Treatment with combination chemotherapy was estimated to increase costs by $6947.32 compared with topotecan alone, with a gain of 0.26 quality-adjusted life years (QALYs). Thus, the incremental cost-effective ratio was $26720.46/QALY for combination treatment versus monotherapy, which was beyond the threshold of 3 × the per capita GDP of China, $24423.00. The costs of PD state were the most influential factors to the model. CONCLUSION: The combination chemotherapy with cisplatin, etoposide, and irinotecan was not a cost-effectiveness choice for patients with sensitive relapsed SCLC in China from the cost-effectiveness perspective.

Clinical and Cost Implications of Universal Versus Locally Advanced-Stage and Advanced-Stage-Only Molecular Testing for Epidermal Growth Factor Receptor Mutations and Anaplastic Lymphoma Kinase Rearrangements in Non-Small Cell Lung Carcinoma: A Tertiary Academic Institution Experience.

CONTEXT: Although epidermal growth factor receptor (EGFR)- and anaplastic lymphoma kinase (ALK)-directed therapies are not approved for patients with early-stage non-small cell lung carcinoma (NSCLC), many institutions perform EGFR and ALK testing for all patients with NSCLC at the time of initial diagnosis. Current consensus guidelines recommend EGFR testing and suggest ALK testing at the time of initial diagnosis for patients with advanced disease. OBJECTIVES: To examine the cost and clinical impact of EGFR and ALK testing of patients with early-stage NSCLC. DESIGN: Records from all patients with a diagnosis of NSCLC made on a nonresection specimen at our institution during a single calendar year (2012) were reviewed, and a cost analysis was performed. RESULTS: Of 133 total patients, 47 (35%) had early-stage (stage I or II) disease and 86 (65%) had locally advanced (stage III) or advanced (stage IV) disease at presentation. Eight of 47 patients with early-stage disease (17%) had progression/recurrence during 18 to 30 months of follow-up, 6 of 8 (75%) of whom had pathologic confirmation of progression/recurrence. The estimated additional cost of EGFR and ALK testing for all newly diagnosed patients with NSCLC at our institution is $75,200 per year, compared to testing only patients with locally advanced and advanced-stage disease. CONCLUSIONS: The cost of universal molecular testing of NSCLC is substantial. EGFR and ALK testing of patients with early-stage disease appears to have negligible clinical impact, as most patients do not have disease recurrence/progression. Those whose disease recurs/progresses typically undergo rebiopsy. Our findings do not support the practice of universal EGFR and ALK testing in NSCLC at the time of initial diagnosis.

A Population-Based Cost Analysis of Thoracoscopic Versus Open Lobectomy in Primary Lung Cancer.

BACKGROUND: Thoracoscopic lobectomy for primary lung cancer has become increasingly popular worldwide due to several advantages over open lobectomy including reduced pain, reduced length of hospital stay, and comparable oncologic outcomes. The costs of thoracoscopic versus conventional open lobectomy have been compared in several studies with variable results. We compared the costs of thoracoscopic versus open lobectomy in lung cancer patients in Taiwan. METHODS: Patients who underwent lobectomy for primary lung cancer from the Taiwan National Health Insurance Research Database (NHIRD) between 2004 and 2010 were identified. Patient characteristics, operative data, and costs for each part of the hospitalization for surgery and 30 days of care after discharge were analyzed. RESULTS: A total of 5366 patients with complete clinical data who underwent either conventional open lobectomy (n = 3166, 59 %) or thoracoscopic lobectomy (n = 2200, 41 %) for primary lung cancer were identified from the database. Compared with open lobectomy, thoracoscopic lobectomy was associated with younger age, less comorbidity, shorter anesthesia times, and reduced lengths of hospital stay. Total hospital costs, operative costs, and other costs were significantly higher in the thoracoscopic group. The 30-day after discharge costs were significantly lower in the thoracoscopic group. CONCLUSIONS: Thoracoscopic lobectomy for primary lung cancer in Taiwan was associated with higher total hospital costs but lower 30 days after discharge costs than open lobectomy. These differences may have resulted from higher operative and instrument costs in the thoracoscopic group.

Hospitalization costs of lung cancer diagnosis in Turkey: Is there a difference between histological types and stages?

INTRODUCTION: To establish the direct costs of diagnosing lung cancer in hospitalized patients. MATERIALS AND METHODS: Hospital data of patients who were hospitalized and diagnosed as lung cancer between September 2013 and August 2014 were retrospectively analyzed. Patients who underwent surgery for diagnosis and who were initiated with cancer treatment during the same hospital stay were excluded from study. Histological types and stages of lung cancer were determined. Expenses were grouped as laboratory costs, pathology costs, diagnostic imaging costs, overnight room charges, medication costs, blood center costs, consumable expenditures' costs and inpatient service charges (including consultants' service, electrocardiogram, follow-up, nursing services, diagnostic interventions). RESULT: Of the 68 patients, 55 (81%) had non-small cell lung cancer (NSCLC), 13 (19%) had small cell lung cancer (SCLC). 47% of patients with NSCLC had stage 4 disease and 86% of patients with SCLC had extensive stage disease. Median total cost per patient was 910 (95% CI= 832-1291) Euros (€). Of all costs, 37% were due to inpatient service charges and 22% were medication costs. Median total cost per patient was 912 (95% CI= 783-1213) € in NSCLC patients and 908 (95% CI= 456-2203) € in SCLC patients (p> 0.05). In NSCLC group, total cost per patient was 873 (95% CI= 591-1143) € in stage 1-2-3 diseases and 975 (95% CI= 847-1536) € in stage 4 disease (p> 0.05). In SCLC group total cost per patient was 937 € in limited stage and 502 (95% CI= 452-2508) € in extensive stage (p> 0.05). CONCLUSIONS: There is no significant difference between costs related to diagnosis of different lung cancer types and stages in patients hospitalized in a university hospital.

The role of receipt and timeliness of treatment in socioeconomic inequalities in lung cancer survival: population-based, data-linkage study.

BACKGROUND: Lung cancer survival is socioeconomically patterned, and socioeconomic inequalities in receipt of treatment have been demonstrated. In England, there are target waiting times for the referral (14 days) and treatment intervals (31 days from diagnosis, 62 days from GP referral). Socioeconomic inequalities in the time intervals from GP referral have been found. Cancer registry, Hospital Episode Statistics and lung cancer audit data were linked in order to investigate the contribution of these inequalities to socioeconomic inequalities in lung cancer survival. METHODS: Logistic regression was used to examine the likelihood of being alive 2 years after diagnosis, by socioeconomic position, for 22,967 lung cancer patients diagnosed in 2006-2009, and in a subset with stage recorded (n=5233). RESULTS: Socioeconomic inequalities in survival were found in a multivariable analysis adjusted for age, sex, histology, year, timely GP referral, performance status and comorbidity, with those in the most deprived socioeconomic group significantly less likely to be alive after 2 years (OR=0.77, 95% CI 0.66 to 0.88, p<0.001). When receipt of treatment was included in the analysis, the association no longer remained significant (OR=0.87, 95% CI 0.75 to 1.00, p=0.06). Addition of timeliness of treatment did not alter the conclusion. Patients treated within guideline targets had lower likelihood of two-year survival. CONCLUSIONS: Socioeconomic inequalities in survival from lung cancer were statistically explained by socioeconomic inequalities in receipt of treatment, but not by timeliness of referral and treatment. Further research is required to determine the currently unexplained socioeconomic variance in treatment rates.

Comparison of demographics, treatment patterns, health care utilization, and costs among elderly patients with extensive-stage small cell and metastatic non-small cell lung cancers.

BACKGROUND: Limited data exist regarding real-world treatment patterns, resource utilization, and costs of extensive-stage small cell lung cancer (esSCLC) among elderly patients in the United States. While abundant data are available on treatment patterns in metastatic non-small cell lung cancer (mNSCLC), to our knowledge no data exist comparing costs and resource use between patients with esSCLC or mNSCLC. METHODS: We retrospectively analyzed administrative claims data (2000-2008) of patients aged ≥65 years from the linked Surveillance, Epidemiology and End Results (SEER)-Medicare database. Patients were selected on the basis of having newly diagnosed esSCLC (n=5,855) or mNSCLC (n=24,090) during 1/1/2000-12/31/2005, and were required to have received cancer-directed therapy. Survival and other measures were compared between esSCLC and mNSCLC patients using Kaplan-Meier log-rank and univariate chi-square and t-tests. Study measures were followed from first diagnosis date of either esSCLC or mNSCLC until the earlier of death or end of the database. RESULTS: Survival between the cohorts did not differ significantly: mean of 10.4 months for esSCLC patients versus 11.1 months for mNSCLC; median survival was 7.4 months versus 5.9 months. A higher percentage of mNSCLC patients (vs. esSCLC) received radiation therapy (75.6% vs. 65.4%; P < 0.001) and surgery (13.6% vs. 7.8%; P < 0.001) during the metastatic disease period. Conversely, a higher percentage of esSCLC patients than mNSCLC patients received chemotherapy (85.5% vs. 60.3%; P < 0.001), red blood-cell transfusion (20.7% vs. 10.9%; P < 0.001), platelet transfusion (5.6% vs. 1.8%; P < 0.001), and growth-factor support (59.0% vs. 39.5%; P < 0.001). esSCLC patients incurred higher lifetime disease-related costs ($44,167 vs. $37,932; P < 0.001) and all-cause costs ($70,549 vs. $67,176; P < 0.001) than mNSCLC patients. CONCLUSIONS: Lifetime total and disease-related costs per patient were high. Increased use of chemotherapy, supportive care therapies (including growth factors), and disease-related hospitalizations were observed in esSCLC patients as compared with mNSCLC patients. Disease-related and all-cause costs for esSCLC also exceeded those of mNSCLC, except for hospice and skilled nursing services. Survival and per-patient costs for both groups underscore the unmet medical need for more effective therapies in patients with esSCLC or mNSCLC.

Estimating the lifelong health impact and financial burdens of different types of lung cancer.

BACKGROUND: Owing to the high mortality and rapidly growing costs related to lung cancer, it is worth examining the health benefits of prevention for major types of lung cancer. This study attempts to quantify the quality-adjusted life expectancy (QALE), loss-of-QALE, and lifetime healthcare expenditures of patients with different pathological types of lung cancer. METHODS: A national cohort consisting of 66,535 patients with pathologically verified lung cancer was followed for 13 years (1998-2010) to obtain the survival function, which was further extrapolated to lifetime. Between 2011 and 2012, EuroQol 5-dimension questionnaires were used to measure the quality of life (QoL) for 1,314 consecutive, cross-sectional samples. After multiplying the lifetime survival function by the utility values of QoL, we estimated the QALE and loss-of-QALE. We also collected the monthly healthcare expenditures, which included National Health Insurance-reimbursed and out-of-pocket direct medical costs, for 2,456 patients from 2005 to 2012. These values were multiplied by the corresponding survival probabilities to calculate lifetime healthcare expenditures after adjustments with medical care inflation rates and annual discount rates. RESULTS: The QALE for patients with small cell lung cancer, squamous cell carcinoma, and adenocarcinoma were 1.21, 2.37, and 3.03 quality-adjusted life year (QALY), with the corresponding loss-of-QALE of 13.69, 12.22, and 15.03 QALY, respectively. The lifetime healthcare expenditures were US$ 18,455 ± 1,137, 20,599 ± 1,787, and 36,771 ± 1,998, respectively. CONCLUSIONS: The lifelong health impact and financial burdens in Taiwan are heavier for adenocarcinoma than for squamous cell carcinoma. The cost-effectiveness of prevention programs could be directly compared with that of treatment strategies to improve patient value. And the methodology could be applied to other chronic diseases for resources planning of healthcare services.

Cisplatin plus etoposide versus other platin-based regimens for patients with extensive small-cell lung cancer: a systematic review and meta-analysis of randomised, controlled trials.

AIM: To determine whether the cisplatin plus etoposide (EP) combination was more efficacious and less toxic than other platinum-based regimens for patients with extensive-stage small-cell lung cancer. METHODS: We performed an extensive literature search (from their inception to July 2010). Two reviewers independently assessed search results and methodological quality of included studies. Pooled hazard ratios (HRs) and relative risks (RRs) were calculated according to a random-effects model. RESULTS: Twelve randomised, controlled trials involving seven different platinum-based chemotherapy regimens were included into this meta-analysis. The meta-analysis showed that compared with EP regimen, irinotecan plus cisplatin (IP) might decrease the risk of death (HR = 0.87, 95% confidence interval (CI) 0.78-0.97, P = 0.01) (five trials), unlike the sensitivity analysis (HR = 0.91, 95% CI 0.81-1.02, P = 0.12), progression-free survival (HR = 0.95, 95% CI 0.86-1.05, P = 0.28) and overall response rate (RR 1.08, 95% CI 0.93-1.24) that were not superior for IP. IP regimen produced more non-haematological toxicities and less haematological toxicities. One trial found that etoposide + cisplatin + epirubicin + cyclophosphamide and cisplatin + etoposide + ifosfamide regimen might prolong the overall survival respectively. Etoposide + cisplatin + epirubicin + cyclophosphamide regimen also might improve progression-free survival but with high rate of haematological toxicities. None of the other trials included in the study demonstrated a significant improvement in survival. CONCLUSIONS: There is no strong evidence that any clinical advantage for extensive small-cell lung carcinoma patients requiring chemotherapy when comparing EP with other platin-based regimens, with exception of IP that might prolong overall survival. The decision to prescribe which chemotherapy should take into consideration both cost and treatment preference.

The efficacy of PET staging for small-cell lung cancer: a systematic review and cost analysis in the Australian setting.

INTRODUCTION: This study aimed to establish from the published literature the efficacy of a positron emission tomography (PET)-based strategy for the staging of small-cell lung cancer compared to conventional methods, the potential impact on patient management and outcomes, and cost implications for the Australian health system. METHODS: EMBASE, Current Contents, PubMed, and OVID, databases were searched using relevant search terms. Reference lists of identified studies were examined for additional pertinent papers. Literature review identified 22 relevant studies containing data for 1663 patients. Studies were evaluated regarding the adequacy of pathological or clinical correlation of imaging findings. Efficacy of PET-staging was analyzed. The Medicare benefits schedule was used to compare costs of the two strategies. RESULTS: Published data confirm that PET staging has a sensitivity approaching 100% and specificity exceeding 90%. Data suggest that compared to conventional staging, PET can alter management (including radiotherapy portal changes) in at least 28% of patients, can result in the addition of life-prolonging radiotherapy in 6%, and avert unnecessary radiotherapy with associated toxicity in 9%. PET-based staging costs 1603 Australian dollars (AUD) and conventional staging 1610 AUD per patient. An additional 540,354 AUD may be saved annually through avoidance of unnecessary radiotherapy. CONCLUSIONS: PET-based staging seems superior to conventional staging, and can significantly alter patient management particularly with regard to the inclusion, omission, and portal design of radiotherapy. The initial costs of the two strategies do not seem significantly different. PET may ultimately reduce healthcare costs through avoidance of inappropriate thoracic radiotherapy. The major advantages of PET-staging may, however, lie in averting unnecessary toxicity and in the appropriate addition of thoracic radiotherapy with potential survival gains.

Epidemiology and treatment costs of bone metastases from lung cancer: a French prospective, observational, multicenter study (GFPC 0601).

INTRODUCTION: The aim of this prospective, observational, multicenter study was to examine the epidemiology and management costs of bone metastatic disease (BMD) in patients with lung cancer. METHODS: The analysis included all patients with BMD from lung cancer diagnosed between May 2006 and May 2007 in 40 centers. We analyzed their management and the direct costs of BMD from the health care provider's perspective, using a Markov model. Skeletal-related event (SRE) was defined as pathological fractures, spinal cord compression, or hypercalcemia (clinical SRE [cSRE]) for an initial analysis; a second analysis included palliative radiotherapy and surgery (therapeutic SRE [tSRE]). RESULTS: Among the 554 patients enrolled (62 ± 11 years, 76.5% males, 69.3% performance status 0/1, 91% non-small cell lung cancer), 24.7% had a cSRE and 26.7% a tSRE at baseline and 9% and 39% during follow-up, respectively; 81.8% received at least one chemotherapy cycle. The median survival time was 5.8 months, and the 1- and 2-year survival rates were 22% and 7%, respectively; there was no significant difference in overall survival between the patients with and without SRE at enrollment. The main BMD treatments were opiate therapy (77.7%), biphosphonates (52.3%), radiotherapy (42.1%), and surgery (9.2%). The mean monthly BMD treatment costs in euros were €190, €374, and €4672 for asymptomatic patients, symptomatic patients, and patients with SRE, respectively. The average first-year BMD management cost in euros was €3999 ± 4135 (95% confidence interval: 374-15,886), and 49.5% of this cost was attributable to patients with SRE. CONCLUSIONS: This analysis confirms the poor prognosis of BMD from lung cancer and underlines the burden of SRE in overall treatment costs.

Lung cancer treatment costs, including patient responsibility, by disease stage and treatment modality, 1992 to 2003.

OBJECTIVES: The objective of this analysis was to estimate costs for lung cancer care and evaluate trends in the share of treatment costs that are the responsibility of Medicare beneficiaries. METHODS: The Surveillance, Epidemiology, and End Results (SEER)-Medicare data from 1991-2003 for 60,231 patients with lung cancer were used to estimate monthly and patient-liability costs for clinical phases of lung cancer (prediagnosis, staging, initial, continuing, and terminal), stratified by treatment, stage, and non-small- versus small-cell lung cancer. Lung cancer-attributable costs were estimated by subtracting each patient's own prediagnosis costs. Costs were estimated as the sum of Medicare reimbursements (payments from Medicare to the service provider), co-insurance reimbursements, and patient-liability costs (deductibles and "co-payments" that are the patient's responsibility). Costs and patient-liability costs were fit with regression models to compare trends by calendar year, adjusting for age at diagnosis. RESULTS: The monthly treatment costs for a 72-year-old patient, diagnosed with lung cancer in 2000, in the first 6 months ranged from $2687 (no active treatment) to $9360 (chemo-radiotherapy); costs varied by stage at diagnosis and histologic type. Patient liability represented up to 21.6% of care costs and increased over the period 1992-2003 for most stage and treatment categories, even when care costs decreased or remained unchanged. The greatest monthly patient liability was incurred by chemo-radiotherapy patients, which ranged from $1617 to $2004 per month across cancer stages. CONCLUSIONS: Costs for lung cancer care are substantial, and Medicare is paying a smaller proportion of the total cost over time.

Topotecan for relapsed small cell lung cancer: a systematic review and economic evaluation.

BACKGROUND: Topotecan is a relatively new drug for use as a second-line treatment in patients with relapsed small cell lung cancer (SCLC). We performed a systematic review and economic evaluation of topotecan, and consider it here in relation to the NICE end of life criteria. METHODS: Seventeen bibliographic databases (including Cochrane library, Medline and Embase) were searched from 1990 to February 2009, and experts and manufacturers were consulted, to identify relevant randomised controlled trials (RCTs) which were selected according to prospectively defined criteria. An economic evaluation was undertaken to assess cost effectiveness compared with best supportive care (BSC) in the UK. RESULTS: Five RCTs were included. The clinical evidence indicates a statistically significant benefit of oral topotecan plus BSC compared to BSC alone for overall survival. Intravenous topotecan was similar in efficacy to both oral topotecan and CAV (cyclophosphamide, doxorubicin and vincristine). In the survival model, oral topotecan plus BSC was associated with an average gain in life expectancy of approximately 4 months, resulting in a gain of 0.183 quality-adjusted life years (QALYs). At an incremental cost of approximately £6200 the incremental cost effectiveness ratio (ICER) is £33,851 per QALY gained. CONCLUSIONS: Compared with BSC alone, oral topotecan for patients with relapsed SCLC was associated with improved health outcomes but at increased cost. The ICER is at the upper extreme of the range conventionally regarded as cost effective from an NHS decision making perspective. However, this treatment may fall under supplementary guidance for life extending, end of life treatments.

Stereotactic radiotherapy reduces treatment cost while improving overall survival and local control over standard fractionated radiation therapy for medically inoperable non-small-cell lung cancer.

PURPOSE: Radiation therapy (RT) is the standard alternative curative treatment option for medically inoperable early stage non-small-cell lung cancer (NSCLC). Recently, stereotactic body radiotherapy (SBRT) has shown substantial promise to improve local control rates as compared with conventional fractionated RT [external beam RT (EBRT)]. We compare treatment outcomes and costs between SBRT and EBRT in this patient population. MATERIALS AND METHODS: A total of 86 patients with Stage I (Tl-2 N0) NSCLC were treated with either EBRT (n=41) or SBRT (n=45) between January 2002 and April 2008. EBRT patients were treated to a median dose of 70 Gy with 3-dimensional conformal RT (n=39) or intensity-modulated radiation therapy (n=2). SBRT was delivered in 4 or 5 fractions to 48 (Tl, n=44) or 60 (T2, n=1) Gy. The actual cost was calculated using 2010 Medicare hospital-based Ambulatory Payment Classification and hospital-based physician fee screen reimbursement rates for both the technical and professional components. RESULTS: On the basis of a median number of fractions for this patient population, SBRT was significantly less expensive ($13,639 EBRT vs. $10,616 SBRT, P < 0.01). Survival analysis demonstrated superior 36-month overall survival using SBRT, 71% versus 42% for EBRT (P < 0.05). SBRT also reduced local failure by nearly 3 times compared with EBRT (12% vs. 34%, P=0.10). CONCLUSION: In this study of Stage I NSCLC patients, SBRT was found to be less expensive than standard fractionated EBRT, with the cost savings highly dependent on the number of SBRT fractions and EBRT technique (3-dimensional conformal RT vs. intensity-modulated radiation therapy). SBRT was also associated with superior local control and overall survival.

The clinical effectiveness and cost-effectiveness of topotecan for small cell lung cancer: a systematic review and economic evaluation.

OBJECTIVES: To assess the clinical effectiveness and cost-effectiveness of topotecan as second-line treatment for small cell lung cancer (SCLC). DATA SOURCES: Bibliographic databases were searched from 1990 to February 2009, including the Cochrane library, MEDLINE (Ovid), EMBASE (Ovid), PREMEDLINE In-Process & Other Non-Indexed Citations. Bibliographies of related papers were assessed and experts were contacted to identify additional references and the manufacturer's submission to NICE was also searched. REVIEW METHODS: Two reviewers independently screened titles and abstracts for eligibility. Inclusion criteria were applied to the full text of retrieved papers using a standard form. For the clinical effectiveness review, the studies were randomised controlled trials (RCTs), which included adult participants with relapsed SCLC who responded to first-line treatment and for whom re-treatment with first-line therapy was inappropriate. The treatment was topotecan (oral or intravenous, i.v.) compared with one another, best supportive care (BSC) or other chemotherapy regimens. Outcomes included measures of response or disease progression and measures of survival. For the cost-effectiveness review studies were eligible for inclusion if they reported cost-effectiveness, cost-utility, cost-benefit or cost-consequence analyses. Data extraction and quality assessment of included studies was undertaken by one reviewer and checked by a second. Studies were synthesised through a narrative review with full tabulation of results. An independent economic model estimated the cost-effectiveness of topotecan (oral or i.v.) compared with BSC. The model used survival analysis methods to derive estimates of mean survival for patients treated with topotecan or receiving BSC alone. These were combined with quality of life (QoL) weights to derive estimates of mean quality-adjusted life expectancy for patients receiving BSC alone or topotecan plus BSC. Categories of costs included in the model included drug use, chemotherapy administration and on-treatment monitoring, management of adverse events, monitoring for disease progression and palliative care. RESULTS: A total of 434 references were identified of which five were included in the clinical effectiveness review. In these trials topotecan was compared with BSC, CAV [cyclophosphamide, Adriamycin (doxorubicin) and vincristine] or amrubicin, or oral topotecan was compared with i.v. topotecan. No economic evaluations were identified. There were no statistically significant differences between groups when i.v. topotecan was compared with either CAV or oral topotecan for overall response rate (ORR). Response rate was significantly better in participants receiving i.v. amrubicin than in those receiving a low dose of i.v. topotecan (38% versus 13%, respectively, p = 0.039). There was a statistically significant benefit in favour of oral topotecan compared with BSC (HR 0.61, 95% CI 0.43 to 0.87, p = 0.01). Drug acquisition costs for four cycles of treatment were estimated at 2550 pounds for oral topotecan and 5979 pounds for i.v. topotecan. Non-drug treatment costs accounted for an additional 1097 pounds for oral topotecan and 4289 pounds for i.v. topotecan. Total costs for the modelled time horizon of 5 years were 4854 pounds for BSC, 11,048 pounds for oral topotecan and between 16,914 pounds and 17,369 pounds for i.v. topotecan (depending on assumptions regarding time progression). Life expectancy was 0.4735, 0.7984 and 0.7784 years for BSC, oral topotecan and i.v. topotecan respectively. Total quality-adjusted life-years (QALYs) were 0.2247 and 0.4077, for BSC and oral topotecan respectively, resulting in an incremental cost-effectiveness ratio (ICER) of 33,851 pounds per QALY gained. Total QALYs for i.v. topotecan were between 0.3875 and 0.4157 (depending on assumptions regarding time progression) resulting in an ICER between 74,074 pounds and 65,507 pounds per QALY gained. CONCLUSIONS: Topotecan appeared to be better than BSC alone in terms of improved survival, and was as effective as CAV and less favourable than i.v. amrubicin in terms of response. Oral topotecan and i.v. topotecan were similar in efficacy. Topotecan offers additional benefit over BSC, but at increased cost. ICERs for i.v. topotecan, compared with BSC, were high and suggest that it is unlikely to be a cost-effective option. The ICER for oral topotecan is at the upper extreme of the range conventionally regarded as cost-effective from an NHS decision-making perspective. Further research into the QoL of patients with relapsed SCLC could identify the impacts of disease progression and treatment response.