Treatment characteristics and outcomes in lower-risk, non-del(5q) myelodysplastic syndromes: findings from a medical record review in the USA, Canada and Europe.

Aim: To assess treatment patterns and outcomes in patients with non-del(5q) lower-risk myelodysplastic syndromes.Methods: Patient medical records were reviewed in the USA, Canada (CAN), UK and the EU.Results: Analysis included 119 patients in the USA/CAN (median age, 61.5 years) and 245 patients in the UK/EU (median age, 67.3 years). Most patients received erythropoiesis-stimulating agents (ESAs) as first-line (1L) therapy (USA/CAN: 89.0%; UK/EU: 90.2%). A substantial proportion of 1L erythropoiesis-stimulating agent-treated patients were transfusion dependent before 1L (USA/CAN: 37.1%; UK/EU: 51.2%); a small percentage of these patients achieved transfusion independence during 1L therapy (USA/CAN: 2.8%; UK/EU: 14.4%).Conclusion: These findings highlight an unmet need for more effective treatments among patients with non-del(5q) lower-risk myelodysplastic syndromes.

[Box: see text].

Treatment Patterns and Persistent Disease Activity in Patients With Eosinophilic Esophagitis: A Retrospective Cohort Study.

Background and Aims: Limited real-world nontertiary care evidence on the patient therapeutic journey and disease burden of eosinophilic esophagitis (EoE) exists. The aim was to collect real-world data on the EoE patient journey across different age groups. Methods: This retrospective, real-world, cohort study used electronic medical records and claims data provided by a rural integrated US healthcare system. Eligibility criteria included ≥ 2 diagnoses of EoE (2009-2018), ≥ 1 endoscopy, and ≥ 12 months of data before and after the index date (the first endoscopy date during the 180 days before and the 365 days after the first EoE diagnosis). Clinical findings, all-cause healthcare resource utilization, specialists consulted, therapies, and markers of disease progression were analyzed. Results: Overall, 613 patients were enrolled: 0-11 (children, n = 182), 12-17 (adolescents, n = 146), 18-54 (adults, n = 244), and ≥ 55 years old (older adults, n = 41). Post index, the prevalence of signs and symptoms increased. At baseline, most endoscopies were abnormal (80.5%) and most peak eosinophil counts were > 15 eosinophils/high-power field (87.9%); post index, all age groups had endoscopic and histologic improvements. However, 3 years post index, abnormal endoscopic appearance (62.3%) and histologic activity (51.2%) were observed. Patients of all ages exhibited considerable all-cause healthcare resource utilization. During follow-up, 86.3% of patients consulted a specialist. Before and after index, proton pump inhibitors and corticosteroids were the most commonly used pharmacological therapies; 44.0% of patients discontinued their first treatment post index. Disease progression occurred in 13.9% of patients post index. Conclusion: In this setting, patients with EoE irrespective of age face difficult therapeutic journeys with substantial disease burden.

Clinical characteristics, treatment patterns, and outcomes in adult patients with germline BRCA1/2-mutated, HER2-negative advanced breast cancer: a retrospective medical record review in the United States.

Aim: To examine clinical characteristics, real-world treatment patterns, and health outcomes among patients with germline BRCA1/2-mutated, human epidermal growth factor receptor 2 (HER2)-negative advanced breast cancer (ABC). Methods: A retrospective analysis was conducted using medical records from patients with HER2-negative ABC with BRCA1/2 mutation who received cytotoxic chemotherapy. Data were stratified into groups with triple-negative breast cancer (TNBC) or hormone receptor-positive (HR+)/HER2-negative diagnoses. Time-to-event outcomes (i.e., real-world progression-free survival [rwPFS] and overall survival [OS]) were calculated to summarize health outcomes. Results: When diagnosed with ABC, most patients were younger than 60 years (mean age = 57.3 years), were white (76.4%), and had a family history of BRCA-related cancer (71.5%). A total of 305 patient records were examined; 194 patients (63.6%) had advanced TNBC, and 111 patients (36.4%) had HR+/HER2-negative ABC. Chemotherapy was primarily used as first-line treatment for both subgroups, but the TNBC subgroup received poly (ADP-ribose) polymerase (PARP) inhibitors at triple the rate as a second-line treatment and double the rate as a third-line treatment compared with the HR+/HER2-negative subgroup. Two-year OS rates were similar between the TNBC (73.9%) and the HR+/HER2-negative subgroups (77.0%), and anemia, nausea, and neutropenia were the most commonly reported toxicities across all treatments. Conclusion: Clinicians should consider the use of targeted agents such as PARP inhibitors in earlier lines of therapy for ABC given the growing evidence that PARP inhibitors may improve PFS compared with chemotherapy while potentially offering a more manageable toxicity profile and improved quality of life.

Biomarker testing in patients diagnosed with advanced/metastatic medullary thyroid cancer in the USA.

Aim: To describe real-world testing patterns for RET in US patients with advanced/metastatic medullary thyroid cancer and determine consistency of real-world testing practices with national guidelines. Materials & methods: The authors performed a retrospective medical record analysis of patients with advanced/metastatic medullary thyroid cancer who initiated systemic therapy between 2013 and 2018. Seventy-five US-based oncologists collected the data using a customized electronic data collection form. Results: A total of 59.6% (121 of 203) of patients underwent testing for RET, and 37.2% (45 of 121) had a RET mutation, of which 55.6% were identified as RET mutation-positive before initial diagnosis. Overall, 90 (44.3%) patients were tested for biomarkers on or after initial diagnosis, with RET being the most tested (95.6%) biomarker. Conclusion: The authors' findings suggest an opportunity to improve testing rates in accordance with treatment guidelines.

Mutations in the RET gene are common in patients with medullary thyroid cancer (MTC). As RET mutations are involved in the development of MTC, several treatment guidelines recommend counseling patients and testing for mutations in the RET gene in all patients with MTC. However, limited data are available on RET testing patterns in the USA in this patient population. In this study, the authors determined testing patterns for RET in patients with advanced or metastatic MTC in the USA using real-world data and found that only 60% of patients were tested for RET (i.e., testing for presence of RET mutations was observed in less than two-thirds of all patients included in the study). These results demonstrate the need for improved testing for RET mutations in patients with MTC in alignment with the treatment guidelines in routine clinical practice in the USA.

Real-world clinical outcomes of patients with myelofibrosis treated with ruxolitinib: a medical record review.

Aim: To assess real-world ruxolitinib treatment patterns and outcomes in patients diagnosed with primary or secondary myelofibrosis. Materials & methods: Patient medical records were reviewed in six countries. Results: Eligible patients (n = 469) had a mean age of 63.5 years, and most were male (66.5%) with primary myelofibrosis (78.5%). Median duration of ruxolitinib treatment was 13.1 months; 40% of patients initiated treatment at the recommended dose. The Kaplan-Meier estimate of median survival from ruxolitinib initiation was 44.4 months (95% CI, 38.8-50.2 months). Approximately one quarter (23%) of patients continued ruxolitinib after progression. Conclusion: These results suggest an unmet need for more effective treatments for patients with myelofibrosis who failed ruxolitinib.

Treatment practices and costs among patients with psoriatic arthritis: A Japanese hospital claims database analysis.

OBJECTIVE: Assess patient characteristics, real-world treatment patterns, and health care resource utilization (HCRU) among patients with psoriatic arthritis (PsA) in Japan. METHODS: Patients diagnosed with PsA from April 2009 through July 2017 were identified from the Medical Data Vision database. Patient characteristics, treatment patterns, and HCRU were evaluated for these patients. RESULTS: A total of 639 patients met inclusion criteria and were included in the analysis for patients with a PsA diagnosis. Over 12 months following diagnosis, patients received oral NSAIDs (61.7%), conventional synthetic disease-modifying antirheumatic drugs (DMARDs) (55.1%), corticosteroids (35.1%), topical NSAIDs (34.0%), adalimumab (14.7%), infliximab (9.7%), secukinumab (5.0%), ustekinumab (4.5%), ixekizumab (1.6%), and golimumab (1.6%). A total of 227 (35.5%) patients initiated biologic DMARDs (bDMARDs) over the median 25.2 months of study follow-up. Compared with the overall group of patients diagnosed with PsA, patients who initiated bDMARDs had higher median total per-patient health care costs ($27,772 vs. $11,316), lower median per-patient hospitalization costs ($31,164 vs. $39,359), and fewer median hospital days per admission (8.0 vs. 12.0 days). CONCLUSION: This study presents knowledge of the current state of patient characteristics, treatment patterns, HCRU, and costs among patients with PsA in Japan. Considering the relatively recent guideline recommendations, the preliminary treatment patterns suggest physicians may be following treatment guidelines.

Treatment patterns, adverse events, and direct and indirect economic burden in a privately insured population of patients with HR+/HER2- metastatic breast cancer in the United States.

BACKGROUND: Real-world evidence specific to HR+/HER2- metastatic breast cancer (MBC) prior to introduction of CDK4/6 inhibitors is limited. In an effort to provide context for the introduction of new treatments, we assessed treatment patterns, adverse events, productivity loss, and direct/indirect economic burden in a privately insured population of patients with HR+/HER2- MBC. RESEARCH DESIGN AND METHODS: Using a retrospective cohort design, patients aged 18-64 years, selected from MarketScan databases (2007-2014), were analyzed using descriptive and multivariable methods. RESULTS: Among 5,563 eligible patients, endocrine therapy was the most common first-line (1L) therapy; its utilization trended downward from 63% (1L) to 23% (4L), with a simultaneous increase in chemotherapy use, 25% (1L) to 50% (4L). Two hundred and seventy-eight unique treatment regimens were used in the 1L setting. The average per patient monthly all-cause costs were $14,424. The 12-month indirect costs for short-term disability were substantially higher in MBC patients ($10,397) than in matched noncancer patients ($394). CONCLUSION: The increasing use of chemotherapy as patients progressed to second and later lines and the substantial direct/indirect economic burden underscore an unmet need. The high number of 1L regimens highlights significant heterogeneity and a lack of consensus related to the management of HR+/HER2- MBC in routine practice.

Treatment patterns and health care resource utilization among Japanese patients with ankylosing spondylitis: A hospital claims database analysis.

OBJECTIVES: To understand the current state of treatment patterns and health care resource utilization among patients in Japan with ankylosing spondylitis (AS) managed in the real-world setting. METHODS: Patient records from the Medical Data Vision database were analyzed to identify patients with ICD-10 AS from April 2009 through July 2017. Measures evaluated included demographic, clinical, and other characteristics at diagnosis; treatment patterns; health care resource utilization; and costs. RESULTS: Four hundred and seventeen patients met the study's inclusion criteria. Treatments observed during the first year after the initial AS diagnosis included nonsteroidal anti-inflammatory drugs (79.6%), corticosteroids (39.3%), methotrexate (22.3%), sulfasalazine (16.8%), adalimumab (14.2%), and infliximab (12.2%). At any time during the mean 33 months of study follow-up, biologic disease-modifying antirheumatic drugs (bDMARDs) were initiated by 115 patients. During the study follow-up, patients who initiated bDMARDs had higher median total per-patient annual health care costs ($26,937 vs $15,323), lower median per-patient hospitalization costs ($29,817 vs. $39,509), and fewer median hospital days per admission (7.0 vs. 11.0 days) compared with the overall group of patients diagnosed with AS. CONCLUSION: This database study provides knowledge of patient characteristics, treatment patterns, HCRU, and costs for patients with AS in Japan. The study outcomes demonstrate a need for increased awareness of proper AS management.

Treatment patterns and survival among older adults in the United States with advanced soft-tissue sarcomas.

BACKGROUND: To describe patient and tumor characteristics, treatments, and survival among older adults in the United States with advanced soft-tissue sarcoma (STS), across and by categories of specifically defined histologic subtypes. METHODS: We conducted a retrospective cohort analysis using the SEER. The study population comprised patients ≥ 65 years old with advanced STS (excluding osteosarcoma, Kaposi sarcoma, and gastrointestinal stromal tumors) diagnosed from January 1, 2001 to December 31, 2011. RESULTS: Of 4274 study patients, 2103 (49.2%) were male. Mean age was 77.8 years, and 1539 (36.0%) had distant disease at initial diagnosis. The most common histologic categories were leiomyosarcoma (922[21.6%]), undifferentiated pleomorphic sarcoma (652[15.3%]), and liposarcoma (554[13.0%]). Overall, 1227 (28.7%) patients received first-line systemic therapy. Among these patients, 325 (26.5%) received docetaxel plus gemcitabine and 231 (18.8%) received doxorubicin alone. Only 476 patients received second-line therapy (11.1%), most commonly doxorubicin alone (n = 101). Median overall survival (95% confidence interval) from advanced STS diagnosis was 8.9 (8.3, 9.7) months. CONCLUSIONS: Although previous studies of younger populations reported anthracycline-based therapy predominated in first line, our study of older advanced STS patients found that docetaxel plus gemcitabine was most commonly used. Despite variation by histologic category, prognosis remains poor for older adult patients with advanced STS.

Chronologic Age at Hospitalization for Respiratory Syncytial Virus Among Preterm and Term Infants in the United States.

INTRODUCTION: Respiratory syncytial virus (RSV) is the leading cause of hospitalization among infants in the United States, and the risk for RSV hospitalizations is greater for infants born preterm. Recent studies in preterm and term infants have shown that RSV hospitalization rates vary considerably depending on infant chronologic age. This study sought to aggregate the data available from published literature and from nationally representative databases of US infant hospitalizations to generate a composite description of the effect of young chronologic age on RSV hospitalizations among US preterm and term infants by individual month of age. METHODS: Data describing the relative incidence of RSV hospitalizations by individual month of chronologic age during the first year of life were obtained from recently published studies, the 2006-2011 National Inpatient Sample databases, and the 2006 and 2009 Kids Inpatient Databases. RESULTS: All data sources showed that ≥20% of infant RSV hospitalizations occurred in the second month of life and >50% and >75% of RSV hospitalizations were observed during the first 3 and 6 months of life, respectively. These findings were consistent for both preterm and term infants. CONCLUSION: Data from multiple sources demonstrate that the greatest risk of RSV hospitalization occurs during the first 6 months of life among US preterm and term infants. Strategies to prevent infant RSV hospitalizations should be targeted to infants during the first months of life. FUNDING: AstraZeneca.

Cost-Effectiveness of Treatment Sequences of Chemotherapies and Targeted Biologics for Elderly Metastatic Colorectal Cancer Patients.

BACKGROUND: Treatment patterns for metastatic colorectal cancer (mCRC) patients have changed considerably over the last decade with the introduction of new chemotherapies and targeted biologics. These treatments are often administered in various sequences with limited evidence regarding their cost-effectiveness. OBJECTIVE: To conduct a pharmacoeconomic evaluation of commonly administered treatment sequences among elderly mCRC patients. METHODS: A probabilistic discrete event simulation model assuming Weibull distribution was developed to evaluate the cost-effectiveness of the following common treatment sequences: (a) first-line oxaliplatin/irinotecan followed by second-line oxaliplatin/irinotecan + bevacizumab (OI-OIB); (b) first-line oxaliplatin/irinotecan + bevacizumab followed by second-line oxaliplatin/irinotecan + bevacizumab (OIB-OIB); (c) OI-OIB followed by a third-line targeted biologic (OI-OIB-TB); and (d) OIB-OIB followed by a third-line targeted biologic (OIB-OIB-TB). Input parameters for the model were primarily obtained from the Surveillance, Epidemiology, and End Results-Medicare linked dataset for incident mCRC patients aged 65 years and older diagnosed from January 2004 through December 2009. A probabilistic sensitivity analysis was performed to account for parameter uncertainty. Costs (2014 U.S. dollars) and effectiveness were discounted at an annual rate of 3%. RESULTS: In the base case analyses, at the willingness-to-pay (WTP) threshold of $100,000/quality-adjusted life-year (QALY) gained, the treatment sequence OIB-OIB (vs. OI-OIB) was not cost-effective with an incremental cost-effectiveness ratio (ICER) per patient of $119,007/QALY; OI-OIB-TB (vs. OIB-OIB) was dominated; and OIB-OIB-TB (vs. OIB-OIB) was not cost-effective with an ICER of $405,857/QALY. Results similar to the base case analysis were obtained assuming log-normal distribution. Cost-effectiveness acceptability curves derived from a probabilistic sensitivity analysis showed that at a WTP of $100,000/QALY gained, sequence OI-OIB was 34% cost-effective, followed by OIB-OIB (31%), OI-OIB-TB (20%), and OIB-OIB-TB (15%). CONCLUSIONS: Overall, survival increases marginally with the addition of targeted biologics, such as bevacizumab, at first line and third line at substantial costs. Treatment sequences with bevacizumab at first line and targeted biologics at third line may not be cost-effective at the commonly used threshold of $100,000/QALY gained, but a marginal decrease in the cost of bevacizumab may make treatment sequences with first-line bevacizumab cost-effective. Future economic evaluations should validate the study results using parameters from ongoing clinical trials. DISCLOSURES: This study was supported in part by a grant from the Agency for Healthcare Research and Quality (R01-HS018956) and in part by a grant from the Cancer Prevention and Research Institute of Texas (RP130051), which were obtained by Du. The authors report no conflicts of interest. Study concept and design were primarily contributed by Parikh, along with the other authors. All authors participated in data collection, and Parikh took the lead in data interpretation and analysis, along with Lairson and Morgan, with assistance from Du. The manuscript was written primarily by Parikh, along with Lairson, Morgan, and Du, and revised by Parikh.

Patterns of Treatment Sequences in Chemotherapy and Targeted Biologics for Metastatic Colorectal Cancer: Findings from a Large Community-Based Cohort of Elderly Patients.

BACKGROUND: Over the last decade, multiple chemotherapies/targeted biologics have been approved for metastatic colorectal cancer (mCRC). However, evidence is limited with regards to the array of treatments received by mCRC patients. OBJECTIVE: This study examines treatment sequences (first- to third-line chemotherapy/targeted biologics) and the factors associated with first-line targeted biologics and common treatment sequences for elderly mCRC patients treated in a community setting. METHODS: A retrospective cohort study was conducted in mCRC patients diagnosed from January 2004 through December 2009 using the Surveillance, Epidemiology and End Results Medicare-linked database. The treatment sequences administered to elderly mCRC patients were empirically identified. RESULTS: Of 4418 mCRC patients who received treatment, 1370 (31 %) received first, second, and third line; 1164 (26 %) received first and second line; and 1884 (43 %) received only first line. The most common first line of treatment for mCRC patients was 5-fluorouracil/leucovorin + oxaliplatin (FOLFOX) + bevacizumab (23 %) and FOLFOX (23 %). 5-fluorouracil/leucovorin + irinotecan (FOLFIRI)-based regimens were commonly (22 %) administered in second line. The most common treatment sequence was first-line oxaliplatin or irinotecan followed by second-line oxaliplatin or irinotecan + bevacizumab followed by a third-line targeted biologic. Of patients who received first-line therapy, 47 % also received a targeted biologic, and the factors associated were age, comorbidity score, cancer site, geographic location, and year of diagnosis. CONCLUSION: Elderly mCRC patients receive a multitude of treatments in various sequences. Further exploration of the comparative effectiveness of treatment sequences may yield important information for improving mCRC survival.

Cost-Effectiveness of Chemotherapy for Breast Cancer and Age Effect in Older Women.

BACKGROUND: Previous economic evaluations compared specific chemotherapy agents using input parameters from clinical trials and resource utilization costs. Cost-effectiveness of treatment groups (drug classes) using community-level effectiveness and cost data, however, has not been assessed for elderly patients with breast cancer. OBJECTIVE: To assess the cost-effectiveness of chemotherapy regimens by age and disease stage under "real-world" conditions for patients with breast cancer. METHODS: The Surveillance Epidemiology and End Results-Medicare data were used to identify patients with breast cancer with American Joint Committee on Cancer stage I/II/IIIa, hormone receptor-negative (estrogen receptor-negative and progesterone receptor-negative) patients from 1992 to 2009. Patients were categorized into three adjuvant treatment groups: 1) no chemotherapy, 2) anthracycline, and 3) non-anthracycline-based chemotherapy. Median life-years and quality-adjusted life-years (QALYs) were measured using Kaplan-Meier analysis and were evaluated against average total health care costs (2013 US dollars). RESULTS: A total of 4575 patients (propensity score-matched) were included for the primary analysis. The anthracycline group experienced 12.05 QALYs and mean total health care costs of $119,055, resulting in an incremental cost-effectiveness ratio of $7,688 per QALY gained as compared with the no chemotherapy group (QALYs 7.81; average health care cost $86,383). The non-anthracycline-based group was dominated by the anthracycline group with lower QALYs (9.56) and higher health care costs ($122,791). Base-case results were found to be consistent with the best-case and worst-case scenarios for utility assignments. Incremental cost-effectiveness ratios varied by age group (range $3,790-$90,405 per QALY gained). CONCLUSIONS: Anthracycline-based chemotherapy was found cost-effective for elderly patients with early stage (stage I, II, IIIa) breast cancer considering the US threshold of $100,000 per QALY. Further research may be needed to characterize differential effects across age groups.

Racial and geographic disparities in the patterns of care and costs at the end of life for patients with lung cancer in 2007-2010 after the 2006 introduction of bevacizumab.

OBJECTIVES: To examine racial/ethnic and geographical disparities in cancer care and costs during the last 6 months of life for lung cancer decedents after the Food and Drug Administration's approval of expensive bevacizumab in October 2006. METHODS: We identified 37,393 cases from the Surveillance, Epidemiology and End Results (SEER) cancer registries and Medicare linked databases who were diagnosed with non-small cell lung cancer of all stages in 1991-2009 and died between July 2007 and December 2010. RESULTS: Overall, the proportion of patients receiving chemotherapy/targeted therapy (31.0%), bevacizumab (4.6%), growth factors (16.0%), surgery (2.8%), and hospice care (60.9) in the last 6 months of life was higher in whites than in other ethnic populations. Hospitalization rate was higher in blacks (83.2%) than in whites (76.0%) and others (78.0%). Those from metro areas had slightly higher percentages of receiving chemotherapy/targeted therapy, bevacizumab, growth factors, and hospice care, but had a higher hospitalization rate and lower emergency care visit. Mean total health care cost was $42,749 for the last 6 months of life in patients with lung cancer. Adjusted mean health care cost in the last 6 months of life was significantly higher in blacks or other ethnic population as compared to whites. CONCLUSION: There were substantial racial/ethnic and geographic disparities in the types of cancer care and costs in the last 6 months of life among lung cancer decedents, regardless of the length of survival times and hospice care status. A clinical guideline may help the appropriate use of costly treatment modalities and minimize racial/geographic disparities.

Comparative Effectiveness of Chemotherapy Regimens in Prolonging Survival for Two Large Population-Based Cohorts of Elderly Adults with Breast and Colon Cancer in 1992-2009.

OBJECTIVES: To compare the effectiveness of chemotherapy in prolonging survival according to age in breast and colon cancer. DESIGN: Retrospective cohort study with a matched cohort analysis based on the conditional probability of receiving chemotherapy. SETTING: The 16 Surveillance, Epidemiology, and End Results (SEER) areas from the SEER-Medicare linked database. PARTICIPANTS: Women diagnosed with Stage I to IIIa hormone receptor-negative breast cancer (n = 14,440) and 26,893 men and women with Stage III colon cancer (n = 26,893) aged 65 and older in 1992 to 2009. MEASUREMENTS: The main exposure was the receipt of chemotherapy, and the main outcome was mortality. RESULTS: In women with breast cancer aged 65 to 69, the risk of all-cause mortality was statistically significantly lower in those who received chemotherapy than in those who did not in the entire cohort (hazard ratio (HR) = 0.70, 95% confidence interval (CI) = 0.57-0.88) and in a propensity-matched cohort (HR = 0.82, 95% CI = 0.70-0.96) after adjusting for measured confounders. These patterns were similar in participants aged 70 to 74 and 75 to 79, but in women aged 80 to 84 and 85 to 89, risk of all-cause mortality was no longer significantly lower in those receiving chemotherapy in the entire and matched cohorts, except that, in a small number of women who received doxorubicin (Adriamycin) and cyclophosphamide (Cytoxan), risk of mortality was significantly lower for those aged 80 to 84. Chemotherapy appeared to be effective in all ages from 65 through 84 in participants with Stage III colon cancer. For example, in those aged 85 to 89, chemotherapy was significantly associated with lower risk of mortality in the entire cohort (HR = 0.79, 95% CI = 0.67-0.92) and the matched cohort (HR = 0.79, 95% CI = 0.66-0.95). CONCLUSION: The effectiveness of chemotherapy decreased with age in participants with breast cancer, in whom chemotherapy appears to be effective until age 79 except for the doxorubicin-cyclophosphamide combination, which was effective in participants aged 80 to 84. In individuals with Stage III colon cancer, chemotherapy appears to be effective to age 89. These findings were consistent with those of randomized clinical trials.

Cost Effectiveness of Chemotherapeutic Agents and Targeted Biologics in Ovarian Cancer: A Systematic Review.

BACKGROUND: Adjuvant chemotherapy is a key component of advanced ovarian cancer treatment, when surgery alone is not sufficient. Recurrence is common in ovarian cancer patients and most women require prolonged second-line and higher-line chemotherapy. With newer targeted therapies, modest improvements in survival and quality of life may be attained at substantial cost, but the relative economic efficiency of these newer agents remains unknown. OBJECTIVE: We undertook this systematic review to comprehensively evaluate the cost-effectiveness of various chemotherapeutic and targeted therapy alternatives for ovarian cancer. METHODS: We searched Medline, PubMed, and Embase databases to identify economic evaluations published over the last 18 years (1996-2014). From the 2513 unique papers retrieved, 74 full texts were selected for full-text review based on a priori eligibility criteria. Two authors independently reviewed these articles to determine eligibility for final review. The quality of the included studies was assessed using the Quality of Health Economic Studies (QHES). RESULTS: A total of 28 studies were included for reporting. Administration of intravenous cisplatin-paclitaxel combination chemotherapy for first-line treatment was the most cost-effective alternative (2014 US dollars [USD] equivalent incremental cost-effectiveness ratio [ICER] ~US$17,000-US$27,000 per life year gained [LYG]), while the use of bevacizumab did not demonstrate similar value for money (2014 USD equivalent ICER was greater than US$200,000 per quality-adjusted life-year [QALY]). For second-line treatment, the use of platinum-paclitaxel combination or platinum monotherapy was cost-effective compared with platinum monotherapy or best supportive care, respectively, in women with recurrent platinum-sensitive disease. For patients with partial platinum sensitivity, pegylated liposomal doxorubicin (PLD) plus trabectedin may be cost-effective (2014 USD equivalent ICER was ~US$57,000-US$62,000 per QALY) compared with PLD alone. For recurrent platinum-resistant cases, there was limited evidence to conclude the most valuable treatment; though one study showed that best supportive care was most cost-effective, while second-line monotherapy with doxorubicin (2014 USD equivalent ICER was ~US$90,000 per LYG) may also be cost-effective compared with best supportive care. CONCLUSIONS: Despite varying methodological approaches and multiple sources for cost and effectiveness inputs, this systematic review demonstrated that standard platinum-taxane combination chemotherapy for first-line treatment was most cost-effective. There was unanimous agreement that bevacizumab was not a cost-effective front-line therapy compared with platinum-taxane combination for the overall ovarian cancer population, though its use in the high-use population may yield better value. For second-line treatment, platinum-based chemotherapy remained cost-effective among patients with recurrent platinum-sensitive disease, while there was limited evidence to conclude the most valuable treatment alternative among patients with recurrent platinum-resistant disease. Future research incorporating real-world data is essential to corroborate findings from trial-based economic evaluations. In addition, for improving consistency in reporting and quality of studies, incorporating QALYs in this population is important, especially since chemotherapy is administered for lengthy periods of time.

Cost-utility analysis of chemotherapy regimens in elderly patients with stage III colon cancer.

BACKGROUND: Chemotherapy prolongs survival for stage III colon cancer patients but community-level evidence on the effectiveness and cost effectiveness of treatment for elderly patients is limited. Comparisons were between patients receiving no chemotherapy, 5-fluorouracil (5-FU), and FOLFOX (5-FU + oxaliplatin). METHODS: A retrospective cohort study was conducted using the Surveillance Epidemiology, and End Results (SEER)-Medicare linked database. Patients (≥65 years) with American Joint Committee on Cancer stage III colon cancer at diagnosis in 2004-2009 were identified. The 3-way propensity score matched sample included 3,534 patients. Effectiveness was measured in life-years and quality-adjusted life-years (QALYs). Medicare costs (2010 US dollars) were estimated from diagnosis until death or end of study. RESULTS: FOLFOX patients experienced 6.06 median life-years and 4.73 QALYs. Patients on 5-FU had 5.75 median life-years and 4.50 median QALYs, compared to 3.42 and 2.51, respectively, for the no chemotherapy patients. Average total healthcare costs ranged from US$85,422 for no chemotherapy to US$168,628 for FOLFOX. Incremental cost-effectiveness ratios (ICER) for 5-FU versus no chemotherapy were US$17,131 per life-year gained and US$20,058 per QALY gained. ICERs for FOLFOX versus 5-FU were US$139,646 per life-year gained and US$188,218 per QALY gained. Results appear to be sensitive to age, suggesting that FOLFOX performs better for patients 65-69 and 80+ years old while 5-FU appears most effective and cost effective for the age groups 70-74 and 75-79 years. CONCLUSION: FOLFOX appears more effective and cost effective than other strategies for colon cancer treatment of older patients. Results were sensitive to age, with ICERs exhibiting a U-shaped pattern.

Cost-utility analysis of platinum-based chemotherapy versus taxane and other regimens for ovarian cancer.

OBJECTIVES: Most economic evaluations of chemotherapies for ovarian cancer patients have used hypothetical cohorts or randomized control trials, but evidence integrating real-world survival, cost, and utility data is limited. METHODS: A propensity score-matched cohort of 6856 elderly (≥65 years) ovarian cancer patients diagnosed from 1991 to 2005 from the Surveillance, Epidemiology, and End Results-Medicare data cohort were included. Treatment regimens (i.e., no chemotherapy, platinum-based only, platinum plus taxane, and other nonplatinum) were identified in the 6 months postdiagnosis. Patients were followed until death or end of study (December 2006). Effectiveness was measured in quality-adjusted life-years (QALYs), and total health care costs were measured by using a payer's perspective (2009 US dollars). Methodological and statistical uncertainties were accounted by including alternative scenarios (for utility values) and net monetary benefit approach. Incremental cost-effectiveness ratios (ICERs) were calculated, and stratified analyses were performed by tumor stages and age groups. RESULTS: On comparing the platinum-based group versus no chemotherapy, we found that the ICER was $30,073/QALY and $58,151/QALY for early- and late-stage disease, respectively, while other nonplatinum and platinum plus taxane groups were dominated (less effective and more costly). Similar results were found across alternative scenarios and age groups. For patients 85 years or older, platinum plus taxane, however, was not dominated by the platinum-based group, with an ICER of $133,892/QALY. CONCLUSIONS: Following elderly ovarian cancer patients over a lifetime using real-world longitudinal data and adjusting for quality of life, we found that treatment with platinum-based regimen was the most cost-effective treatment alternative.

Comparative effectiveness of platinum-based chemotherapy versus taxane and other regimens for ovarian cancer.

The aim was to compare the two most commonly recommended chemotherapy regimens (platinum-based chemotherapy and platinum-taxane combination) with non-platinum-based chemotherapy and those with no chemotherapy in a large nationwide and population-based cohort of patients with ovarian cancer with up to 17 years of follow-up. We studied 12,181 patients diagnosed with stages I-IV ovarian cancer at age ≥ 65 in 1991-2005 from the 16 areas of the United States. We also performed matched cohort analyses based on conditional probability of receiving platinum chemotherapy in 3,428 patients. In patients with early stage ovarian cancer, those who received platinum-taxane combination had the highest 5-year all-cause (62.5 %) and cancer-specific (65.1 %) survival rates, as compared to 51.5 and 63.7 % in those without chemotherapy. After adjusting for potential confounders, hazard ratios of all-cause mortality (0.66, 95 % CI 0.55-0.79) and cancer-specific mortality (0.74, 0.61-0.90) were significantly lower in patients receiving platinum-taxane combination as compared to those without chemotherapy. Among patients with late-stage ovarian cancer, risks of mortality were significantly reduced in patients who received both platinum and taxane (0.38, 0.36-0.41 for all-cause mortality; 0.40, 0.37-0.42 for cancer-specific mortality). Dose-response relationship appeared strong within each of the three chemotherapy regimens. These results and trends were almost identical in the matched cohort. Platinum-taxane combination chemotherapy and platinum-based chemotherapy without taxane were effective in prolonging survival with a significant dose-response relationship among patients with late-stage ovarian cancer. Among those with early stage tumors, platinum-taxane combination appeared more effective than other chemotherapy regimens.