Cost effectiveness of neoadjuvant chemotherapy followed by interval cytoreductive surgery versus primary cytoreductive surgery for patients with advanced stage ovarian cancer during the initial treatment phase.

OBJECTIVE: Advanced stage epithelial ovarian cancer (AEOC) can be treated with either neoadjuvant chemotherapy (NACT) or primary cytoreductive surgery (PCS). Although randomized controlled trials show that NACT is non-inferior in overall survival compared to PCS, there may be improvement in short-term morbidity. We sought to investigate the cost-effectiveness of NACT relative to PCS for AEOC from the US Medicare perspective. METHODS: A cost-effectiveness analysis using a Markov model with a 7-month time horizon comparing (1) 3cycles of NACT with carboplatin and paclitaxel (CT), followed by interval cytoreductive surgery, then 3 additional cycles of CT, or (2) PCS followed by 6cycles of CT. Input parameters included probability of chemotherapy complications, surgical complications, treatment completion, treatment costs, and utilities. Model outcomes included costs, life-years gained, quality-adjusted life-years (QALYs) gained, and incremental cost-effectiveness ratios (ICER), in terms of cost per life-year gained and cost per QALY gained. We accounted for differences in surgical complexity by incorporating the cost of additional procedures and the probability of undergoing those procedures. Probabilistic sensitivity analysis (PSA) was performed via Monte Carlo simulations. RESULTS: NACT resulted in a savings of $7034 per patient with a 0.035 QALY increase compared to PCS; therefore, NACT dominated PCS in the base case analysis. With PSA, NACT was the dominant strategy more than 99% of the time. CONCLUSIONS: In the short-term, NACT is a cost-effective alternative compared to PCS in women with AEOC. These results may translate to longer term cost-effectiveness; however, data from randomized control trials continues to mature.

Exploring the impact of income and race on survival for women with advanced ovarian cancer undergoing primary debulking surgery at a high-volume center.

OBJECTIVE: To evaluate patients with advanced ovarian cancer (OC) undergoing primary debulking surgery (PDS) at a high-volume center (HVC), to determine whether socio-demographic disparities in PDS outcome and overall survival (OS) were present. METHODS: All patients with stages IIIB-IV high-grade OC undergoing PDS at our institution from 1/2001-12/2013 were identified. Patients self-identified race/ethnicity as non-Hispanic White (NHW), non-Hispanic Black (NHB), Asian (A), or Hispanic (H). Income level for the entire cohort was estimated using the census-reported income level for each patient's zip code as a proxy for SES. Main outcome measures were PDS outcome and median OS. Cox proportional hazards model was used to examine differences in OS by racial/ethnic and income category, controlling for selected clinical factors. RESULTS: 963 patients were identified for analysis: 855 NHW; 43 A, 34H, 28 NHB, and 3 unknown. PDS outcome was not significantly different among NHB and H as compared to NHW. Compared to NHW, Asians were more likely to have >1cm residual (AOR 2.32, 95%CI 1.1-4.9, p=0.03). Median income for the entire cohort was $85,814 (range $10,926-$231,667). After adjusting for significant prognostic factors, there were no significant differences in PDS outcome between income groups (p=0.7281). Median OS was 55.1mos (95%CI 51.8-58.5) with no significant differences in OS between the income (p=0.628) or racial/ethnic (p=0.615) groups. CONCLUSION: Statistically significant socio-demographic disparities in PDS and survival outcomes were not observed among women with advanced OC treated at this HVC. Increased efforts are needed to centralize care to and increase the diversity of pts treated at HVCs.

Cost-effectiveness analysis of dose-dense versus standard intravenous chemotherapy for ovarian cancer: An economic analysis of results from the Gynecologic Oncology Group protocol 262 randomized controlled trial.

OBJECTIVES: To determine the cost-effectiveness of dose-dense versus standard intravenous adjuvant chemotherapy for ovarian cancer using results from the no-bevacizumab cohort of the Gynecologic Oncology Group protocol 262 (GOG-262) randomized controlled trial, which reported a smaller absolute progression-free survival (PFS) benefit than the prior Japanese trial. METHODS: A three-state Markov decision model from a healthcare system perspective with a 21day cycle length and 28month time-horizon was used to calculate incremental cost-effectiveness ratio (ICER) values per progression-free life-year saved (PFLYS) using results from GOG-262. Costs of chemotherapy, complications, and surveillance were from Medicare or institutional data. PFS, discontinuation, and complication rates were from GOG-262. Time-dependent transition probabilities and within-cycle corrections were used. One-way and probabilistic sensitivity analyses were performed. RESULTS: The model produces standard and dose-dense cohorts with 84.3% and 68.3% progression event proportions at 28months, matching GOG-262 rates at the trial's median follow-up. With a median PFS of 10.3months after standard chemotherapy and a hazard ratio for progression of 0.62 after dose-dense therapy, the ICER for dose-dense chemotherapy is $8074.25 (95% confidence interval: $7615.97-$10,207.16) per PFLYS. ICER estimates are sensitive only to the hazard ratio estimate but do not exceed $100,000 per PFLYS. 99.8% of ICER estimates met a more stringent willingness-to-pay of $50,000 per PFLYS. The willingness-to-pay value at which there is a 90% probability of dose-dense treatment being cost-effective is $12,000 per PFLYS. CONCLUSIONS: Dose-dense adjuvant chemotherapy is robustly cost-effective for advanced ovarian cancer from a healthcare system perspective based on results from GOG-262.

A Cost-Effectiveness Evaluation of Germline BRCA1 and BRCA2 Testing in UK Women with Ovarian Cancer.

OBJECTIVES: To evaluate the long-term cost-effectiveness of germline BRCA1 and BRCA2 (collectively termed "BRCA") testing in women with epithelial ovarian cancer, and testing for the relevant mutation in first- and second-degree relatives of BRCA mutation-positive individuals, compared with no testing. Female BRCA mutation-positive relatives of patients with ovarian cancer could undergo risk-reducing mastectomy and/or bilateral salpingo-oophorectomy. METHODS: A cost-effectiveness model was developed that included the risks of breast and ovarian cancer; the costs, utilities, and effects of risk-reducing surgery on cancer rates; and the costs, utilities, and mortality rates associated with cancer. RESULTS: BRCA testing of all women with epithelial ovarian cancer each year is cost-effective at a UK willingness-to-pay threshold of £20,000/quality-adjusted life-year (QALY) compared with no testing, with an incremental cost-effectiveness ratio of £4,339/QALY. The result was primarily driven by fewer cases of breast cancer (142) and ovarian cancer (141) and associated reductions in mortality (77 fewer deaths) in relatives over the subsequent 50 years. Sensitivity analyses showed that the results were robust to variations in the input parameters. Probabilistic sensitivity analysis showed that the probability of germline BRCA mutation testing being cost-effective at a threshold of £20,000/QALY was 99.9%. CONCLUSIONS: Implementing germline BRCA testing in all patients with ovarian cancer would be cost-effective in the United Kingdom. The consequent reduction in future cases of breast and ovarian cancer in relatives of mutation-positive individuals would ease the burden of cancer treatments in subsequent years and result in significantly better outcomes and reduced mortality rates for these individuals.

Examining the Effects of Time to Diagnosis, Income, Symptoms, and Incidental Detection on Overall Survival in Epithelial Ovarian Cancer: Manitoba Ovarian Cancer Outcomes (MOCO) Study Group.

OBJECTIVE: The primary objectives of this study were to analyze data on time to diagnosis and correlate this with overall survival. We secondarily analyzed the effects of emergency room visits, symptoms, incidental findings, residence, socioeconomic status, and residual disease on overall survival. METHODS: This retrospective population-based descriptive cohort study examined all invasive ovarian cancer cases in Manitoba, Canada, between 2004 and 2010. Clinicopathologic, socioeconomic, and outcome data were collected. Analysis was performed with Cox and logistic regression stratified by early and late stage. RESULTS: Six hundred eighty-seven ovarian cancer patients were identified, with a final cohort of 601 patients: 210 with early-stage (1/2) and 391 with late-stage (3/4) disease. No presenting symptoms were associated with survival outcome. Poorer survival was associated with increasing age (P = 0.0016) and neoadjuvant chemotherapy (P = 0.0037). Higher income within the urban setting was also associated with a survival advantage (P = 0.0037), whereas initial presentation to the emergency room (P = 0.0399) was associated with decreased survival. Finally, for advanced-stage disease, incidental diagnosis had a significantly improved overall survival (hazard ratio, 0.424; 95% confidence interval, 0.27-0.67; P = 0.0003), even when accounting for confounding factors. Time from first presentation to diagnosis was associated with survival (P = 0.0309). CONCLUSIONS: This study found that time to diagnosis did not negatively impact overall survival, although there was an association. Age, morphology, treatment type, residual disease, medical comorbidities, and income were significant prognostic factors. This is the first study to show a survival advantage to incidentally finding an ovarian cancer. Further research is needed on the outcomes of pelvic examination.

Outcomes and Cost Analysis of Surveillance Strategies After Initial Treatment for Women With Recurrent Ovarian Cancer.

OBJECTIVE: The aim of this study was to determine whether there is a survival or cost benefit dependent on detection strategy of recurrent ovarian cancer (ie, imaging, physical examination findings, report of symptoms, or rising cancer antigen 125 [CA-125] levels). METHODS/MATERIALS: A retrospective chart review of 112 ovarian cancer patients was conducted, and method of detection of recurrent disease was determined from medical records. The following primary outcomes were determined using Cox proportional hazards regression model: progression-free survival (PFS) after diagnosis of recurrence and time to death after diagnosis of recurrence (overall survival [OS]). Several approaches to disease surveillance were proposed, and a cost model was applied. RESULTS: Median time to recurrence was 13.5 months. Overall, 6.3% presented with only physical examination findings; 24.1%, with elevating CA-125 levels; 34.8%, with imaging; and 32.1%, with symptoms. Most patients presenting with recurrent disease diagnosed by rising CA-125 were white (62.9%); those with imaging and symptomatic recurrences were blacks (56.4% and 57.1%, respectively). There was a small but not statistically significant OS benefit for recurrence detected via CA-125 (P = 0.85; OS per detection method: PE, 20.7 months; CA-125, 26.8 months; imaging, 17.8 months; and symptoms, 6.6 months). We modeled costs of surveillance in our patient cohort; up to 40.8% of cases of ovarian cancer recurrences would have been missed if no imaging were obtained during surveillance. CONCLUSIONS: Results indicate minimal differences in PFS and statistically insignificant differences in OS, depending on detection method. Notably, black patients with Medicaid presented most often with symptomatic recurrences, which surprisingly did not affect patient OS and PFS; and interestingly, pr\ivate or self-pay insurance was associated with decreased OS among black patients. From our cost analysis, we estimate that the most cost-effective surveillance strategy for the first year costs $9.2 million annually and includes office visit biannually, biannual CA-125 levels, and annual asymptomatic imaging.

The Pharmacological Costs of Second-Line Treatments for Recurrent Ovarian Cancer.

INTRODUCTION: In ovarian cancer, it is uncertain which chemotherapy regimen is more clinically effective and cost-effective for the treatment of recurrence; therefore, it might be interesting to make a balance between the cost of the drugs administered and the difference in progression-free survival (PFS) and overall survival (OS). METHODS: The present evaluation was restricted to pivotal phase 3 randomized controlled trials. We calculated the pharmacological costs necessary to get the benefit in PFS and OS. The costs of drugs are at the pharmacy of our hospital and are expressed in Euros (&OV0556;). We have subsequently applied the European Society for Medical Oncology Magnitude of Clinical Benefit Scale. RESULTS: Our study evaluated 3 phase 3 randomized controlled trials, including 2004 patients. The most relevant increase of costs was associated with the combination chemotherapy including trabectedin, with the highest costs for month of PFS gained (15,836 &OV0556;) and for month of OS gained (7198 &OV0556;), but it substantially differs considering the data of partially platinum-sensitive populations (platinum-free interval of 6-12 months), with 3959 &OV0556; for month of OS gained. CONCLUSIONS: The addition of trabectedin to pegylated liposomal doxorubicin for the treatment of recurrent ovarian cancer can lead to an increase of pharmacological costs. Differently, considering OS in patients with platinum-free interval of 6 to 12 months, there is a halving of pharmacological costs with the addition of trabectedin to pegylated liposomal doxorubicin. These costs are in line with the spending suggested as sustainable (thresholds of <$61,500 per life-year gained).

A cost-effectiveness analysis of a chemoresponse assay for treatment of patients with recurrent epithelial ovarian cancer.

OBJECTIVE: Clinical validation of a chemoresponse assay was recently published, demonstrating a significant increase in overall survival in recurrent ovarian cancer patients treated with therapies to which their tumor was sensitive in the assay. The current study investigates the cost effectiveness of using the assay at the time of ovarian cancer recurrence from the payer's perspective. METHODS: Using a Markov state transition model, patient characteristics and survival data from the recent clinical study, the cumulative costs over the study horizon (71 months) for both the baseline (no assay) and intervention (assay consistent, hypothetical) cohorts were evaluated. RESULTS: The assay consistent cohort had an incremental cost effectiveness ratio (ICER) of $6206 per life year saved (LYS), as compared to the baseline cohort. Cost-effectiveness was further demonstrated in platinum-sensitive and platinum-resistant populations treated with assay-sensitive therapies, with ICERs of $2773 per LYS and $2736 per LYS, respectively. CONCLUSIONS: The use of a chemoresponse assay to inform treatment decisions in recurrent ovarian cancer patients has the potential to be cost-effective in both platinum-sensitive and platinum-resistant patients.

Socioeconomic status as a predictor of adherence to treatment guidelines for early-stage ovarian cancer.

OBJECTIVE: Investigate the impact of socioeconomic status and other demographic variables on adherence to the National Comprehensive Cancer Network ovarian cancer treatment guidelines among patients with stage I/II disease. METHODS: Patients diagnosed with stage I/II epithelial ovarian cancer between 1/1/96-12/31/06 were identified from the California Cancer Registry. Univariate analysis and multivariate logistic regression models were used to evaluate differences in surgical procedures, chemotherapy regimens, and overall adherence to the NCCN guidelines according to increasing SES quintiles (SES-1 to SES-5). RESULTS: A total of 5445 stage I and II patients were identified. The median age at diagnosis was 54.0years (range=18-99years); 72.5% of patients had stage I disease, while 27.5% had stage II disease. With a median follow-up time of 5years, the 5-year ovarian cancer-specific survival for all patients was 82.7% (SE=0.6%). Overall, 23.7% of patients received care that was adherent to the NCCN guidelines. Compared to patients in the highest SES quintile (SES-5), patients in the lowest SES quintile (SES-1) were significantly less likely to receive proper surgery (27.3% vs 47.9%, p<0.001) or chemotherapy (42.4% vs 53.6%, p<0.001). There were statistically significant trends between increasing SES and the likelihood of overall treatment plan adherence to the NCCN guidelines: SES-1=16.4%, SES-2=19.0%, SES-3=22.4%, SES-4=24.2% and SES-5=31.6% (p<0.001). Multivariate logistic regression analysis revealed that compared to SES-5, decreasing SES was independently predictive of a higher risk of non-standard overall care. CONCLUSIONS: For patients with early-stage ovarian cancer, low SES is a significant and independent predictor of deviation from the NCCN guidelines for surgery, chemotherapy, and overall treatment.

Costs of treatment for elderly women with advanced ovarian cancer in a Medicare population.

OBJECTIVE: To analyze the cost of treating women with advanced stage epithelial ovarian cancer (EOC) undergoing primary debulking surgery (PDS) or neo-adjuvant chemotherapy (NACT). METHODS: The Surveillance, Epidemiology, and End Results (SEER) - Medicare database (1992 to 2009) was used to evaluate the 7-month cost of care following PDS and NACT for advanced EOC. Multivariate analyses were used to evaluate differences between women treated by PDS and NACT on cost and survival. RESULTS: Of the 4506 women eligible for analysis, 82.4% underwent PDS and 17.6% received NACT. Eighty-five percent with stage IIIC and 78.5% with stage IV EOC underwent PDS (p<0.0001). No significant difference in the median cost of care between PDS and NACT existed in women with stage IIIC EOC ($59,801 vs. $59,905). There was a 12% increase in adjusted cost of care for stage IV patients ($63,131 vs. $55,302) who received PDS (p<0.0001). Increasing Charlson score was associated with an increase in 7-month cost of care in both stages. NACT was associated with a decreased 5-year overall survival in women with stage IIIC EOC (HR=1.27, 95% CI: 1.10-1.47) and stage IV EOC (HR=1.19, 95% CI: 1.03-1.37) compared to PDS. CONCLUSION: NACT and PDS are comparable in cost for women with stage IIIC EOC, and PDS is minimally more expensive for women with stage IV EOC. PDS was associated with an increase 5-year overall survival. Future investigations should include cost-effectiveness analyses where additional measures such as quality adjusted life years and propensity scored survival are included.

Cost-utility comparison of neoadjuvant chemotherapy versus primary debulking surgery for treatment of advanced-stage ovarian cancer in patients 65 years old or older.

OBJECTIVE: Treatment for advanced-stage epithelial ovarian cancer (AEOC) includes primary debulking surgery (PDS) or neoadjuvant chemotherapy (NACT). A randomized controlled trial comparing these treatments resulted in comparable overall survival (OS). Studies report more complications and lower chemotherapy completion rates in patients 65 years old or older receiving PDS. We sought to evaluate the cost implications of NACT relative to PDS in AEOC patients 65 years old or older. STUDY DESIGN: A 5 year Markov model was created. Arm 1 modeled PDS followed by 6 cycles of carboplatin and paclitaxel (CT). Arm 2 modeled 3 cycles of CT, followed by interval debulking surgery and then 3 additional cycles of CT. Parameters included OS, surgical complications, probability of treatment initiation, treatment cost, and quality of life (QOL). OS was assumed to be equal based on the findings of the international randomized control trial. Differences in surgical complexity were accounted for in base surgical cost plus add-on procedure costs weighted by occurrence rates. Hospital cost was a weighted average of diagnosis-related group costs weighted by composite estimates of complication rates. Sensitivity analyses were performed. RESULTS: Assuming equal survival, NACT produces a cost savings of $5616. If PDS improved median OS by 1.5 months or longer, PDS would be cost effective (CE) at a $100,000/quality-adjusted life-year threshold. If PDS improved OS by 3.2 months or longer, it would be CE at a $50,000 threshold. The model was robust to variation in costs and complication rates. Moderate decreases in the QOL with NACT would result in PDS being CE. CONCLUSION: A model based on the RCT comparing NACT and PDS showed NACT is a cost-saving treatment compared with PDS for AEOC in patients 65 years old or older. Small increases in OS with PDS or moderate declines in QOL with NACT would result in PDS being CE at the $100,000/quality-adjusted life-year threshold. Our results support further evaluation of the effects of PDS on OS, QOL and complications in AEOC patients 65 years old or older.

Socioeconomic status and epithelial ovarian cancer survival in Sweden.

PURPOSE: To investigate socioeconomic disparities in epithelial ovarian cancer (EOC) survival in Sweden. METHODS: A cohort of 635 women with invasive EOC who participated in a nationwide population-based case-control study was included in the present population-based prospective study. Women were diagnosed with EOC between 1993 and 1995. Mortality until 31 December 2007 was determined through linkage with the Swedish Cause of Death Registry. Clinical data (tumor stage and tumor differentiation) and indicators of socioeconomic status (SES, education level, and annual individual disposable income) were retrieved from medical records and a nationwide database, respectively. The Cox proportional hazards regression model and the Laplace regression model were used to estimate the effect of clinical factors and SES on EOC survival. RESULTS: The main factors associated with EOC survival were tumor stage and tumor differentiation: women with stage II, III, and IV tumors had a greater mortality risk than those with stage I tumors [hazard ratio (HR) 2.65, 95 % confidence interval (CI) 1.73-4.07; HR 6.69, 95 % CI 4.85-9.22; HR 12.84, 95 % CI 8.90-18.66, respectively]. After adjustment for these tumor characteristics, no clear association remained between our indicators of SES and EOC survival, but better survival was observed among women with stage IV tumors and a higher income level, and among women with poorly differentiated tumors and a higher education level. Nevertheless, there was no evidence of extended survival among women with higher compared to lower SES. CONCLUSIONS: Our study provides no convincing evidence of an association between SES and EOC survival in Sweden.

The association between neighborhood socioeconomic status and ovarian cancer tumor characteristics.

PURPOSE: Higher pathologic grade, suboptimal debulking surgery, and late-stage are markers of more aggressive and advanced ovarian cancer. Neighborhood socioeconomic status (SES) has been associated with more aggressive and advanced tumors for other cancer sites, and this may also be true for ovarian cancer. METHODS: We examined the association between neighborhood SES and ovarian cancer tumor characteristics using data on 581 women diagnosed with epithelial ovarian cancer in Cook County, Illinois. Two complementary measures (concentrated disadvantage and concentrated affluence) were used to estimate neighborhood SES. Prevalence differences and 95 % confidence intervals were estimated in logistic regression models adjusted for age and race. RESULTS: Greater disadvantage was associated with higher grade tumors (p = 0.03) and suboptimal debulking (p = 0.05) and marginally associated with later tumor stage (p = 0.20). Greater affluence was inversely associated with stage at diagnosis (p = 0.004) and suboptimal debulking (p = 0.03) and (marginally) with tumor grade (p = 0.21). CONCLUSION: Our findings suggest that lower SES, estimated by neighborhood SES, is associated with ovarian cancer tumor characteristics indicative of more advanced and aggressive disease.

Cost-effectiveness of adding bevacizumab to first line therapy for patients with advanced ovarian cancer.

OBJECTIVE: To evaluate, from a societal perspective, the cost-effectiveness of adding bevacizumab to first-line therapy based on outcomes from the GOG-218 and ICON-7 trials. METHODS: A three-state Markov model was used. The time horizon was until the death of 99% of the initial cohort of 1000 individuals. Costs and quality-adjusted life-years (QALYs) were discounted at an annual rate of 3%. All costs were adjusted to 2013 USD. The incremental cost-effectiveness ratio (ICER) was reported as incremental cost per QALY gained. The robustness of the result was checked with one-way sensitivity analyses and for relevant clinical situations (i.e. varying the drug of choice to treat cancer recurrence). Subgroup analysis was conducted to identify subgroup of population for whom the strategy could be cost-effective. The potential impact of biosimilar bevacizumab was considered, using a 30% price reduction. RESULTS: For the GOG-218 study protocol, widely followed in US, the addition of bevacizumab results in an ICER of $2,420,691/QALY. For the ICON-7 study protocol, the ICER is $225,515/QALY. The results of the model were sensitive to the quality of life (QoL) and the median progression free survival (PFS). Biosimilar bevacizumab didn't reduce cost sufficiently to change conclusions. First-line augmentation is cost-effective, with biosimilar bevacizumab, for stage IV patients ($126,169/QALY), ECOG PS1 patients ($116,575/QALY) and for patients with suboptimal residual disease ($122,822/QALY) as per the ICON-7 protocol. CONCLUSION: Addition of bevacizumab, by in large, is cost-ineffective. It can become cost-effective with the ICON-7 protocol, in patients at high risk of progression using biosimilar bevacizumab.

Cost-effectiveness of early-initiated treatment for advanced-stage epithelial ovarian cancer patients: a modeling study.

OBJECTIVE: Between diagnosis and primary treatment of patients with epithelial ovarian cancer (EOC), gaps of several weeks exist. Reducing these time intervals may benefit the patient and may lead to a reduction of costs. We explored the cost-effectiveness of early-initiated treatment of patients with suspected advanced-stage EOC compared with that of current treatment. METHODS: A discrete event simulation was used to synthesize all available evidences and to evaluate the health care costs and effects (quality-adjusted life years [QALYs]) of the 2 treatment strategies over lifetime. Overall survival, progression-free survival, health-related quality of life, and costs of the separate events were assumed to remain equal. Other uncertainties were addressed using deterministic and probabilistic sensitivity analyses. RESULTS: The treatment times of current and early-initiated treatment were 27 and 24 weeks, respectively. Early-initiated treatment yielded 3.42 QALYs per patient, for a total expected health care cost of €25,654. Current treatment yielded 3.40 QALYs per patient, for a total expected health care cost of €25,607. This resulted in an incremental cost-effectiveness ratio of €2592 per QALY gained for early-initiated treatment compared with that for current treatment. For the willingness to pay for €30,000 or more per QALY, early-initiated treatment had a 100% probability of being cost-effective compared with current treatment under the previously mentioned assumptions. CONCLUSIONS: Given the current evidence, early-initiated treatment of patients with suspected advanced-stage EOC leads to additional QALYs and seems to be cost-effective compared with current treatment.

Trends in treatment of advanced epithelial ovarian cancer in the Medicare population.

OBJECTIVE: Optimal care for most patients with advanced ovarian cancer generally includes both surgery and chemotherapy. Little is known about the proportion of women in the US who receive combination care or the sequence in which this care is delivered. This study evaluated patterns of care, frequency of completion of recommended therapy and factors associated with sequencing of therapy. METHODS: Using the Surveillance, Epidemiology and End-Results data we identified a cohort of 8211 women aged 65 and above with stage III/IV epithelial ovarian cancer diagnosed between 1995 and 2005. Receipt of chemotherapy or surgery was identified using Medicare claims. Logistic regression was used to evaluate factors associated with sequencing of treatment and the receipt of surgery. RESULTS: 3241 (39.1%) had surgery and at least 6 cycles of chemotherapy in either order. Surgery was performed initially in 4827 (58.8%) women and 3658/4827 (75.8%) had subsequent chemotherapy. 2017 (24.6%) had primary chemotherapy and 649/2017 (32.2%) of these women had subsequent surgery. Advanced age, African American race, stage IV disease, non-married status and increasing medical comorbidity were all associated with the failure to receive both surgery and at least 6 cycles of chemotherapy (all p<0.01). CONCLUSIONS: The majority of women with advanced ovarian cancer in the Medicare population do not receive both combination therapy with surgery and at least 6 cycles of chemotherapy. A large proportion of women are receiving chemotherapy as primary treatment for advanced ovarian cancer, and the majority of these patients do not have cancer-directed surgery.

Consolidation paclitaxel is more cost-effective than bevacizumab following upfront treatment of advanced epithelial ovarian cancer.

INTRODUCTION: Randomized trials have demonstrated significant improvements in progression-free survival (PFS) with consolidation paclitaxel (P) and bevacizumab (B) following cytoreduction and adjuvant carboplatin/paclitaxel (CP) for advanced epithelial ovarian cancer (EOC). We sought to evaluate the cost-effectiveness (C/E) of these consolidation strategies. METHODS: A decision model was developed based on Gynecologic Oncology Group (GOG) protocols #178 and #218. Arm 1 is 6 cycles of CP. Arm 2 is 6 cycles of CP followed by 12 cycles of P (CP+P). Arm 3 is 1 cycle of CP, 5 cycles of CPB, and 16 cycles of B (CPB+B). Parameters include PFS, overall survival (OS), cost, complications (neuropathy for P and bowel perforation for B), and quality-of-life utility values. Sensitivity analyses were performed. RESULTS: The incremental cost-effectiveness ratio (ICER) for CT+T is $13,402/quality adjusted life year (QALY) gained compared to CP. For CPB+B compared to CP, the ICER is $326,530/QALY. When compared simultaneously, CPB+B is dominated, i.e. is more costly and less effective than CP+P. Results were robust to parameter variation. At a willingness to pay threshold of $100,000/QALY, CP+P was the preferred option throughout most of the decision space. Sensitivity analyses suggest that CPB+B would become the preferred option if it were to improve OS by 6.1 years over CP+P. CONCLUSIONS: In this model, B consolidation for advanced EOC was associated with a modest improvement in effectiveness that is less than that with P consolidation and more costly. A statistically significant improvement in survival may improve the value of B consolidation.

Protocol development for ovarian cancer treatment in Kenya: a brief report.

INTRODUCTION: Ovarian cancer is a leading cause of cancer death for Kenyan women. Most women are diagnosed with an advanced stage of disease. The current North American standard of care includes surgery followed by carboplatin and paclitaxel. Neither drug is available for Kenyan women. We performed a literature search investigating chemotherapy in low resource countries with the aim to write an evidence-based chemotherapy protocol for women diagnosed with ovarian cancer in Eldoret, Kenya, at the Moi Teaching and Referral Hospital. METHODS: We systematically searched PubMed and EMBASE for articles describing chemotherapy treatment outcomes of ovarian epithelial cancer in low-resource settings. After data analysis, a secondary review was undertaken on randomized controlled trials(RCTs) aligning with chemotherapy availability in Kenya. RESULTS: We identified 1184 articles. Fourteen met our criteria: ovarian epithelial cancer,low resource, chemotherapy use, and survival or response data. No publications were RCTs or had a cohort larger than 100 patients. There was no consistency in drug choice between studies. After this search, we reviewed commonly quoted and relevant RCTs and meta-analyses conducted on ovarian cancer since the 1980s. Although RCTs in the developed world suggest carboplatin and taxol provide optimal survival benefit, these drugs are unavailable in Kenya. Cyclophosphamide and cisplatin provide the next most optimal survival benefit, with acceptable and manageable toxicity. Because these drugs are more available and affordable in Kenya, we have developed a protocol recommending their use, which has been accepted by the Moi Teaching and Referral Hospital. CONCLUSIONS: Currently, there is a paucity of published RCTs that may guide treatment in low-resource settings. One considerable barrier to establishing and evaluating chemotherapy protocols in low-resource settings may be the cost of chemotherapy drugs. There needs to be an international movement to make cancer chemotherapeutics available at lower prices in low-resource settings.

Markov-modeling for the administration of platinum analogues and paclitaxel as first-line chemotherapy as well as topotecan and liposomal doxorubicin as second-line chemotherapy with epithelial ovarian carcinoma.

PURPOSE: So far there is no analysis available on the cost effectiveness of the paclitaxel/platinum-analogue combination versus carboplatin monotherapy with ovarian cancer. Up-to-now only a cost-utility analysis on ovarian carcinoma has been published (Ortega et al. in Gynecol Oncol 66(3):454-463, 1997), which in addition to the first-line chemotherapy included second-line chemotherapy with effectiveness and cost data in the analysis. Therefore, within the scope of our study the cost effectiveness of platinum analogues and paclitaxel as first-line chemotherapy as well as topotecan and liposomal doxorubicin as second-lie chemotherapy was to be determined with epithelial ovarian carcinoma. METHODS: For this purpose a decision-making Markov model was developed which represents the medical and economic consequences of the administration of paclitaxel and platinum derivatives in first-line chemotherapy and the administration of topotecan and liposomal doxorubicin in second-line chemotherapy in the treatment of epithelial ovarian carcinoma by means of data from the literature. Patients were treated either in the early (FIGO stage I-IIa) or advanced stage (FIGO stage IIb-IV). RESULTS: The therapeutic strategy caboplatin followed by topotecan costs 20,123.91 euros, the therapeutic strategy carboplatin followed by liposomal doxorubicin 22,336.57 euros, the therapeutic strategy carboplatin/pactlitaxel followed by liposomal topotecan 29,820.64 euros and the therapeutic strategy carboplatin/paclitaxel followed by liposomal doxorubicin 31,560.47 euros from the time of diagnosis until death or survival within 5 years. With lives saved, accordingly of 2.55, 2.70, 2.60 and 2.65 years' costs amounted to 7,891 euros, 8,270.35 euros, and 11,453.62 euros per year of life saved. CONCLUSIONS: Based on the threshold value of social willingness to pay 45,500 euros per year of life saved, the therapeutic strategy carboplatin followed by topotecan, the therapeutic strategy carboplatin followed by liposomal doxorubicin, the therapeutic strategy carboplatin/paclitaxel followed by topotcan and the therapeutic strategy carboplatin/paclitaxel followed by liposomal doxorubicin can be evaluated to be cost effective.