Quality-adjusted Survival Research Articles

ES02.01 Expanding PROs in Daily Practice

ES02.01 Expanding PROs in Daily Practice

Long-term quality-adjusted survival following therapeutic bronchoscopy for malignant central airway obstruction

BackgroundWhile therapeutic bronchoscopy has been used to treat malignant central (CAO) airway obstruction for >25 years, there are no studies quantifying the impact of therapeutic bronchoscopy on long-term quality-adjusted survival.MethodsWe...

Addition of Docetaxel to First-line Long-term Hormone Therapy in Prostate Cancer (STAMPEDE): Modelling to Estimate Long-term Survival, Quality-adjusted Survival, and Cost-effectiveness

BackgroundResults from large randomised controlled trials have shown that adding docetaxel to the standard of care (SOC) for men initiating hormone therapy for prostate cancer (PC) prolongs survival for those with metastatic disease and prolongs failure-free survival for those without. To date there has been no formal assessment of whether funding docetaxel in this setting represents an appropriate use of UK National Health Service (NHS) resources. ObjectiveTo assess whether administering docetaxel to men with PC starting long-term hormone therapy is cost-effective in a UK setting. Design, setting, and participantsWe modelled health outcomes and costs in the UK NHS using data collected within the STAMPEDE trial, which enrolled men with high-risk, locally advanced metastatic or recurrent PC starting first-line hormone therapy. InterventionSOC was hormone therapy for ≥2 yr and radiotherapy in some patients. Docetaxel (75mg/m2) was administered alongside SOC for six three-weekly cycles. Outcome measurements and statistical analysisThe model generated lifetime predictions of costs, changes in survival duration, quality-adjusted life years (QALYs), and incremental cost-effectiveness ratios (ICERs). Results and limitationsThe model predicted that docetaxel would extend survival (discounted quality-adjusted survival) by 0.89 yr (0.51) for metastatic PC and 0.78 yr (0.39) for nonmetastatic PC, and would be cost-effective in metastatic PC (ICER £5514/QALY vs SOC) and nonmetastatic PC (higher QALYs, lower costs vs SOC). Docetaxel remained cost-effective in nonmetastatic PC when the assumption of no survival advantage was modelled. ConclusionsDocetaxel is cost-effective among patients with nonmetastatic and metastatic PC in a UK setting. Clinicians should consider whether the evidence is now sufficiently compelling to support docetaxel use in patients with nonmetastatic PC, as the opportunity to offer docetaxel at hormone therapy initiation will be missed for some patients by the time more mature survival data are available. Patient summaryStarting docetaxel chemotherapy alongside hormone therapy represents a good use of UK National Health Service resources for patients with prostate cancer that is high risk or has spread to other parts of the body.

Quality-adjusted survival of nivolumab plus ipilimumab or nivolumab alone versus ipilimumab alone among treatment-naive patients with advanced melanoma: a quality-adjusted time without symptoms or toxicity (Q-TWiST) analysis.

To compare the quality-adjusted survival of nivolumab plus ipilimumab combination and nivolumab alone versus ipilimumab alone among treatment-naive patients with advanced melanoma based on a minimum 36-month follow-up from the CheckMate 067 trial. Overall survival was partitioned into time without symptoms of progression or toxicity (TWiST), time with treatment-related grade ≥ 3 adverse events after randomization but before progression (TOX), and time from progression until end of follow-up or death (REL). Mean quality-adjusted TWiST (Q-TWiST) was calculated by multiplying the mean time spent in each health state by a utility of 1.0 for TWiST and 0.5 for TOX and REL. Sensitivity analyses included varying utilities of TOX and REL; Q-TWiST gains at different follow-up times were calculated using EQ-5D-3L utilities from the trial. Relative Q-TWiST gain of ≥ 10% was considered clinically important. Compared with ipilimumab-treated patients, those who received nivolumab + ipilimumab combination had significantly longer TWiST and TOX but shorter REL; nivolumab-treated patients had significantly longer TWiST, shorter REL, and shorter but statistically nonsignificant TOX. Mean Q-TWiST was highest for nivolumab + ipilimumab (23.5months; 95% CI 21.9-25.2), followed by nivolumab (21.8months; 95% CI 20.2-23.4) and ipilimumab (15.3months; 95% CI 13.9-16.6). Relative Q-TWiST gains were favorable and clinically important for nivolumab + ipilimumab combination (+ 36.81%) and nivolumab alone (+ 29.18%) versus ipilimumab alone. Relative gains increased with follow-up from 3 to 40months for all comparisons. These gains remained consistent in magnitude and direction in the different sensitivity analyses. Nivolumab + ipilimumab combination and nivolumab alone resulted in a statistically significant and clinically important improvement in quality-adjusted survival compared with ipilimumab alone.

Study Protocol of the NVALT25-ELDAPT Trial: Selecting the Optimal Treatment for Older Patients With Stage III Non–small-cell Lung Cancer

BackgroundPatients aged 75 years or older with stage III non–small-cell lung cancer (NSCLC) are underrepresented in clinical trials, leading to a lack of evidence for selection of the optimal treatment strategy. Information on benefits and harms of concurrent chemoradiotherapy among medically fit elderly patients is largely unknown, and reliable tools are needed to distinguish fit from frail patients for treatment selection. Also, information regarding quality of life during and after treatment is scarce. Patients and MethodsThis multicenter NVALT25-ELDAPT (Dutch Association of Chest Physicians Trial Number 25 - Elderly with locally advanced Lung cancer: Deciding through geriatric Assessment on the oPtimal Treatment strategy) trial (NCT02284308) consists of a phase III randomized trial in combination with an observational study for all patients who do not participate in the randomized trial. The first aim of this study is to develop a reliable and clinically applicable screening tool to distinguish medically fit from frail patients. All patients ≥ 75 years diagnosed with stage III NSCLC are invited to undergo extensive geriatric assessment (part I). The second aim is to compare treatment tolerance, survival, and quality of life between concurrent and sequential chemoradiotherapy in fit patients (randomized trial, part II). For all patients, overall survival adjusted for quality of life (quality-adjusted survival) is described for each category of fitness and treatment strategy during and after treatment. ConclusionWith the results of the NVALT25-ELDAPT trial, treatment selection can be optimized and the best possible outcomes for each individual older patient with stage III NSCLC can be achieved.

Abstract LB-257: Tumor treating fields treatment for patients with newly diagnosed glioblastoma: A cost-effectiveness analysis

Abstract Objective: To estimate the potential cost-effectiveness of treating newly diagnosed glioblastoma patients with tumor treating fields (TTFields) and temozolomide (TMZ) based on data from the final analysis of the EF-14 Trial. Background: Glioblastoma (GBM) is the most aggressive form of primary brain cancer in adults. The EF-14 Trial in GBM patients reported a 5-year survival rate of 13% for newly diagnosed GBM patients treated with TTFields and maintenance temozolomide (TMZ) chemotherapy. The cost-effectiveness of adding TTFields to the maintainance phase of the first line treatment protocol for GBM patients has not been previously assessed from a U.S. health system perspective. Methods: The primary economic endpoint was the projected incremental cost-effectiveness ratio (ICER) for treatment of newly diagnosed GBM with TTFields and TMZ versus TMZ monotherapy alone during the maintenance phase of treatment. Patient outcomes were simulated using a 3-state area under the curve model including alive without progression, progressed disease, and death. Survival was modelled over a lifetime horizon by integrating the 5-year survival results reported in the EF-14 trial with long-term GBM epidemiology data and U.S. background mortality rates. Data on patient utilities used to calculate quality-adjusted life years (QALYs) were based on a previous analysis of GBM-specific health-state preferences. Costs and frequency of adverse events associated with TTFields and TMZ were estimated from the EF-14 trial. Supportive care cost estimates were derived from published literature. Future survival benefits and costs were discounted to present value at a rate of 3%. One-way and probabilistic sensitivity analyses were performed to assess result uncertainty due to parameter variability. Results: Use of TTFields plus TMZ were projected to increase in undiscounted mean survival of 1.8 life years versus TMZ alone. The resulting life years gained (LYG) and quality-adjusted life years (QALYs) were 1.3 and 1.0, respectively, after discounting. The incremental total cost was $188,870. The ICER was $150,638 per LYG and $198,032 per QALY gained. The probability of TTFields being cost-effective was 70.5% at a willingness-to-pay threshold of $200,000 per QALY. Conclusions: Treating newly diagnosed GBM patients with TTFields and TMZ has the potential to increase mean lifetime survival and quality-adjusted survival substantially compared to treatment with TMZ alone. TTFields therapy, even when evaluated at its full list price, demonstrated a high probability of cost-effectiveness at a willingness to pay threshold of $200,000. Citation Format: Gregory F. Guzauskas, Erqi L. Pollom, Volker W. Stieber, Bruce C. Wang, Lou Garrison. Tumor treating fields treatment for patients with newly diagnosed glioblastoma: A cost-effectiveness analysis [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr LB-257.

Three Lymphadenectomy Strategies in Low-Risk Endometrial Carcinoma

To evaluate the cost-utility of three lymphadenectomy strategies in the management of low-risk endometrial carcinoma. A decision analysis model compared three lymphadenectomy strategies in women undergoing minimally invasive surgery for low-risk endometrial carcinoma: 1) routine lymphadenectomy in all patients, 2) selective lymphadenectomy based on intraoperative frozen section criteria, and 3) sentinel lymph node mapping. Costs and outcomes were obtained from published literature and Medicare reimbursement rates. Costs categories consisted of hospital, physician, operating room, pathology, and lymphedema treatment. Effectiveness was defined as 3-year disease-specific survival adjusted for the effect of lymphedema (utility=0.8) on quality of life. A cost-utility analysis was performed comparing the different strategies. Multiple deterministic sensitivity analyses were done. In the base-case scenario, routine lymphadenectomy had a cost of $18,041 and an effectiveness of 2.79 quality-adjusted life-years (QALYs). Selective lymphadenectomy had a cost of $17,036 and an effectiveness of 2.81 QALYs, whereas sentinel lymph node mapping had a cost of $16,401 and an effectiveness of 2.87 QALYs. With a difference of $1,005 and 0.02 QALYs, selective lymphadenectomy was both less costly and more effective than routine lymphadenectomy, dominating it. However, with the lowest cost and highest effectiveness, sentinel lymph node mapping dominated the other modalities and was the most cost-effective strategy. These findings were robust to multiple sensitivity analyses varying the rates of lymphedema and lymphadenectomy, surgical approach (open or minimally invasive surgery), lymphedema utility, and costs. For the estimated 40,000 women undergoing surgery for low-risk endometrial carcinoma each year in the United States, the annual cost of routine lymphadenectomy, selective lymphadenectomy, and sentinel lymph node mapping would be $722 million, $681 million, and $656 million, respectively. Compared with routine and selective lymphadenectomy, sentinel lymph node mapping had the lowest costs and highest quality-adjusted survival, making it the most cost-effective strategy in the management of low-risk endometrial carcinoma.

Cost-Effectiveness of Ventricular Assist Device Destination Therapy for Advanced Heart Failure in Duchenne Muscular Dystrophy

Destination ventricular assist device therapy (DT-VAD) is well accepted in select adults with medically refractory heart failure (HF) who are not transplant candidates; however, its use in younger patients with progressive diseases is unclear. We sought to evaluate the cost-effectiveness of DT-VAD in Duchenne muscular dystrophy (DMD) patients with advanced HF. We created a Markov-state transition model (5-year horizon) to compare survival, costs, and quality of life (QOL) between medical management and DT-VAD in DMD with advanced HF. Model input parameters were derived from the literature. We used sensitivity analyses to explore uncertainty around model assumptions. DT-VAD had higher costs ($435,602 vs. $125,696), survival (3.13 vs. 0.60years), and quality-adjusted survival (1.99 vs. 0.26years) than medical management. The incremental cost-effectiveness ratio (ICER) for DT-VAD was $179,086 per quality-adjusted life year (QALY). In sensitivity analyses that were widely varied to account for uncertainty in model assumptions, the DT-VAD strategy generally remained more costly and effective than medical management. Only when VAD implantation costs were <$113,142 did the DT-VAD strategy fall below the $100,000/QALY willingness-to-pay threshold commonly considered to be "cost-effective." In this exploratory analysis, DT-VAD for patients with DMD and advanced HF exceeded societal expectations for cost-effectiveness but had an ICER similar to the accepted practice of DT-VAD in adult HF patients. While more experience and research in this population is needed, our analysis suggests that DT-VAD for advanced HF in DMD should not be dismissed solely based on cost.

Effect of Intermittent Pneumatic Compression on Preventing Deep Vein Thrombosis Among Stroke Patients: A Systematic Review and Meta-Analysis.

Deep vein thrombosis (DVT) and subsequent pulmonary embolism (PE) are common complications of stroke. However, the effect of intermittent pneumatic compression (IPC) for patients after stroke is uncertain. To assess the effectiveness and safety of IPC in reducing the risk of DVT, PE, and mortality in stroke patients. We searched leading medical databases including Medline, EMBASE, Cochrane Library, Wanfang, CNKI, and CBM, from inception to June 2, 2017. Studies comparing IPC with no IPC in stroke patients were included. Agreement was measured using simple agreement and kappa statistics. The rates of PE, DVT, and mortality were compared. The results were pooled using a fixed effects model to evaluate the differences between the IPC and control groups. If there was significant heterogeneity in the pooled result, a random effect model was used. We identified seven randomized controlled trials that included 3,551 stroke patients. The average calculated κ for the various parameters was κ = 0.96 (0.70-1). Overall, IPC significantly reduced the incidence of DVT in stroke patients (risk ratio [RR] = 0.50; 95% confidence interval [CI 0.27, 0.94]). At the same time, IPC increased IPC-related adverse events (RR = 5.71; 95% CI [3.40, 9.58]). Though IPC was associated with a significant increase in survival by 4.5 days during 6 months of follow-up (148-152 days; 95% CI [-0.2, 9.1]), there was a mean gain of only 0.9days (26.7-27.6days; 95% CI [2.1, 3.9]) in quality-adjusted survival during the 6-month follow-up. Overall, sensitivity analyses did not alter these findings. This review provides an important basis for preventing DVT in stroke patients, especially in hemorrhagic stroke patients. IPC significantly reduces the risk of DVT and significantly improves survival in a wide variety of patients who are immobile after stroke. However, IPC does not significantly improve quality-adjusted survival. Clinicians should take functional status and quality of life into consideration when making decisions for stroke patients.

PCV44 - Giapreza For The Treatment Of Severe Distributive Shock In The Intensive Care Unit: A US Cost-Effectiveness Analysis

Distributive shock (DS) is characterized by peripheral vasodilation and reduced blood pressure despite adequate cardiac output. Patients with DS unresponsive to currently available vasopressors are at high 30-day mortality risk. Current vasopressors are also associated with significant side effects. In the ATHOS-3 Phase 3 clinical trial, addition of Giapreza to current vasopressors (SOC) was shown to increase mean arterial blood pressure (MAP) and was associated with reduced 28-day mortality in ICU patients with refractory vasodilatory shock (54% vs. 46%). The objective of this analysis is to determine the cost-effectiveness of adding Giapreza to SOC for DS in the ICU for US hospitals. A decision-analytic model was developed using the results of the ATHOS-3 trial, using the perspective of a US hospital system. Short-term mortality outcomes were based on 28-day ATHOS-3 survival rates. Lifetime projections were modeled using individually estimated life expectancies for 28-day survivors. Health state utilities were modeled using estimates for the US adult population weighted for sepsis mortality. Resource use rates were based on the clinical trial. Resource use cost was drawn from the literature and were inflated to 2017 dollars. QALYs were discounted at 3%. Sub-groups included MAP levels, prior vasopressin use, and those <65 vs. 65+ years old. Sensitivity analyses assessed model uncertainty. The base-case cost-effectiveness analyses showed an increase in survival of 0.08 lives saved with the addition of Giapreza, for an estimated $85,044 - $110,734 per life-saved. The long-term results showed an increase in quality-adjusted survival of 0.57 QALYs, with a cost of $11,576 4/QALY - $15,072/QALY. Sensitivity analyses showed that mortality, Giapreza cost, and resource use cost were primary drivers of long-term results and that the all results were robust within values tested. The addition of Giapreza to background treatment in refractory DS in the ICU setting is cost-effective.

Usefulness and Cost-Effectiveness of Universal Echocardiographic Contrast to Detect Left Ventricular Thrombus in Patients with Heart Failure and Reduced Ejection Fraction

Contrast is a recommended but frequently unused tool in transthoracic echocardiography to improve detection of left ventricular thrombus in patients with ejection fraction (EF) ≤35%. The clinical and economic outcomes of a possible solution (i.e., universal contrast use) remain uncertain. To estimate clinical benefit, cost, and cost-effectiveness of a diagnostic strategy of universal use of contrast (vs no contrast) during echocardiography in patients with reduced EF, we created a decision analytic model using echocardiography sensitivity and specificity for left ventricular thrombus detection from a meta-analysis, as well as survival and cost estimates from published literature. Universal contrast use (vs nonuse) did not result in clinical or statistical improvement in estimated life years (8.509 vs 8.504) or quality-adjusted life years (5.620 vs 5.616). The cost of contrast was offset by reductions in subsequent health-care costs, resulting in similar total costs ($201,569 vs $201,573). In conclusion, although an intuitively attractive practice improvement strategy, universal contrast use strategy appears to offer no appreciable benefit to quality-adjusted survival or financial outcomes in patients with low EF.

Quality-Adjusted Survival With nab-Paclitaxel Versus Standard Paclitaxel in Metastatic Breast Cancer: A Q-TWiST Analysis

BackgroundIn this analysis we compared quality-adjusted survival outcomes between nab-paclitaxel (nab-P) and standard paclitaxel (Pac) using data from the nab-P phase III registration trial in metastatic breast cancer. Patients and MethodsQuality-adjusted overall survival was estimated using the quality-adjusted time without symptoms or toxicity (Q-TWiST) approach. Overall survival was partitioned into time without progression/Grade ≥ 3 adverse events (AEs) toxicity (TWiST), time with Grade ≥ 3 AE toxicity (TOX), and time after relapse (REL). Q-TWiST was calculated by multiplying mean time in each health state by its assigned utility (base-case utility values: time without symptoms of disease progression or toxicity of Grade ≥ 3 adverse events [TWiST] = 1.0, TOX = 0.5, and REL = 0.5). In threshold analyses, TOX and REL varied from 0.0 to 1.0 whereas TWiST was maintained at 1.0. Comparisons were made for the intent-to-treat population and the subset of patients initiating the study drugs as second or subsequent lines (2L+) of chemotherapy (per approved nab-P indication; 2L+ subpopulation). A ≥ 15% relative Q-TWiST gain (vs. mean Pac overall survival) was considered clearly clinically important. ResultsIn the intent-to-treat population, nab-P (n = 229) versus Pac (n = 225) resulted in nonsignificant gains of 1.4 months of mean Q-TWiST (11.6 vs. 10.2 months; 95% confidence interval [CI], −0.03 to 2.8). In the 2L+ subpopulation, nab-P (n = 132) versus Pac (n = 136) resulted in a statistically significant gain of 2.2 months of mean Q-TWiST (10.5 vs. 8.4 months; 95% CI, 0.6-3.8), with a 17.1% relative Q-TWiST gain (threshold analysis range, 14.0%-19.5%, both figures significant). ConclusionIn its approved indication for metastatic breast cancer, nab-P showed a statistically significant and clearly clinically important improvement in quality-adjusted survival time versus Pac in the 2L+ subpopulation.

Cost effectiveness of focal impulse and rotor modulation guided ablation added to pulmonary vein isolation for atrial fibrillation.

Although ablation with focal impulse and rotor modulation (FIRM), as an adjunct to pulmonary vein isolation (PVI), has been shown to decrease atrial fibrillation (AF) recurrence, cost-effectiveness has not been assessed. We aimed to evaluate the cost effectiveness of FIRM-guided ablation when added to PVI in a mixed AF population. We used a Markov model to estimate the costs, quality-adjusted survival, and cost effectiveness of adding FIRM ablation to PVI. AF recurrence rates were based on 3-year data from the CONFIRM trial. Model inputs for event probabilities and utilities were obtained from literature review. Costs were based on Medicare reimbursement, wholesale acquisition costs, and literature review. Three-year total costs FIRM+PVI versus PVI alone were $27,686versus $26,924. QALYs were 2.338versus 2.316, respectively, resulting in an incremental cost-effectiveness ratio (ICER) of $34,452 per QALY gained. Most of the cost (65-81%) was related to the index ablation procedure. Lower AF recurrence generated cost offsets of $4,266, primarily due to a reduced need for medications and repeat ablation. Probabilistic sensitivity analysis demonstrated ICER below $100,000/QALY in 74% of simulations. Based on data from the CONFIRM study, the addition of FIRM to PVI does have the potential to be cost-effective due to higher quality-adjusted life years and lower follow-up costs. Value is sensitive to the incremental reduction in AF recurrence, and FIRM may have the greatest economic value in patients with greater AF symptom severity. Results from ongoing randomized trials will provide further clarity.

Quality of life in patients with advanced epithelial ovarian cancer (EOC) randomized to maintenance pazopanib or placebo after first-line chemotherapy in the AGO-OVAR 16 trial. Measuring what matters—patient-centered end points in trials of maintenance therapy

BackgroundHealth-related quality of life (HRQoL) was a secondary end point in AGO-OVAR 16, which randomized 940 patients with EOC after first-line chemotherapy to maintenance pazopanib (PZ) or placebo (P). Additional post hoc analyses were carried out to investigate additional patient-centered end points. Patients and methodsHRQoL was measured with EORTC-QLQ-C30, QLQ-OV28 and EQ-5D-3L. Pre-specified end points included mean differences in HRQoL between treatment arms. Exploratory analyses included quality-adjusted progression-free survival (QAPFS), impact of specific symptoms and progressive disease (PD) on HRQoL and time to second-line chemotherapy. The objective was to provide clinical perspective to the significant median PFS gain of 5.6months with PZ. ResultsThere were statistically significant differences between PZ and P in QLQ-C30 global health status [5.5 points; 95% confidence interval (CI), 0.7–10.4, P=0.024] from baseline to 25months, but not EQ-5D-3L (0.018 points; 95% CI−0.033 to 0.069, P=0.485). The impact of diarrhea was captured in QLQ-OV28 Abdominal/GI-Symptoms scale (8.1 points; 95% CI 3.6–12.5, P=0.001). QAPFS was 386days (95% CI 366–404days) with PZ versus 359days (95% CI 338–379days) with placebo (P=0.052). PD was associated with a decline in HRQoL (P<0.0001). Median time to second-line chemotherapy was 19.7months with PZ and 15.0months with P [hazard ratio (HR) 0.72, 95% CI 0.69–0.86, P=0.0001]. ConclusionsThere were small to no significant mean score differences in global HRQoL and EQ5D-3L between PZ and placebo, respectively, despite the increased toxicity of PZ. Exploratory end points including QAPFS, impact of specific symptoms on HRQoL during treatment and at PD help place the PFS gain with PZ in context and interpret the results. Additional patient-centered end points should be considered in trials of maintenance therapy in EOC beyond mean differences in HRQoL scores alone, to support the benefit to patients of prolongation of PFS. Clinical Trials Registration NumberNCT00866697

Addition of docetaxel to first-line long-term hormone therapy in prostate cancer (STAMPEDE): Long-term survival, quality-adjusted survival, and cost-effectiveness analysis.

162 Background: Results from large randomised controlled trials have shown that adding docetaxel to standard of care (SOC) in men initiating hormone therapy for prostate cancer prolongs survival for those with metastatic disease and prolongs time to treatment failure for those without metastatic disease. We report on the impact of docetaxel on health related quality of life (HRQoL), resource use and cost-effectiveness for men treated in the STAMPEDE trial. Methods: Health outcomes and costs in the UK NHS were modelled using EuroQol (EQ-5D)and resource use data collected within the STAMPEDE trial (STAMPEDE enrolled men advanced prostate cancer starting first line hormone therapy. SOC was hormone therapy for ≥2 years and radiotherapy in some patients. Docetaxel (75 mg/m2) was administered alongside SOC for six 3-weekly cycles with prednisolone 10 mg daily. Lifetime predictions of costs, changes in predicted survival duration, quality adjusted life years (QALYs), and incremental cost effectiveness ratios (ICERs) were calculated. Results: Compared to patients allocated SOC, docetaxel was estimated to extend predicted survival by an average of 0.89 years for M1 patients and 0.78 years for M0 patients. Docetaxel was estimated to extend discounted QALYs by 0.51 years in M1 patients and 0.39 years in M0 patients. QALY gains in M0 patients were driven by the beneficial effect of delayed and reduced relapse. Docetaxel was cost-effective both in M1 patients (ICER = £5,514/QALY vs. SOC) and M0 patients (higher QALYs, lower costs vs. SOC). The probabilistic sensitivity analysis indicated a very high probability ( &gt; 99%) that docetaxel is cost-effective in both M0 and M1 patients. Docetaxel remained cost effective in M0 patients even when no survival advantage was assumed due to reductions and delays in relapse. Conclusions: Docetaxel improves overall HRQoL, delays time to, and reduces the need for, subsequent therapy, and is cost-effective, amongst patients with both non-metastatic and metastatic disease. Clinicians should consider whether the evidence is now sufficiently compelling to support docetaxel use in non-metastatic patients. Clinical trial information: ISRCTN78818544.

Identifying high surgical risk in muscle-invasive bladder cancer (MIBC) patients undergoing radical cystectomy (RC).

460 Background: Although RC is the standard treatment for MIBC, it is associated with non-negligible morbidity and mortality. Given the advanced age and prevalence of comorbidities in MIBC patients, many are suboptimal RC candidates. We sought to develop a prediction rule for determining high surgical risk using routinely available pre-surgical variables. Methods: We identified N=8,634 patients with MIBC (cT2-T4aN0M0) who underwent RC, without perioperative chemotherapy, within the National Cancer Database (2003-2012). Using multi-state modeling, we calculated time spent in 3 health states: hospitalized, discharged and death over 90 days post-RC. Predictors were selected in a stepwise manner. Cross validation was performed leaving one of 6 geographic regions out to assess model performance. Time spent in each state was weighted by utility (0=death, 1=full health) to determine 90d quality-adjusted survival (QAS) as a composite of morbidity and mortality. Results: Median age: 69y (IQR 62-78), mean length of stay: 10±12d, and 90d mortality: 654/8,634 (7.6%). Increasing age, cT stage, Charlson comorbidity index (CCI) and lower hospital RC volume were associated with greater 90d mortality (Table). C-statistics of 0.57-0.73 and calibration slopes of 0.54-1.37 (1=perfect) were sufficient across the regions. Our model predicted 25% of patients had a 90d mortality &gt;10%; observed 90d mortality in this group was 14.0% (95% CI 12.5-15.5). Mean QAS was 63d (range 43-68). Conclusions: We developed a multi-state model to identify high post-RC risk that may ultimately help to identify patients for ‘prehabilitation’ strategies and/or inform standard definitions of ‘cystectomy ineligibility’ for clinical trials. [Table: see text]

Abstract OT1-03-05: The DETECT V-Study – Comparison of dual HER2-targeted therapy with trastuzumab plus pertuzumab in combination with chemo- or endocrine therapy in addition with CDK4/6 inhibition in patients with HER2-positive and hormone-receptor positive metastatic breast cancer

Abstract Background:Metastatic breast cancer (MBC) is usually an incurable disease and maintenance of quality of life (QoL) is one of the main aims of therapy. In patients with HER2-positive MBC taxane-based chemotherapy in combination with dual HER2 targeted therapy with trastuzumab and pertuzumab, has shown significantly increased progression free survival and overall survival. Adverse events are well-known side effects of any cytostatic treatment and can seriously impact the patients' QoL. The synergistic combination of dual HER2-targeted therapy with trastuzumab and pertuzumab plus endocrine therapy might offer a better treatment option for these patients. Preclinical data and first clinical trial results suggest an additional benefit when a CDK4/6 inhibitor is added to the combination of endocrine therapy and anti HER2 treatment. DETECT V is a randomized phase III study comparing the safety and efficacy of trastuzumab plus pertuzumab in combination with either endocrine therapy or chemotherapy. In both treatment arms the CDK4/6 inhibitor ribociclib will be added. Trial design and eligibility criteria: Patients are 1:1 randomized to receive dual HER2-targeted therapy with trastuzumab and pertuzumab combined with endocrine therapy and ribociclib or to chemotherapy with trastuzumab and pertuzumab followed by maintenance therapy with trastuzumab, pertuzumab, endocrine therapy and ribociclib when chemotherapy has stopped. The sample size calculations are based on the assumption that the probability of having an adverse event as defined by the modified adverse event score for patients with HER2 positive metastatic breast cancer in the chemotherapy arm is 86.3%. Based on this assumption, a minimum of 121 patients per treatment arm is required to detect a 25% decreased risk of having an adverse event as defined by the modified adverse event score (i.e. a relative risk ratio of 0.75) for patients treated with dual HER2-targeted plus endocrine therapy and ribociclib as compared to patients treated with dual HER2-targeted plus chemotherapy with the combination of endocrine therapy and ribociclib as maintenance treatment (90% power, two-sided test, α = 0.05). Specific aims: The primary objective of this study is to assess the tolerability of both treatment strategies, as assessed by the occurrence of AEs during the treatment period. Modified adverse event score was developed in order to better reflect the clinical, physiological and psychological impact of AEs on patients' QoL. Key secondary endpoint, besides the efficacy endpoints progression free survival (PFS) and overall survival, is to compare quality-adjusted survival (QAS), as measured using the quality-adjusted time without symptoms and toxicity (Q-TWiST) method, between both treatment arms. The DETECT V trial comes along with a comprehensive translational program focusing on detection and phenotyping of circulating tumor cell (CTC)-and the assessment of marker expression on CTCs in order to calculate an endocrine responsiveness score. Citation Format: Romashova T, Polasik A, Friedl TWP, Rack B, Tzschaschel M, Fasching PA, Taran F-A, Hartkopf A, Schneeweiss A, Mueller V, Bahriye A, Pantel K, Meier-Stiegen F, Wimberger P, Janni W, Fehm T, Huober J. The DETECT V-Study – Comparison of dual HER2-targeted therapy with trastuzumab plus pertuzumab in combination with chemo- or endocrine therapy in addition with CDK4/6 inhibition in patients with HER2-positive and hormone-receptor positive metastatic breast cancer [abstract]. In: Proceedings of the 2017 San Antonio Breast Cancer Symposium; 2017 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2018;78(4 Suppl):Abstract nr OT1-03-05.

Cost-Effectiveness of Ivabradine in the Treatment of Chronic Heart Failure

In the Systolic Heart failure treatment with the If inhibitor Trial (SHIFT) randomised placebo-controlled trial, ivabradine was shown to reduce hospital admissions for worsening heart failure (HF) and deaths due to HF in patients with symptomatic systolic HF and an elevated resting heart rate (HR). This analysis evaluates the cost effectiveness of adding ivabradine to optimal standard HF treatment in patients with a HR≥77 bpm. A Markov model was developed to assess the impact of ivabradine on mean survival and quality of life over a patient's lifetime (10 years). The hospitalisation and death rates were calculated using patient-level data from SHIFT. The reduction in quality of life due to HF hospitalisations was estimated directly from EQ-5D data collected in SHIFT. Australian costs were applied to the resource use from SHIFT. The modelled mean increase in survival with ivabradine was 0.115 years. The mean increase in quality-adjusted survival was 0.108 years. The average cost of ivabradine was A$2,957 and the cost savings associated with a reduction in HF hospitalisations was A$1,344. The cost per quality adjusted life year gained (QALYG) was A$14,905. The conservative approach to the modelled evaluation, as well as results of the sensitivity analysis, demonstrates that ivabradine is likely to be cost-effective in this indication. The conservative approach to the modelled evaluation, as well as results of the sensitivity analysis, demonstrates that ivabradine is a cost-effective treatment in the Australian setting for HF patients with a HR≥77 bpm on optimal standard therapy with a cost per QALYG similar or lower than that for other publicly funded treatments.

Comparative quality-adjusted survival analysis between radiation therapy alone and radiation with androgen deprivation therapy in patients with locally advanced prostate cancer: a secondary analysis of Radiation Therapy Oncology Group 85-31 with novel decision analysis methods.

BackgroundAndrogen deprivation therapy in addition to radiation therapy (RT + ADT) has shown benefits in local control and progression-free survival compared with RT alone for patients with locally advanced prostate cancer in Radiation Therapy Oncology Group 85-31. However, the survival gain may be diluted with increased toxicity of ADT. The aim of the study is to compare quality-adjusted life years (QALYs) values between two groups.MethodsWe developed “quality-adjusted survival analysis using duration” (QASAD) and “quality-adjusted survival analysis using probability” (QASAP) to estimate the quality-adjusted survival time. The QASAD uses the median duration in each health state to weight the utilities, whereas the QASAP uses the proportional probability of being in each state for weighting. The survival and complication rates were reconstructed based on published Kaplan–Meier survival curves, and the utility values for states were obtained from the previous literature.ResultsQALYs values for RT + ADT were generally higher than those for RT. The QASAD resulted in a QALY value of 4.93 [95% bootstrapped confidence interval (CI) = 4.12–5.71] for RT and of 5.60 (95% CI = 4.30–6.48) for RT + ADT. QASAP resulted in a QALY value of 4.85 (95% CI = 4.16–5.39) for RT and 4.96 (95% CI = 3.73–5.78) for RT + ADT.ConclusionsWe showed that RT + ADT provided slightly better quality-adjusted survival outcome than RT alone. The QASAD and QASAP methods may help the decision of optimal treatment balancing between survival gain and unfavorable quality of life.

Combining Survival and Toxicity Effect Sizes from Clinical Trials: NCCTG 89-20-52 (Alliance).

Background:How can a clinician and patient incorporate survival and toxicity information into a single expression of comparative treatment benefit? Sloan et al. recently extended the ½ standard deviation concept for judging the clinical importance of findings from clinical trials to survival and tumor response endpoints. A new method using this approach to combine survival and toxicity effect sizes from clinical trials into a quality-adjusted effect size is presented.Methods:The quality-adjusted survival effect size (QASES) is calculated as survival effect size (ESS) minus the calibrated toxicity effect sizes (EST) (QASES=ESS-EST). This combined effect size can be weighted to adjust for the relative emphasis placed by the patient on survival and toxicity effects.Results:As an example, consider clinical trial NCCTG 89–20-52 which randomized patients to once-daily thoracic radiotherapy (ODTRT) versus twice-daily treatment of thoracic radiotherapy (TDRT) for the treatment of lung cancer. The ODTRT vs. TDRT arms had median survival time of 22 vs. 20 months (p=0.49) and toxicity rate of 39% vs. 54%, (p<0.05). The QASES of 0.18 standard deviations translates to a quality-adjusted survival difference of 5.7 months advantage for the ODRT arm over the TDRT treatment arm (22(16.3) months), p<0.05). Similar results are presented for the four possible case combinations of significant/non-significant survival and toxicity benefits using completed clinical trials.Conclusions:We used a novel approach to re-analyze clinical trial data to produce a single estimate for each treatment that combines survival and toxicity data. The QASES approach is an intuitive and mathematically simple yet robust approach.