United States Value Set for the Functional Assessment of Cancer Therapy-General Eight Dimensions (FACT-8D), a Cancer-Specific Preference-Based Quality of Life Instrument.

OBJECTIVES: To develop a value set reflecting the United States (US) general population's preferences for health states described by the Functional Assessment of Cancer Therapy (FACT) eight-dimensions preference-based multi-attribute utility instrument (FACT-8D), derived from the FACT-General cancer-specific health-related quality-of-life (HRQL) questionnaire. METHODS: A US online panel was quota-sampled to achieve a general population sample representative by sex, age (≥ 18 years), race and ethnicity. A discrete choice experiment (DCE) was used to value health states. The valuation task involved choosing between pairs of health states (choice-sets) described by varying levels of the FACT-8D HRQL dimensions and survival (life-years). The DCE included 100 choice-sets; each respondent was randomly allocated 16 choice-sets. Data were analysed using conditional logit regression parameterized to fit the quality-adjusted life-year framework, weighted for sociodemographic variables that were non-representative of the US general population. Preference weights were calculated as the ratio of HRQL-level coefficients to the survival coefficient. RESULTS: 2562 panel members opted in, 2462 (96%) completed at least one choice-set and 2357 (92%) completed 16 choice-sets. Pain and nausea were associated with the largest utility weights, work and sleep had more moderate utility weights, and sadness, worry and support had the smallest utility weights. Within dimensions, more severe HRQL levels were generally associated with larger weights. A preference-weighting algorithm to estimate US utilities from responses to the FACT-General questionnaire was generated. The worst health state's value was -0.33. CONCLUSIONS: This value set provides US population utilities for health states defined by the FACT-8D for use in evaluating oncology treatments.

The Functional Assessment of Cancer Therapy Scale: Development and Validation of the General Measure.

PURPOSE: We developed and validated a brief, yet sensitive, 33-item general cancer quality-of-life (QL) measure for evaluating patients receiving cancer treatment, called the Functional Assessment of Cancer Therapy (FACT) scale. METHODS AND RESULTS: The five-phase validation process involved 854 patients with cancer and 15 oncology specialists. The initial pool of 370 overlapping items for breast, lung, and colorectal cancer was generated by open-ended interview with patients experienced with the symptoms of cancer and oncology professionals. Using preselected criteria, items were reduced to a 38-item general version. Factor and scaling analyses of these 38 items on 545 patients with mixed cancer diagnoses resulted in the 28-item FACT-general (FACT-G, version 2). In addition to a total score, this version produces subscale scores for physical, functional, social, and emotional well-being, as well as satisfaction with the treatment relationship. Coefficients of reliability and validity were uniformly high. The scale's ability to discriminate patients on the basis of stage of disease, performance status rating (PSR), and hospitalization status supports its sensitivity. It has also demonstrated sensitivity to change over time. Finally, the validity of measuring separate areas, or dimensions, of QL was supported by the differential responsiveness of subscales when applied to groups known to differ along the dimensions of physical, functional, social, and emotional well-being. CONCLUSION: The FACT-G meets or exceeds all requirements for use in oncology clinical trials, including ease of administration, brevity, reliability, validity, and responsiveness to clinical change. Selecting it for a clinical trial adds the capability to assess the relative weight of various aspects of QL from the patient's perspective.

Effects of neratinib on health-related quality of life in women with HER2-positive early-stage breast cancer: longitudinal analyses from the randomized phase III ExteNET trial.

BACKGROUND: We report longitudinal health-related quality-of-life (HRQoL) data from the international, randomized, double-blind, placebo-controlled phase III ExteNET study, which demonstrated an invasive disease-free survival benefit of extended adjuvant therapy with neratinib over placebo in human epidermal growth factor receptor-2-positive early-stage breast cancer. PATIENTS AND METHODS: Women (N = 2840) with early-stage HER2-positive breast cancer who had completed trastuzumab-based adjuvant therapy were randomly assigned to neratinib 240 mg/day or placebo for 12 months. HRQoL was an exploratory end point. Patients completed the Functional Assessment of Cancer Therapy-Breast (FACT-B) and EuroQol 5-Dimensions (EQ-5D) questionnaires at baseline and months 1, 3, 6, 9, and 12. Changes from baseline were compared using analysis of covariance with no imputation for missing values. Sensitivity analyses used alternative methods. Changes in HRQoL scores were regarded as clinically meaningful if they exceeded previously reported important differences (IDs). RESULTS: Of the 2840 patients (intention-to-treat population), 2407 patients were evaluable for FACT-B (neratinib, N = 1171; placebo, N = 1236) and 2427 patients for EQ-5D (neratinib, N = 1186; placebo, N = 1241). Questionnaire completion rates exceeded 85%. Neratinib was associated with a decrease in global HRQoL scores at month 1 compared with placebo (adjusted mean differences: FACT-B total, -2.9 points; EQ-5D index, -0.02), after which between-group differences diminished at later time-points. Except for the FACT-B physical well-being (PWB) subscale at month 1; all between-group differences were less than reported IDs. The FACT-B breast cancer-specific subscale showed small improvements with neratinib at months 3-9, but all were less than IDs. Sensitivity analyses exploring missing data did not change the results. CONCLUSIONS: Extended adjuvant neratinib was associated with a transient, reversible decrease in HRQoL during the first month of treatment, possibly linked to treatment-related diarrhea. With the exception of the PWB subscale at month 1, all neratinib-related HRQoL changes did not reach clinically meaningful thresholds. ClinicalTrials.gov: NCT00878709.

Health utility scores from EQ-5D and health-related quality of life in patients with esophageal cancer: a real-world cross-sectional study.

Esophageal cancer and its treatment can cause serious morbidity/toxicity. These effects on health-related quality of life (HRQOL) can be measured using disease-specific scales such as FACT-E, generic scales such as EQ-5D-3L, or through symptoms. In a two-year cross-sectional study, we compared HRQOL across esophageal cancer patients treated in an ambulatory clinic and across multiple disease states, among patients with all stages of esophageal cancer. Consenting patients completed FACT-E, EQ-5D, a visual analog scale, and patient reported (PR)-ECOG. Symptom complexes were constructed from FACT-E domains. Responses were categorized by disease state: pre-, during, and post-treatment, surveillance, progression, and palliative chemotherapy. Spearman correlation and multivariable linear regression characterized these associations. In total, 199 patients completed 317 questionnaires. Mean FACT-E and subscale scores dropped from baseline through treatment and recovered during post-treatment surveillance (P < 0.001); EQ-5D health utility scores (HUS) displayed a similar pattern but with smaller differences (P = 0.07), and with evidence of ceiling effect. Among patients with stage II/III esophageal cancer, mean EQ-5D HUS varied across disease states (P < 0.001), along with FACT-E and subscales (P < 0.001). Among patients with advanced disease, there was no significant difference between baseline and on-treatment total scores, but improved esophageal cancer-specific scales were noted (P = 0.003). Strong correlation was observed between EQ-5D and FACT-E (R = 0.73), along with physical and functional subscales. In addition, the association between FACT-E and EQ-5D HUS was maintained in a multivariable model (P < 0.001). We interpret these results to suggest that in a real-world clinic setting, FACT-E, EQ-5D HUS, and symptoms were strongly correlated. Most HRQOL and symptom parameters suggested that patients had worse HRQOL and symptoms during curative therapy, but recovered well afterwards. In contrast, palliative chemotherapy had a neutral to positive impact on HRQOL/symptoms when compared to their baseline pre-treatment state.

Relationship between patient-reported outcomes and clinical outcomes in metastatic castration-resistant prostate cancer: post hoc analysis of COU-AA-301 and COU-AA-302.

Background: Patient-reported outcomes (PROs) are used to assess benefit-risk in drug development. The relationship between PROs and clinical outcomes is not well understood. We aim to elucidate the relationships between changes in PRO measures and clinical outcomes in metastatic castration-resistant prostate cancer (mCRPC). Patients and methods: We investigated relationships between changes in self-reported fatigue, pain, functional well-being (FWB), physical well-being (PWB) and prostate cancer-specific symptoms with overall survival (OS) and radiographic progression-free survival (rPFS) after 6 and 12 months of treatment in COU-AA-301 (N = 1195) or COU-AA-302 (N = 1088). Eligible COU-AA-301 patients had progressed after docetaxel and had Eastern Cooperative Oncology Group performance status (ECOG PS) ≤ 2. Eligible COU-AA-302 patients had no prior chemotherapy and ECOG PS 0 or 1. Patients were treated with abiraterone acetate (1000 mg/day) plus prednisone (10 mg/day) or prednisone alone daily. Association between self-reported fatigue, pain and functional status, and OS and/or rPFS, using pooled data regardless of treatment, was assessed. Cox proportional hazard regression modeled time to death or radiographic progression. Results: In COU-AA-301 patients, PRO improvements were associated with longer OS and longer time to radiographic progression versus worsening or stable PROs (P < 0.0001). In multivariate models, all except pain intensity remained associated with OS. Pain intensity, PWB and FWB improvements remained associated with rPFS. In COU-AA-302 patients, worsening PROs were associated with higher likelihood of radiographic progression (P ≤ 0.025) compared with improved or stable PROs. In multivariate models, worsening PWB remained associated with worse rPFS. The 12-month analysis confirmed the 6-month results. Conclusions: PROs are significantly associated with clinically relevant time-to-event efficacy outcomes in clinical trials and may complement and help predict traditional clinical practice methods for monitoring patients for disease progression.

Quality of life is significantly associated with survival in women with advanced epithelial ovarian cancer: An ancillary data analysis of the NRG Oncology/Gynecologic Oncology Group (GOG-0218) study.

OBJECTIVE: Evaluate association between baseline quality of life (QOL) and changes in QOL measured by FACT-O TOI with progression-free disease (PFS) and overall survival (OS) in advanced epithelial ovarian cancer (EOC). METHODS: Patients enrolled in GOG-0218 with completed FACT-O TOI assessments at baseline and at least one follow-up assessment were eligible. Baseline FACT-O TOI scores were sorted by quartiles (Q1-4) and outcomes compared between Q1 and Q2-4 with log-rank statistic and multivariate Cox regression adjusting for age, stage, post-surgical residual disease size, and performance status (PS). Trends in FACT-O TOI scores from baseline to the latest follow-up assessment were evaluated for impact on intragroup (Q1 or Q2-4) outcome by log-rank analysis. RESULTS: Of 1152 eligible patients, 283 formed Q1 and 869 formed Q2-4. Mean baseline FACT-O TOI scores were 47.5 for Q1 vs. 74.7 for Q2-4 (P<0.001). Q1 compared to Q2-4 had worse median OS (37.5 vs. 45.6months, P=0.001) and worse median PFS (12.5 vs. 13.1months, P=0.096). Q2-4 patients had decreased risks of disease progression (HR 0.974, 95% CI 0.953-0.995, P=0.018), and death (HR 0.963, 95% CI 0.939-0.987, P=0.003) for each five-point increase in baseline FACT-O TOI. Improving versus worsening trends in FACT-O TOI scores were associated with longer median PFS (Q1: 12.7 vs. 8.6months, P=0.001; Q2-4: 16.7 vs. 11.1months, P<0.001) and median OS (Q1: 40.8 vs. 16months, P<0.001; Q2-4: 54.4 vs. 33.6months, P<0.001). CONCLUSIONS: Baseline FACT-O TOI scores were independently prognostic of PFS and OS while improving compared to worsening QOL was associated with significantly better PFS and OS in women with EOC.

Transforming the Perioperative Treatment Paradigm in Non-Metastatic RCC-A Possible Path Forward.

In 2017, there is no adjuvant systemic therapy proven to increase overall survival in non-metastatic renal cell carcinoma (RCC). The anti-PD-1 antibody nivolumab improves overall survival in metastatic treatment refractory RCC and is generally tolerable. Mouse solid tumor models have revealed a benefit with a short course of neoadjuvant PD-1 blockade compared to adjuvant therapy. Two ongoing phase 2 studies of perioperative nivolumab in RCC patients have shown preliminary feasibility and safety with no surgical delays or complications. The recently opened PROSPER RCC trial (A Phase 3 RandOmized Study Comparing PERioperative Nivolumab vs. Observation in Patients with Localized Renal Cell Carcinoma Undergoing Nephrectomy; EA8143) will examine if the addition of perioperative nivolumab to radical or partial nephrectomy can improve clinical outcomes in patients with high risk localized and locally advanced RCC. With the goal of increasing cure and recurrence-free survival (RFS) rates in non-metastatic RCC, we are executing a three-pronged, multidisciplinary approach of presurgical priming with nivolumab followed by resection and adjuvant PD-1 blockade. We plan to enroll 766 patients with clinical stage ≥T2 or node positive M0 RCC of any histology in this global, randomized, unblinded, phase 3 National Clinical Trials Network study. The investigational arm will receive two doses of nivolumab 240 mg IV prior to surgery followed by adjuvant nivolumab for 9 months. The control arm will undergo the current standard of care: surgical resection followed by observation. Patients are stratified by clinical T stage, node positivity, and histology. The trial is powered to detect a 14.4% absolute benefit in the primary endpoint of RFS from the ASSURE historical control of 55.8% to 70.2% at 5 years (HR = 0.70). The study is also powered to detect a significant overall survival benefit (HR 0.67). Key safety, feasibility, and quality of life endpoints are incorporated. PROSPER RCC exemplifies team science with a host of planned correlative work to investigate the impact of the baseline immune milieu and changes after neoadjuvant priming on clinical outcomes.

QLU-C10D: a health state classification system for a multi-attribute utility measure based on the EORTC QLQ-C30.

PURPOSE: To derive a health state classification system (HSCS) from the cancer-specific quality of life questionnaire, the EORTC QLQ-C30, as the basis for a multi-attribute utility instrument. METHODS: The conceptual model for the HSCS was based on the established domain structure of the QLQ-C30. Several criteria were considered to select a subset of dimensions and items for the HSCS. Expert opinion and patient input informed a priori selection of key dimensions. Psychometric criteria were assessed via secondary analysis of a pooled dataset comprising HRQOL and clinical data from 2616 patients from eight countries and a range of primary cancer sites, disease stages, and treatments. We used confirmatory factor analysis (CFA) to assess the conceptual model's robustness and generalisability. We assessed item floor effects (>75 % observations at lowest score), disordered item response thresholds, coverage of the latent variable and differential item function using Rasch analysis. We calculated effect sizes for known group comparisons based on disease stage and responsiveness to change. Seventy-nine cancer patients assessed the relative importance of items within dimensions. RESULTS: CFA supported the conceptual model and its generalisability across primary cancer sites. After considering all criteria, 12 items were selected representing 10 dimensions: physical functioning (mobility), role functioning, social functioning, emotional functioning, pain, fatigue, sleep, appetite, nausea, bowel problems. CONCLUSIONS: The HSCS created from QLQ-C30 items is known as the EORTC Quality of Life Utility Measure-Core 10 dimensions (QLU-C10D). The next phase of the QLU-C10D's development involves valuation studies, currently planned or being conducted across the globe.

Using a discrete choice experiment to value the QLU-C10D: feasibility and sensitivity to presentation format.

PURPOSE: To assess the feasibility of using a discrete choice experiment (DCE) to value health states within the QLU-C10D, a utility instrument derived from the QLQ-C30, and to assess clarity, difficulty, and respondent preference between two presentation formats. METHODS: We ran a DCE valuation task in an online panel (N = 430). Respondents answered 16 choice pairs; in half of these, differences between dimensions were highlighted, and in the remainder, common dimensions were described in text and differing attributes were tabulated. To simplify the cognitive task, only four of the QLU-C10D's ten dimensions differed per choice set. We assessed difficulty and clarity of the valuation task with Likert-type scales, and respondents were asked which format they preferred. We analysed the DCE data by format with a conditional logit model and used Chi-squared tests to compare other responses by format. Semi-structured telephone interviews (N = 8) explored respondents' cognitive approaches to the valuation task. RESULTS: Four hundred and forty-nine individuals were recruited, 430 completed at least one choice set, and 422/449 (94 %) completed all 16 choice sets. Interviews revealed that respondents found ten domains difficult but manageable, many adopting simplifying heuristics. Results for clarity and difficulty were identical between formats, but the "highlight" format was preferred by 68 % of respondents. Conditional logit parameter estimates were monotonic within domains, suggesting respondents were able to complete the DCE sensibly, yielding valid results. CONCLUSION: A DCE valuation task in which only four of the QLU-C10D's ten dimensions differed in any choice set is feasible for deriving utility weights for the QLU-C10D.

A randomized, double-blind, phase II, exploratory trial evaluating the palliative benefit of either continuing pamidronate or switching to zoledronic acid in patients with high-risk bone metastases from breast cancer.

Previous studies suggest switching from pamidronate to a more potent bone-targeted agent is associated with biomarker and palliative response in breast cancer patients with bone metastases. Until now, this has not been addressed in a double-blind, randomized trial. Breast cancer patients with high-risk bone metastases, despite >3 months of pamidronate, were randomized to either continue pamidronate or switch to zoledronic acid every 4 weeks for 12 weeks. Primary outcome was the proportion of patients achieving a fall in serum C-telopeptide (sCTx) at 12 weeks. Secondary outcomes included difference in mean sCTx, pain scores, quality of life, toxicity, and skeletal-related events (SREs). Seventy-three patients entered the study; median age 61 years (range 37-87). Proportion of patients achieving a fall in sCTx over the 12-week evaluation period was 26/32 (81 %) with zoledronic acid and 18/29 (62 %) with pamidronate (p = 0.095). Mean decrease in sCTx (mean difference between groups = 50 ng/L, 95 % CI 18-84; p = 0.003) was significantly greater in patients who received zoledronic acid. Quality of life, pain scores, toxicity, and frequency of new SREs were comparable between the two arms. While a switch from pamidronate to zoledronic acid resulted in reduction in mean sCTx, there were no significant differences between the arms for proportion of patients achieving a reduction in sCTx, quality of life, pain scores, toxicity or SREs. Given the lack of palliative improvement, the current data do not support a switching strategy.

Impact of enzalutamide on quality of life in men with metastatic castration-resistant prostate cancer after chemotherapy: additional analyses from the AFFIRM randomized clinical trial.

BACKGROUND: To present longitudinal changes in Functional Assessment of Cancer Therapy-Prostate (FACT-P) scores during 25-week treatment with enzalutamide or placebo in men with progressive metastatic castration-resistant prostate cancer (mCRPC) after chemotherapy in the AFFIRM trial. PATIENTS AND METHODS: Patients were randomly assigned to enzalutamide 160 mg/day or placebo. FACT-P was completed before randomization, at weeks 13, 17, 21, and 25, and every 12 weeks thereafter while on study treatment. Longitudinal changes in FACT-P scores from baseline to 25 weeks were analyzed using a mixed effects model for repeated measures (MMRM), with a pattern mixture model (PMM) applied as secondary analysis to address non-ignorable missing data. Cumulative distribution function (CDF) plots were generated and different methodological approaches and models for handling missing data were applied. Due to the exploratory nature of the analyses, adjustments for multiple comparisons were not made. AFFIRM is registered with ClinicalTrials.gov, number NCT00974311. RESULTS: The intention-to-treat FACT-P population included 938 patients (enzalutamide, n = 674; placebo n = 264) with evaluable FACT-P assessments at baseline and ≥1 post-baseline assessment. After 25 weeks, the mean FACT-P total score decreased by 1.52 points with enzalutamide compared with 13.73 points with placebo (P < 0.001). In addition, significant treatment differences at week 25 favoring enzalutamide were evident for all FACT-P subscales and indices, whether analyzed by MMRM or PMM. CDF plots revealed differences favoring enzalutamide compared with placebo across the full range of possible response levels for FACT-P total and all disease- and symptom-specific subscales/indices. CONCLUSION: In men with progressive mCRPC after docetaxel-based chemotherapy, enzalutamide is superior to placebo in health-related quality-of-life outcomes, regardless of analysis model or threshold selected for meaningful response. CLINICAL TRIAL NUMBER: NCT00974311.

Patient-reported outcomes for axitinib vs sorafenib in metastatic renal cell carcinoma: phase III (AXIS) trial.

BACKGROUND: Axitinib demonstrated greater progression-free survival vs sorafenib in a phase III study of previously treated patients with metastatic renal cell carcinoma. Here, we report patient-reported kidney-specific symptoms and health status, measured by the Functional Assessment of Cancer Therapy (FACT) Kidney Cancer Symptom Index (FKSI) and the European Quality of Life self-report questionnaire (EQ-5D). METHODS: In all, 723 patients received axitinib (starting dose 5 mg twice daily (b.i.d.)) or sorafenib (400 mg b.i.d.). The FKSI-15, including the disease-related symptoms (FKSI-DRS) subscale, was administered on day 1 before dosing, every 4 weeks and at end of treatment (EOT)/withdrawal. Statistical methods included a mixed-effects repeated-measures model. RESULTS: At baseline, patients in both arms had relatively high mean FSKI-15 and FKSI-DRS scores, comparable to the general US population. Subsequent on-treatment overall mean scores were similar between axitinib and sorafenib, and there was no substantial decline during treatment. Scores substantially worsened at EOT, mainly due to disease progression. CONCLUSION: Patient-reported outcomes were comparable for second-line axitinib and sorafenib and were maintained at relatively high levels while on treatment, but worsened at EOT. As duration of treatment was longer with axitinib than sorafenib, time to worsening of symptoms can be delayed longer with axitinib.

The FACT-G7: a rapid version of the functional assessment of cancer therapy-general (FACT-G) for monitoring symptoms and concerns in oncology practice and research.

BACKGROUND: Health-related quality-of-life (HRQOL) assessments in research and clinical oncology settings are increasingly important. HRQOL instruments need to be rapid and still maintain the ability to capture the most relevant patient issues in a valid and reliable manner. The current study develops and validates the FACT-G7, a rapid version of the Functional Assessment of Cancer Therapy-General (FACT-G). PATIENTS AND METHODS: Oncology patients with advanced cancer (N = 533) from 11 diseases sites ranked the symptoms and concerns they viewed as 'the very most important' when undergoing cancer treatment, completed the FACT-G, and additional HRQOL measures. Oncology patients' scores were referenced across a general US population sample (N = 2000). RESULTS: We selected the highest priority cancer-related symptoms and concerns endorsed by patients for inclusion in the FACT-G7. Fatigue and ability to enjoy life were ranked the most highly. The results provide preliminary support for the FACT-G7's internal consistency reliability (α = 0.74) and validity as evidenced by moderate-to-strong relationships with expected criteria. The references for the general population are summarized. CONCLUSIONS: The FACT-G7 can be used to assess top-rated symptoms and concerns for a broad spectrum of advanced cancers in clinical practice and research.

Baseline quality of life as a prognostic survival tool in patients receiving sunitinib for metastatic renal cell carcinoma.

BACKGROUND: In a randomized phase III trial of sunitinib vs interferon-alfa (IFN-α) in metastatic renal cell carcinoma (mRCC), better baseline quality of life (QoL) was predictive of longer survival. Using this dataset, we have developed a novel prognostic tool that establishes a relationship between baseline QoL scores and median survival time. METHODS: Baseline QoL was assessed using the FACT-Kidney Symptom Index-15 item (FKSI-15), its disease-related symptoms (FKSI-DRS) subscale, and the Functional Assessment of Cancer Therapy-General (FACT-G) scale. Weibull models estimated median progression-free survival (mPFS) and overall survival (mOS) as a function of baseline QoL. RESULTS: Longer PFS and OS were associated with higher baseline FKSI-15, FKSI-DRS, and FACT-G scores (P<0.05), and baseline FKSI-15 score was the best predictor of survival. For example, for a baseline FKSI-15 score of 60, the predicted mPFS was 67.9 weeks, and predicted mOS was 240.6 weeks. The magnitude of benefit was greater with sunitinib vs IFN-α for a given baseline QoL score. CONCLUSION: This novel tool indicates that baseline FKSI-15 scores were linked to mPFS and mOS in a clear and interpretable way. The results support evaluation of patient-reported QoL symptoms at baseline as a prognostic indicator of survival in clinical research and practice.

Health-related quality of life in patients with advanced renal cell carcinoma receiving pazopanib or placebo in a randomised phase III trial.

BACKGROUND: In a double-blind, randomised phase III trial of advanced renal cell carcinoma patients, pazopanib 800mg QD (n=290) versus placebo (n=145) significantly prolonged progression-free survival (hazard ratio (HR)=0.46, 95% confidence interval [CI] 0.34-0.62, p-value<0.0001), without important differences in health-related quality of life (HRQoL). This post-hoc analysis evaluated time to HRQoL deterioration and whether tumour response/stabilisation was associated with HRQoL improvement. METHODS: HRQoL was assessed using EORTC QLQ-C30 and EQ-5D. Effect of pazopanib on time to ⩾20% decline from baseline in summary scores was estimated for all patients and by prior treatment. Analyses were conducted for different HRQoL deterioration thresholds. HRQoL changes were stratified by benefit and compared: complete response (CR) or partial response (PR) versus progressive disease (PD); CR/PR versus stable disease (SD), and SD versus PD. RESULTS: There was a trend for pazopanib patients to be less likely than placebo patients to experience ⩾20% HRQoL deterioration in EORTC-QLQ-C-30 global health status/QOL scale (HR=0.77; 95% CI 0.57-1.03, not significant). Results by prior treatment and different HRQoL deterioration thresholds were similar. Patients with CR/PR and SD experienced significantly less HRQoL deterioration than those with PD (p<0.001, p=0.0024, respectively); mean differences between patients with CR/PR and PD exceeded the pre-determined minimally important difference (MID). Differences between patients with SD and PD did not exceed pre-determined MID. Results were generally consistent across treatment and EQ-5D summary scores. CONCLUSION: Results support the favourable benefit-risk profile of pazopanib and suggest patients experiencing tumour response/stabilisation also may have better HRQoL compared to those without this response.

Developing a measure of health-related quality of life for women with cervical dysplasia resulting from human papillomavirus infection.

Human papillomavirus (HPV) infection is the most common sexually transmitted infection in the USA, and has major physical and psychological consequences including fear, anxiety and stigma. To date, there is no measure of health-related quality of life specifically designed to assess symptoms and functioning for people with cervical dysplasia resulting from HPV infection. In the present study, we set out to develop a disease-specific measure of health-related quality of life among women with low-grade cervical dysplasia. We conducted literature reviews, open-ended interviews with patients, clinician surveys and cognitive interviews which guided item development. The result is a preliminary 36-item measure, the Functional Assessment of Chronic Illness Therapy-Cervical Dysplasia (FACIT-CD), which sets out to assess the physical and psychological health-related quality-of-life aspects of cervical dysplasia and will be validated in an upcoming study.

Health-related quality of life in patients with metastatic renal cell carcinoma treated with sunitinib vs interferon-alpha in a phase III trial: final results and geographical analysis.

BACKGROUND: In a randomised phase III trial, sunitinib significantly improved efficacy over interferon-alpha (IFN-alpha) as first-line therapy for metastatic renal cell carcinoma (mRCC). We report the final health-related quality of life (HRQoL) results. METHODS: Patients (n=750) received oral sunitinib 50 mg per day in 6-week cycles (4 weeks on, 2 weeks off treatment) or subcutaneous IFN-alpha 9 million units three times weekly. Health-related quality of life was assessed with nine end points: the Functional Assessment of Cancer Therapy-General and its four subscales, FACT-Kidney Symptom Index (FKSI-15) and its Disease-Related Symptoms subscale (FKSI-DRS), and EQ-5D questionnaire's EQ-5D Index and visual analogue scale. Data were analysed using mixed-effects model (MM), supplemented with pattern-mixture models (PMM), for the total sample and the US and European Union (EU) subgroups. RESULTS: Patients receiving sunitinib reported better scores in the primary end point, FKSI-DRS, across all patient populations (P<0.05), and in nine, five, and six end points in the total sample, in the US and EU groups respectively (P<0.05). There were no significant differences between the US and EU groups for all end points with the exception of the FKSI item 'I am bothered by side effects of treatment' (P=0.02). In general, MM and PMM results were similar. CONCLUSION: Patients treated with sunitinib in this study had improved HRQoL, compared with patients treated with IFN-alpha. Treatment differences within the US cohort did not differ from those within the EU cohort.

Validation and reduction of FACT/GOG-Ntx subscale for platinum/paclitaxel-induced neurologic symptoms: a gynecologic oncology group study.

The FACT/GOG (Gynecologic Oncology Group) Neurotoxicity (Ntx) subscale for assessing platinum/paclitaxel-induced neurologic symptoms was evaluated. The 11-item questionnaire was administered to patients with advanced endometrial cancer treated with doxorubicin/cisplatin (AP) or doxorubicin/cisplatin/paclitaxel (TAP) prior to 1-7 cycles of treatment in GOG 177. The subscale was evaluated in 134 patients in the TAP group for internal reliability, construct validity, criteria validity, sensitivity to treatment differences, and change over time. Cronbach coefficients for internal consistency prior to cycles 1-7 were 0.85, 0.80, 0.84, 0.82, 0.82, 0.85, and 0.84, respectively. The area under the receiver operating characteristic curve was 0.81 for the Ntx score prior to cycle 3. The TAP arm Ntx scores increased significantly from 3.67 at baseline to 8.13 prior to cycle 7; these were higher than the AP arm Ntx scores, which increased from 3.54 at baseline to 4.72 prior to cycle 7. The four sensory items accounted for 80% of treatment differences and 63% of longitudinal changes in the observed subscale score. The 11-item Ntx subscale reliably and validly assesses platinum/paclitaxel-induced peripheral neuropathy. A reduced four-item version is an efficient alternative in measuring this toxicity in clinical trials without compromising its performance.

Adalimumab plus methotrexate or standard therapy is more effective than methotrexate or standard therapies alone in the treatment of fatigue in patients with active, inadequately treated rheumatoid arthritis.

OBJECTIVES: Fatigue is an important systemic symptom of rheumatoid arthritis (RA) but has rarely been evaluated consistently after initiation of treatment in RA patients. This study examined the effects of adalimumab (HUMIRA, Abbott Laboratories, Abbott Park, IL, USA), a fully human, anti-tumor necrosis factor (anti-TNF) monoclonal antibody, on reducing fatigue in patients with RA. METHODS: A total of 1526 patients with RA were enrolled in 3 randomized, placebo-controlled clinical trials of adalimumab versus placebo plus methotrexate (MTX) or placebo plus standard antirheumatic therapies. Fatigue was assessed with the Functional Assessment of Chronic Illness Therapy (FACIT) fatigue scale questionnaire (which has been validated in RA) at baseline, mid-study, and at the end of the study. Logistic regression models were constructed using baseline demographic variables to test for treatment effect. In addition, sensitivity analyses were performed to determine the robustness of the data. RESULTS: At baseline in the 3 trials, patients' fatigue ranged from 27.9-29.7, representing considerable fatigue on the FACIT fatigue scale. Fatigue was significantly and consistently reduced in adalimumab-treated patients in the 3 clinical trials. Relative to placebo plus MTX, the adalimumab 40-mg-every-other-week dosage group reported statistically significantly less fatigue at all time points post-baseline. Improvements between adalimumab and placebo ranged from 3-7 points across all 3 trials, with a 3-4-point change representing a minimum clinically important difference. CONCLUSION: Adalimumab treatment was shown to significantly reduce fatigue in patients with moderate to severe RA. Changes in fatigue in all 3 trials were found to be clinically important.