Matching-adjusted indirect comparison of isatuximab plus carfilzomib and dexamethasone with daratumumab plus lenalidomide and dexamethasone in relapsed multiple myeloma.

BACKGOUND: Lenalidomide-based regimens are commonly used for early relapse in patients with relapsed and/or refractory multiple myeloma (RRMM) receiving at least one prior line of therapy. In the absence of head-to-head comparison, matching-adjusted indirect comparison (MAIC) was conducted to demonstrate efficacy and safety of isatuximab+carfilzomib+dexamethasone (Isa-Kd) versus daratumumab + lenalidomide + dexamethasone (Dara-Rd) in RRMM. METHODS: Patient-level data from IKEMA trial (Isa-Kd, n = 179) were matched to aggregate data from POLLUX (Dara-Rd, n = 286). Hazard ratios (HR) and 95% confidence intervals (CI) for progression-free survival (PFS) and overall survival (OS) were generated by weighted Cox proportional hazard models. Odds ratios (OR), 95% CI, and p-value were calculated for ≥very good partial response (≥VGPR) and treatment-emergent adverse events (TEAEs). RESULTS: After matching, no significant differences were observed between Isa-Kd and Dara-Rd in baseline characteristics except for patients with >3 prior lines (0.0% vs. 4.9%). Isa-Kd showed significantly better PFS (HR [95% CI]: 0.46 [0.24-0.86]; p = 0.0155), statistically non-significant improvement favoring Isa-Kd in OS (0.47 [0.20-1.09]; 0.0798), and ≥VGPR (OR [95% CI]: 1.53 [0.89-2.64]; p = 0.1252) than Dara-Rd. Odds of occurrence were significantly lower for some all-grade and grade 3/4 TEAEs with Isa-Kd than Dara-Rd. CONCLUSION: These results support Isa-Kd as an efficacious treatment for early relapse in non-lenalidomide refractory patients.

The cost-effectiveness of pegaspargase versus native asparaginase for first-line treatment of acute lymphoblastic leukaemia: a UK-based cost-utility analysis.

BACKGROUND: L-asparaginase is a key component of treatment for patients with acute lymphoblastic leukaemia (ALL) in the UK. Commonly used forms of asparaginase are native E. coli-derived asparaginase (native asparaginase) and pegaspargase in first-line combination therapy, and native Erwinia chrysanthemi-derived asparaginase (Erwinia asparaginase) as second-line treatment. The objective of this study was to evaluate the cost-effectiveness of pegaspargase versus native asparaginase in first-line combination therapy for patients with newly diagnosed ALL. A combined decision tree and health-state transition Markov cost-effectiveness model was developed to assess the relative costs and health outcomes of pegaspargase versus native asparaginase in the UK setting. RESULTS: In base case analyses, first-line pegaspargase (followed by Erwinia asparaginase in cases of hypersensitivity) dominated first-line native asparaginase followed by Erwinia asparaginase; i.e. resulted in lower costs and more quality-adjusted life year gain. The favourable hypersensitivity rates and administration profile of pegaspargase led to lifetime cost savings of £4741 versus native asparaginase. Pegaspargase remained cost-effective versus all treatment strategies in all scenario analyses, including use of the 2500 IU/m2 dose, recommended for patients ≤21 years of age. CONCLUSIONS: Pegaspargase, as part of multi-drug chemotherapy, is a cost-effective option for the treatment of newly diagnosed ALL. Based on this study, The National Institute for Health and Care Excellence Technology Appraisal Committee concluded that it could recommend pegaspargase as a cost-effective use of National Health Service resources in England & Wales for treating ALL in children, young people and adults with untreated, newly diagnosed disease. TRIAL REGISTRATION: UKALL 2011, EudraCT number 2010-020924-22; UKALL 2003, EudraCT number 2007-004013-34; UKALL14, EudraCT number 2009-012717-22.

Effectiveness of Everolimus Versus Endocrine Monotherapy or Chemotherapy Among HR+/HER2- mBC Patients With Multiple Metastatic Sites.

PURPOSE: This review compared the real-world effectiveness of everolimus-based therapy versus endocrine monotherapy or chemotherapy in postmenopausal hormone receptor positive (HR+)/ human epidermal growth factor receptor 2-negative (HER2-) metastatic breast cancer (mBC) patients with multiple metastatic sites. METHODS: This retrospective chart review examined a nationwide sample of postmenopausal HR+/HER2- mBC women with ≥2 non-lymph-node metastatic sites. Patients must have initiated everolimus-based therapy (monotherapy or combination therapy including everolimus), endocrine monotherapy (any endocrine agent), or chemotherapy (monotherapy or combination with another chemotherapeutic or endocrine agent) for mBC between July 1, 2012 and August 15, 2013 after nonsteroidal aromatase inhibitor failure. Progression-free survival and time on treatment were compared using Kaplan-Meier analysis and Cox proportional hazard models, adjusting for line of therapy and baseline characteristics. FINDINGS: One hundred patients received everolimus-based therapy, 79 received endocrine monotherapy, and 86 received chemotherapy. Everolimus-based therapy was associated with significantly longer progression-free survival and time on treatment than endocrine monotherapy and chemotherapy. IMPLICATIONS: Among HR+/HER2- mBC patients with multiple metastatic sites, everolimus-based therapy was associated with better real-world effectiveness than endocrine monotherapy or chemotherapy.

Physician experiences and preferences in the treatment of HR+/HER2- metastatic breast cancer in the United States: a physician survey.

Sequential endocrine therapy (ET) is recommended for postmenopausal women with hormone receptor-positive (HR+)/human epidermal growth factor receptor 2-negative (HER2-) metastatic breast cancer (mBC) and without visceral symptoms. Chemotherapy (CT) can be considered after sequential ETs, but is associated with adverse side effects. We assessed physicians' preferences and self-reported prescribing patterns for ET and CT in the treatment of HR+/HER2- mBC at community practices in the United States. Community-based oncologists/hematologists from a nationwide online panel who treated postmenopausal women with HR+/HER2- mBC were invited to complete a survey, blinded to the identity of study sponsor. Treatment preferences were collected by treatment class of ET-based regimens versus CT and by agent for postmenopausal HR+/HER2- mBC patients after prior nonsteroidal aromatase inhibitor use in the adjuvant or mBC setting. Among 213 physicians who completed the survey, 78% were male, 71% were based in small/intermediate practices (2-9 oncologists/subspecialists), 55% had >10 years of experience, and 58% referred to the National Comprehensive Cancer Network Guidelines when treating mBC. Among first-line ETs, anastrozole was the most frequently used treatment (35%), followed by everolimus-based (EVE, 34%) and fulvestrant-based (FUL, 15%) therapy. After first-line ET, the most preferred second- and third-line treatments were ET monotherapy (48% and 39%), ET combination therapy (31% and 19%), and CT monotherapy (13% and 30%). Comparing EVE versus FUL, physicians preferred EVE in all lines but first line. Efficacy was the most important consideration for treatment choice. Physicians prescribed CT in early lines mainly because of visceral symptoms. This survey of treatment patterns for HR+/HER2- mBC in community practice suggested that after first-line ET, ET mono- or combination therapy was commonly used for the second- and third-line treatments and CT monotherapy for third- or later line treatments. CTs were used in early lines for patients with visceral symptoms.

Clinical outcomes among HR+/HER2- metastatic breast cancer patients with multiple metastatic sites: a chart review study in the US.

BACKGROUND: Hormone receptor-positive, human epidermal growth factor receptor-2-negative (HR+/HER2-) is the most common type of metastatic breast cancer (mBC). While mBC patients generally have poor prognosis with limited progression-free survival (PFS) and overall survival (OS), those with multiple metastatic sites may have even worse clinical outcomes due to multiple organ involvement. This study aimed to compare clinical outcomes including PFS, time on treatment (TOT), and OS between HR+/HER2- mBC patients with multiple metastases versus those with a single metastasis in a real-world clinical setting. METHODS: This was a retrospective chart review study of postmenopausal HR+/HER2- mBC women who had failed a non-steroidal aromatase inhibitor in the adjuvant or metastatic setting and initiated a new treatment for mBC between 07/01/2012 and 04/15/2013. Patients were classified to one of two study groups (multiple metastases or single metastasis) based on the number of non-lymph-node metastases at the initiation of the new treatment. PFS, TOT and OS were compared between the two groups using Kaplan-Meier analyses and multivariable Cox proportional hazard models adjusting for patient disease and treatment characteristics. Separate Cox models were conducted including models with an interaction term between line of therapy and study group to assess the impact of multiple metastases on clinical outcomes across different lines of therapy. RESULTS: A total of 699 patient charts were collected, including 291 patients with multiple metastases and 408 single metastasis patients. Worse performance status and a higher proportion of prior chemotherapy for mBC were observed among patients with multiple metastases. Overall, patients with multiple metastases had significantly shorter PFS [adjusted hazard ratio (HR) = 1.55, 95 % confidence interval (CI) 1.21-1.98], TOT (adjusted HR = 1.33, 95 % CI 1.05-1.67), and OS (adjusted HR = 1.77, 95 % CI 1.15-2.74) than single metastasis patients. Similar outcomes were observed in each line of therapy. CONCLUSIONS: Among HR+/HER2- mBC patients, patients with multiple metastases had significantly shorter PFS, TOT, and OS than single metastasis patients, highlighting the substantial clinical burden and unmet need for more efficacious treatments for the former group of patients.

Clinical Outcomes with First-line Endocrine Therapy or Chemotherapy in Postmenopausal HR+/HER2- Metastatic Breast Cancer.

OBJECTIVE: To describe patient profiles and clinical outcomes associated with first-line endocrine monotherapy (ET) and chemotherapy (CT) for postmenopausal HR+/HER2- metastatic breast cancer (mBC) patients. METHODS: This is a retrospective chart review of 139 postmenopausal HR+/HER2- mBC patients initiating first-line ET monotherapy or CT. Overall survival (OS) was described using Kaplan-Meier curves. Exploratory comparative proportional hazards regression was conducted. RESULTS: Patients on first-line CT had significantly more frequent liver metastases than patients on first-line ET monotherapy at baseline. The median OS was 35.5 months [95% confidence interval (CI), 22.7-41.2 months] for patients on first-line ET monotherapy and 22.2 months (95% CI, 13.6-25.9 months) for those on first-line CT (P = 0.021). Adjusting for baseline characteristics, the OS between first-line ET monotherapy and CT was not significantly different. CONCLUSIONS: Patients who were prescribed CT as first-line treatment had evidence of more advanced disease at baseline and shorter OS than those who received ET monotherapy as first-line treatment, suggesting a need for additional safe and effective treatment options for these patients.

Real-world effectiveness of everolimus-based therapy versus endocrine monotherapy and chemotherapy in patients of HR+/HER2- breast cancer with liver metastasis in the USA.

OBJECTIVE: This study investigated the comparative effectiveness of everolimus-based therapy (EVE) versus endocrine monotherapy (ET) and chemotherapy (CT) in the treatment of hormone-receptor-positive human-epidermal-growth-factor-receptor-2-negative (HR+/HER2-) metastatic breast cancer (mBC) patients with liver metastasis. METHODS: Medical charts of patients treated by community oncologists were examined. Eligible patients included postmenopausal women with HR+/HER2- mBC with liver metastasis who received EVE, ET or CT between 1 July 2012 and 15 April 2013 after non-steroidal aromatase inhibitor use. Time on treatment (TOT) and progression-free survival (PFS) were compared between EVE and ET or CT using Kaplan-Meier analyses and Cox proportional hazards models. RESULTS: Among the 202 patients in the study, 82 received EVE, 49 ET, and 71 CT. After adjusting for baseline characteristics, EVE was associated with significantly longer TOT than ET (hazard ratio [HR]: 0.49; 95% CI: 0.28 - 0.86) or CT (HR: 0.35; 95% CI: 0.22 - 0.55), and significantly longer PFS than ET (HR: 0.48; 95% CI: 0.27 - 0.87). PFS was not significantly different with EVE versus CT (HR: 0.76; 95% CI: 0.44 - 1.32). CONCLUSIONS: EVE had significantly longer TOT and PFS than ET and longer TOT than CT among postmenopausal HR+/HER2- mBC patients with liver metastasis.

Real-world effectiveness of everolimus-based therapy versus fulvestrant monotherapy in HR(+)/HER2(-) metastatic breast cancer.

AIMS: Assessing real-world effectiveness of everolimus-based therapy (EVE) versus fulvestrant monotherapy (FUL) among postmenopausal women with hormone receptor-positive (HR(+))/HER2(-) metastatic breast cancer (mBC) after progression on nonsteroidal aromatase inhibitor (NSAI). DATA & METHODS: Medical charts of community-based patients who received EVE or FUL for mBC after NSAI were examined. Progression-free survival (PFS), time on treatment and time to chemotherapy were compared using Kaplan-Meier curves and Cox proportional hazards models adjusting for line of therapy and patient characteristics. RESULTS & CONCLUSION: 192 patients received EVE and 156 FUL. After adjusting for patient characteristics, EVE was associated with significantly longer PFS than FUL (hazard ratio: 0.71; p = 0.045). EVE was associated with better PFS than FUL among NSAI-refractory postmenopausal HR(+)/HER2(-) mBC patients.

Everolimus use and associated factors among post-menopausal women with hormonal receptor positive/human epidermal growth factor receptor 2 negative metastatic breast cancer.

BACKGROUND: Everolimus has been shown to be an effective HR+/HER2- mBC treatment in both clinical trials and real-world practice. The current study aims at understanding factors associated with everolimus use and how it is used in the real world. METHODS: A retrospective chart review was conducted among postmenopausal HR+/HER2- mBC women who received everolimus, endocrine therapy (ET), or chemotherapy (CT) for mBC between 1 July 2012 and 15 April 2013 after an NSAI failure. Factors associated with everolimus use versus ET or CT were identified using multivariable logistic regressions. Reasons for prescribing everolimus and everolimus treatment patterns were described. RESULTS: Liver metastasis and high tumor volume were associated with a higher likelihood of everolimus use versus ET (OR = 1.67, OR = 1.62) but a lower likelihood of everolimus use versus CT (OR = 0.43, OR = 0.30). Medicare-only insurance (OR = 0.30) as well as ECOG ≥2 (OR = 3.72) and prior CT in mBC (OR = 2.76) were associated with a lower and higher likelihood of everolimus use versus CT, respectively. The top reason for prescribing everolimus was efficacy (69-85%). About 15% and 29% of everolimus users in second line and third line or above received prior CT for mBC. Exemestane was the most common concomitant therapy with everolimus (56-87%). The majority of patients initiated everolimus at the labeled dose of 10 mg daily (>80%) and maintained this dose (>80%). CONCLUSIONS: In the real world, everolimus was used in more severe patients than ET but less severe patients than CT based on visceral metastasis, tumor volume, and performance status. The top reason for prescribing everolimus was efficacy. A large proportion of patients received first or second line CT before everolimus initiation. The majority of patients used everolimus according to the labeled combination and dose. Future studies are needed to determine optimal sequencing of everolimus, ET, and CT for HR+/HER2- mBC.

Everolimus-Based Therapy versus Chemotherapy among Patients with HR+/HER2- Metastatic Breast Cancer: Comparative Effectiveness from a Chart Review Study.

Objective. To compare the real-world effectiveness of everolimus-based therapy and chemotherapy in postmenopausal women with hormone-receptor-positive/human-epidermal-growth-factor-receptor-2-negative (HR+/HER2-) metastatic breast cancer (mBC). Methods. This retrospective chart review examined a nationwide sample of postmenopausal HR+/HER2- mBC women in community-based oncology practices. Patients received everolimus-based therapy or chemotherapy for mBC between 07/01/2012 and 04/15/2013, after failure of a non-steroidal aromatase inhibitor. Overall survival (OS), progression-free survival (PFS), and time on treatment (TOT) were compared using Kaplan-Meier analysis and Cox proportional hazards models adjusting for line of therapy and baseline characteristics. Results. 234 and 137 patients received everolimus-based therapy and chemotherapy. Patients treated with everolimus-based therapy tended to have less aggressive mBC than patients treated with chemotherapy. Multivariate-adjusted Cox models showed that everolimus-based therapy was associated with significantly longer OS [hazard ratio (HR) = 0.37, 95% confidence interval (CI): 0.22-0.63], PFS (HR = 0.70, 95% CI = 0.50-0.97), and TOT (HR = 0.34, 95% CI: 0.25-0.45) than chemotherapy. Adjusted comparative effectiveness results were generally consistent across lines of therapy. Conclusion. In this retrospective chart review of postmenopausal HR+/HER2- mBC patients, treatment with everolimus-based therapy was associated with longer OS, PFS, and TOT than chemotherapy.

Comparative effectiveness of everolimus-based therapy versus endocrine monotherapy among postmenopausal women with HR+/HER2- metastatic breast cancer: a retrospective chart review in community oncology practices in the US.

BACKGROUND: Everolimus-based therapy and endocrine monotherapy are used among postmenopausal women with hormone receptor-positive human epidermal growth factor receptor-2 negative (HR+/HER2-) metastatic breast cancer (mBC) whose disease progressed or recurred on a non-steroidal aromatase inhibitor (NSAI). However, limited evidence exists regarding the real-world comparative effectiveness of these agents. METHODS: This retrospective chart review examined postmenopausal HR+/HER2- mBC patients in community-based oncology practices who received everolimus-based therapy or endocrine monotherapy (index therapy) as any line of therapy for mBC between 1 July 2012 and 15 April 2013 after NSAI failure. Time on treatment (TOT), progression-free survival (PFS), and time to chemotherapy (TTC) from index therapy initiation were compared using Kaplan-Meier analyses and Cox proportional hazards models adjusting for baseline characteristics. RESULTS: A total of 243 and 270 patients received everolimus-based therapy or endocrine monotherapy in a quota-based sample. Patients treated with everolimus-based therapy had a higher proportion of visceral metastases, high tumor burden, and use of prior chemotherapies for mBC. After adjusting for baseline characteristics, everolimus-based therapy was associated with significantly longer TOT (HR = 0.67, 95% CI: 0.51-0.87) and PFS (HR = 0.75, 95% CI: 0.57-0.98) than endocrine monotherapy. No significant difference was found between everolimus-based therapy and endocrine monotherapy in TTC (HR = 0.81, 95% CI: 0.52-1.27). Results stratified by line of therapy were generally consistent with the overall results. LIMITATIONS: Limitations include recall and information bias with potentially absent or erroneous chart data, unobserved factors due to non-randomization, inability to measure outcome assessments paired with measuring outcomes prior to exposures, and potential patient selection bias associated with chart review. CONCLUSIONS: Among a nationwide sample of postmenopausal HR+/HER2- mBC patients treated in community oncology settings, treatment with everolimus-based therapy was associated with significantly longer TOT and PFS compared to endocrine monotherapy.

Prognostic factors for survival following initiation of second-line treatment with everolimus for metastatic renal cell carcinoma: evidence from a nationwide sample of clinical practice in the United States.

OBJECTIVE: Comparing prognostic factors for overall survival (OS) in community-practice metastatic renal cell carcinoma (mRCC) patients receiving second-line everolimus with those previously reported in clinical trials. RESEARCH DESIGN AND METHODS: Two separate chart sets (2009 - 2012) were used to develop and validate a prognostic model for patients initiating second-line everolimus after first-line tyrosine kinase inhibitor (TKI). MAIN OUTCOME MEASURES: Prognostic factors for OS have been identified and validated in separate samples. RESULTS: One-year OS probabilities in the study (n = 220) and validation (n = 97) samples were 68 and 67%; median OS was 19 and 23 months - higher than the 1-year OS of 60% and median OS of 14.8 months of RECORD-1. Karnofsky performance score < 80%, duration of mRCC < 1 year, progression on first-line TKI, liver metastasis and clear cell histology were significant prognostic factors for shorter survival. One-year OS estimates were 84% for validation sample patients with 0 - 2 risk factors, 63% for 3 risk factors and 22% for 4 - 5 risk factors (log-rank p < 0.001). CONCLUSION: Real-world prognostic factors for OS following second-line everolimus for mRCC were largely consistent with those previously identified in trial data; however, OS was longer in the practice setting than in clinical trials and was not associated with type of first-line TKI.

Treatment patterns and duration in post-menopausal women with HR+/HER2- metastatic breast cancer in the US: a retrospective chart review in community oncology practices (2004-2010).

BACKGROUND: Clinical guidelines prefer endocrine therapy (ET) as initial treatment for post-menopausal women with hormone receptor positive (HR+)/human epidermal growth factor receptor 2 negative (HER2-) metastatic breast cancer (mBC). Chemotherapy (CT) should be reserved for patients who develop symptomatic visceral disease or have no clinical benefit after three sequential ET regimens. It is unclear if real-world clinical practice reflects these guidelines. OBJECTIVE: To describe treatment patterns and treatment durations by lines of therapy for ET and CT among post-menopausal HR+/HER2- mBC patients. METHODS: Charts were reviewed from a network of community-based oncology practices of eligible patients who had progressed after initiating adjuvant or first-line treatment for mBC between 1 January 2004 and 30 September 2010. Extracted chart data included demographics, treatment histories, and outcomes. Treatment duration was estimated using Kaplan-Meier estimators. RESULTS: A total of 144 patients were studied. Patients received a median of two lines of ET, and <10% had three or more lines of ET before receiving CT. From first line to second line, the median treatment duration was 11.6 to 4.9 months for ET overall; 13.8 to 10.5 months for anastrozole; 18.6 to 7.0 months for letrozole; and 5.1 to 2.9 months for fulvestrant. For CT, the median duration was 5.1 months in the first line and 3.7 months and below in subsequent lines. CONCLUSION: During the study period (1 January 2004 - 30 September 2012), most patients received <3 lines of ET before receiving CT. The drop in median duration of ET from first to second line suggests that single agent ETs might not be as effective beyond the first line. A key limitation of this study was the small sample size. In addition, more research is needed to further investigate the short treatment duration of fulvestrant across early lines of therapy (which could indicate lack of efficacy).

Comparative effectiveness of second-line targeted therapies for metastatic renal cell carcinoma: synthesis of findings from two multi-practice chart reviews in the United States.

BACKGROUND: Second-line targeted therapies for metastatic renal cell carcinoma (mRCC) include mammalian target of rapamycin (mTOR) inhibitors and tyrosine kinase inhibitors (TKIs). This study compares the effectiveness of these therapies in a multi-practice chart review and synthesizes the findings with those of a similarly designed study. METHODS: Medical oncologists/hematologists (N = 36) were recruited to review charts for patients aged ≥18 years, received a first-line TKI and initiated second-line targeted therapy in 2010 or later. The primary outcome was time from second-line initiation to treatment failure (TTF; discontinuation, physician-assessed progression, or death, whichever occurred first). TTF was compared among patients receiving second-line everolimus (EVE), temsirolimus (TEM), or TKI as a class, using a Cox proportional hazards model adjusting for type of initial TKI and response, histological subtype, performance status, and sites of metastasis. Hazard ratios (HRs) for TTF were pooled, in a meta-analysis, with previously reported HRs for progression-free survival from a chart review with a similar design. RESULTS: A total of 138, 64 and 79 patients received second-line therapy with EVE, TEM or a TKI, respectively. Adjusting for baseline characteristics, EVE was associated with numerical, but not statistically significant, reductions of 28% (HR = 0.72; 95% CI [0.45-1.16]) and 26% (HR = 0.74; 95% CI [0.48-1.15]) in the hazard of TTF compared to TEM and TKI, respectively. After pooling the HRs from both studies, EVE was associated with significantly reduced hazards of TTF compared to TEM and TKI (HR = 0.73; 95% CI [0.57-0.93]; and HR = 0.75; 95% CI [0.57-0.98], respectively). LIMITATIONS: LIMITATIONS include retrospective analyses with possible missing or erroneous chart data, confounding of unobserved factors due to non-randomization, and limited data for axitinib during the study period. CONCLUSIONS: In pooled results from two independent multi-practice chart reviews of second-line mRCC treatment, EVE was associated with significantly reduced hazards of treatment failure compared to TEM and to TKIs as a class.

Treatment patterns in metastatic renal cell carcinoma: a retrospective review of medical records from US community oncology practices.

BACKGROUND: Vascular endothelial growth factor (VEGF) inhibitors, including targeted therapy with tyrosine kinase inhibitors (TKIs) and the angiogenesis inhibitor bevacizumab, and mammalian target of rapamycin (mTOR) inhibitors are now the standard of care for metastatic renal cell carcinoma (mRCC). However, real-world treatment patterns are not well characterized. OBJECTIVE: To describe treatment patterns during the first, second, and third lines of targeted therapies for mRCC among community oncologists in the US. METHODS: Participating physicians recruited from a nationwide panel each identified up to 15 adult mRCC patients who initiated a second therapy after January 2010. Information extracted from medical records included types of targeted therapies, reasons for treatment choices, patterns of treatment discontinuation, and dose adjustments. RESULTS: Thirty-six physicians contributed charts from 433 mRCC patients. Seventy-seven percent of patients received a VEGF inhibitor as first targeted therapy; 23% received an mTOR inhibitor. Among first-line VEGF users, second-line treatments were 66% mTOR and 34% VEGF inhibitors. Among first-line mTOR users, second-line treatments were 94% VEGF and 6% mTOR inhibitors. Sunitinib followed by everolimus was the most commonly used treatment sequence. Estimated median duration for second targeted therapy was 8.6 months, and median overall survival (OS) and progression-free survival (PFS) were 27.4 and 10.8 months, respectively. Efficacy, treatment guidelines and mechanism of action were the most important considerations for treatment choice. LIMITATIONS: LIMITATIONS include no adjustment for baseline characteristics, possible difference between physician-defined progression and central review in the clinical trial setting, and limited data availability for axitinib during the study period. CONCLUSION: In this large retrospective chart review among community oncologists, VEGF-mTOR-VEGF was the most common treatment sequence for mRCC. The most common drugs were sunitinib in the first line and everolimus in the second line.

Functionality and health-status benefits associated with reduction of osteoarthritis pain.

OBJECTIVE: To evaluate the association between pain intensity improvement and improvements in functionality and health status in patients with chronic osteoarthritis pain of the hip or knee. METHODS: Data were obtained from a 12-week, randomized, double-blind, placebo-controlled study of tramadol ER 100 mg, 200 mg, 300 mg, or 400 mg once daily. Patients reported pain intensity with a 100-mm visual analog scale (0 = no pain, 100 = extreme pain) and functionality and health status with the disease-specific Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) questionnaire and the generic Short-Form-36 Health Survey (SF-36). Pain intensity improvement from baseline was categorized as < 0%, 0-14%, 15-29%, 30-49%, 50-69%, and >or= 70%, and mean changes in WOMAC and SF-36 scores were determined for patients in each category. RESULTS: A total of 1011 patients received placebo (n = 205) or tramadol ER 100 mg (n = 202), 200 mg (n = 201), 300 mg (n = 201), or 400 mg (n = 202). The degree of pain intensity improvement was correlated with the degree of improvement in WOMAC and SF-36 scores; as little as 15% reduction of pain intensity was associated with notable improvements in function and health status. Potential limitations included the lack of established thresholds to assess clinically meaningful changes in these outcomes. CONCLUSIONS: Pain intensity improvement is associated with corresponding improvements in function and health status. While large improvements in pain intensity are associated with large improvements in health status and functionality, modest pain reductions are also associated with improvement of certain health status parameters.

Validation of the Migraine-Specific Quality of Life Questionnaire version 2.1 (MSQ v. 2.1) for patients undergoing prophylactic migraine treatment.

OBJECTIVE: Health-related quality of life (HRQoL) is an important outcome measure of migraine treatments. Although a number of migraine-specific HRQoL questionnaires exist, their measurement characteristics have only been examined for patients undergoing acute treatment of migraine. The goal of the current study was to evaluate measurement properties of the widely used Migraine-Specific Quality of Life Questionnaire version 2.1 (MSQ v. 2.1) within a group of patients undergoing prophylactic migraine treatment. METHODS: Various measurement properties of the MSQ were examined in a sample of 916 migraineurs undergoing prophylactic treatment who had scores at baseline and follow-up, as well as baseline SF-36. First, we used confirmatory factor analysis (CFA) and differential item functioning (DIF) to assure the accuracy and stability across groups of the MSQ scoring for all three subscales (Role Restrictive, Role Preventive, and Emotional Functioning). Next, item- and scale-level properties were examined, such as item-total correlations, internal consistency, and convergent and discriminant validity. RESULTS: Initial findings revealed that item 12 (measuring frustration on the Emotional Functioning subscale) performed poorly. Subsequent to its removal, the 13-item MSQ displayed excellent measurement properties, including stable latent structure at baseline and endpoint, no gender or age biases on items, appropriate item-level and scale-level reliabilities, and markedly higher convergent validity compared to discriminant validity. CONCLUSION: The 13-item MSQ appears to be an appropriate measure of migraine-specific HRQoL for patients undergoing migraine prophylaxis. Moreover, given the stability of the latent structure over time, the interpretation of scores is likely to remain quite consistent throughout a clinical trial.

Interpreting score differences in the SF-36 Vitality scale: using clinical conditions and functional outcomes to define the minimally important difference.

OBJECTIVE: To propose the minimally important difference (MID) for the SF-36 Vitality (VT) scale by evaluating the association of score differences with clinical conditions and functional outcomes. METHODS: Analyses were performed on data from the Medical Outcomes Study (n = 3445). The first analyses regressed VT scores (0-100 scale) on chronic conditions that cause fatigue in order to determine the impact of each condition on VT. The second set of analyses examined the relationship between baseline VT scores and other outcomes at baseline, 1-year, and 7-year follow-up. RESULTS: VT scores were significantly reduced in patients with anemia [5 points (95% CI 2-9 points)], CHF [6 (3-9) points], and COPD [6 (3-9) points]. Decreases in VT score were significantly associated with increased odds of negative outcomes, including inability to work due to health at baseline [OR (5 points) = 1.27 (95% CI 1.24-1.31), OR (10 points) = 1.62 (1.54-1.71)], job loss at 1 year [OR (5) = 1.13 (1.08-1.19), OR (10) = 1.28 (1.17-1.41)], hospitalization at 1 year [OR (5) = 1.08 (1.05-1.11), OR (10) = 1.17 (1.10-1.23)], short-term mortality [0-18 months-Hazard Ratio (HR) (5) = 1.10-1.71, HR (10) = 1.21-2.39, depending on VT level] and long-term mortality [19+ months-HR (5) = 1.05-1.31, HR (10) = 1.10-1.54]. The mortality risk increase was largest at low VT levels. CONCLUSIONS: VT decrements of 5-10 points were seen for diseases known to cause fatigue. Further, differences of 5-10 points in the VT score were associated with significant increased risk of negative outcomes. We recommend an MID of 5 points for analyses of groups with VT scores below average. For follow-up of individual patients, we recommend a 10-point difference as important.