Dosing patterns, toxicity, and outcomes in patients treated with first-line sunitinib for advanced renal cell carcinoma in community-based practices.

BACKGROUND: This retrospective study by McKesson Specialty Health (MSH)/US Oncology Network (USON) evaluates dosing patterns of first-line sunitinib for patients with advanced renal cell carcinoma (aRCC) and its association with toxicities and clinical outcomes in community practices. PATIENTS AND METHODS: Patients with aRCC who started first-line sunitinib between June 1, 2007, and May 31, 2011, were identified from 17 MSH/USON practices. Clinical data were extracted from iKnowMed electronic medical records linked to the MSH/USON pharmacy database. RESULTS: In total, 134 patients were included; mean age was 63.9 years, 85% of the patients had an Eastern Cooperative Oncology Group performance score of 0 or 1, 82% had clear-cell renal cell carcinoma, and 65% had undergone nephrectomy. The median treatment duration was 4 cycles (range, 1-19). Overall, 113 patients discontinued sunitinib, mainly because of disease progression (45.1%) or toxicities (16.8%). Of all discontinuations, 77% occurred within the first 5 cycles. A total of 45 patients were dose-reduced, mostly because of toxicities (93%); 67% of all dose reductions occurred in the first 3 cycles. The objective response rate was 16.4%, median overall survival (OS) was 15.5 months, and progression-free survival (PFS) was 7.5 months. Multivariate analysis showed that OS and PFS were associated with sunitinib treatment duration. CONCLUSIONS: Patients with aRCC from community practices undergo sunitinib dose reductions more frequently because of toxicities and discontinue therapy sooner than in clinical trials. Clinical outcomes were inferior to those reported in clinical trials, potentially because of shorter duration of therapy. Sunitinib therapy optimization remains an important challenge in community practices.

Evaluating use characteristics for the oncotype dx 21-gene recurrence score and concordance with chemotherapy use in early-stage breast cancer.

PURPOSE: Oncotype Dx 21-gene assay recurrence score (RS) predicts recurrence of early-stage breast cancer (ESBC). We investigated whether patient, tumor, or practice characteristics drive its use and explored Oncotype DX RS and chemotherapy use in subgroups. METHODS: Patients with ESBC with documented estrogen receptor-positive, lymph node-negative, human epidermal growth factor receptor 2-negative tumors registered within McKesson Specialty Health's iKnowMed electronic health record were included. Patient and practice characteristics by region and size were analyzed. The association between Oncotype DX RS value and use of chemotherapy were assessed. RESULTS: The study included 6,229 patients. Of these, 1,822 (29%) had an Oncotype DX RS result. Test use was 36%, 38%, 34%, 25%, and 6%, respectively, in patients age ≤ 45, 46-55, 56-65, 66-75, and ≥ 76 years; 33%, 25%, and 9% in patients with Eastern Cooperative Oncology Group performance status of 0, 1, and ≥ 2; 7%, 9%, 25%, 38%, 27%, and 10% in T1mic, T1a, T1b, T1c, T2, and T3 tumors; and 26%, 32%, and 33% for grades 1, 2, and 3 tumors. Of the 1,822 patients with available Oncotype DX RS, adjuvant chemotherapy use was 6%, 42%, and 84% in the low-, intermediate-, and high-risk groups. CONCLUSION: Patients who were younger, had better ECOG performance status, or had higher grade tumors were more likely to undergo RS testing. It appears that the RS test may have influenced the decision about whether to administer adjuvant chemotherapy: a low RS score was associated with lower chemotherapy use and a high RS score was associated with higher chemotherapy use.

Demographics, treatment patterns, safety, and real-world effectiveness in patients aged 70 years and over with chronic lymphocytic leukemia receiving bendamustine with or without rituximab: a retrospective study.

OBJECTIVES: Bendamustine is a unique cytotoxic agent active against various human malignancies, including chronic lymphocytic leukemia (CLL). In vitro studies suggest that cytotoxic activity of bendamustine on CLL-derived cells is synergized by rituximab. A retrospective chart review was conducted to characterize treatment-naïve outpatients and those with relapsed disease aged 70 years and over with CLL receiving bendamustine (with or without rituximab) and to evaluate real-world patterns of care, safety, and effectiveness. METHODS: Using McKesson Specialty Care/US Oncology Network iKnowMed databases, 91 outpatients with at least two recorded visits and at least two cycles of bendamustine monotherapy or bendamustine-rituximab combination therapy were identified and included. Mean age at diagnosis and start of first therapy was 70.3 and 77.4 years respectively, and 63.7% of patients were men. RESULTS: Observed overall response rate was 56.3% in pooled treatment-naïve patients [n = 9; complete response (CR) 18.8%; partial response (PR) 37.5%; nodular partial response (nPR) 0%] and 58.7% in pooled patients with relapsed disease (n = 44; CR 13.3%; PR 44.0%; nPR 1.3%). Median time to progressive disease has not been reached for the 16 treatment-naïve patients (median follow up 15.1 months), and was 18.4 months for those with relapsed disease (n = 73). No unexpected toxicities were observed. Overall rate of blood/bone marrow toxicities (all grades) was 40.7%; grade 3/4 rates were 18.8% in treatment-naïve patients and 25.3% in those with relapsed disease. Most frequent nonhematologic adverse events were fatigue and rash. CONCLUSION: In this retrospective chart review of 91 outpatients with CLL aged 70 years and over, bendamustine (with or without rituximab) was an effective therapeutic option with manageable toxicity.

Survival outcomes of bevacizumab beyond progression in metastatic colorectal cancer patients treated in US community oncology.

BACKGROUND: Bevacizumab prolongs OS when added to first- or second-line chemotherapy for mCRC. This retrospective analysis evaluated the association between the continued use of BBP and survival outcomes in mCRC patients treated in a community oncology setting. PATIENTS AND METHODS: Data were derived from the US Oncology iKnowMed electronic medical record system. Patients with mCRC who received first-line bevacizumab-containing therapy between July 1, 2006 and June 30, 2009, were dichotomized into 2 second-line treatment cohorts: those receiving BBP and No-BBP. Clinical outcomes, including OS and postprogression OS (ppOS; time from start of second-line therapy to any-cause death), were calculated using Kaplan-Meier methods. A Cox proportional hazards model was used to assess the effects of patient and treatment characteristics on survival outcomes, adjusting for covariates. RESULTS: Overall, 573 patients met the inclusion criteria for analysis-BBP (n = 267) and No-BBP (n = 306). Median OS and ppOS were longer in the BBP cohort (27.9 and 14.6 months, respectively) compared with the No-BBP cohort (21.4 and 10.1 months). According to multivariate analyses, BBP was associated with longer OS (HR, 0.76; 95% CI, 0.61-0.95) and ppOS (HR, 0.74; 95% CI, 0.60-0.93) after adjusting for potential confounders. CONCLUSIONS: In the community oncology setting, BBP treatment was correlated with prolonged OS and ppOS in patients with mCRC. These results provide insight into real-world patterns of care and resultant bevacizumab use in this patient population.

Costs and clinical outcomes among patients with second-line non-small cell lung cancer in the outpatient community setting.

INTRODUCTION: A comparison of clinical and economic outcomes among patients receiving second-line monotherapy with erlotinib, docetaxel, and pemetrexed for non-small cell lung cancer was conducted using a large network of outpatient community clinics. METHODS: We identified 610 patients with advanced non-small cell lung cancer who received 2L treatment from July 1, 2006, to June 30, 2008, and were followed up through July 1, 2009, to evaluate progression-free survival (PFS), overall survival (OS), costs, and health resource utilization. Cox proportional hazards regression were used to compare PFS and OS across treatment cohorts. Economic outcomes were calculated per patient per month (PPPM) during a 12-month follow-up period. RESULTS: There were 73 patients who received erlotinib, 87 received docetaxel, and 450 received pemetrexed. The median age was 67 years, and 55% were men. No significant differences in stage, baseline performance status, hemoglobin level, or body mass index were observed by treatment. The median OS was 132 days for docetaxel, 132 days for pemetrexed, and 155 days for erlotinib (p = 0.39). Adjusting for age, gender, stage, performance status, and hemoglobin level, there was no significant association between treatment type and OS (p = 0.36) or PFS (p = 0.26). Relative to pemetrexed, total adjusted costs PPPM was $1579 lower for docetaxel and $1584 lower for erlotinib (p < 0.05). Outpatient visits, laboratory procedures, and acute care visits were also less frequent with erlotinib relative to pemetrexed (-2.6 PPPM, p < 0.05). CONCLUSIONS: We observed no significant differences in OS and PFS between patients receiving erlotinib, docetaxel, and pemetrexed. Nevertheless, erlotinib and docetaxel were associated with a statistically significant lower costs and resource use relative to pemetrexed.

Economic impact of disease progression in follicular non-Hodgkin lymphoma.

Using a retrospective claims database, we estimated the economic costs of progression among patients with follicular non-Hodgkin lymphoma (f-NHL) treated in an outpatient community-based setting. Patients with f-NHL who received care between 1 July 2006 and 31 December 2009 were categorized into two cohorts based on whether they experienced progressive disease (PD) or not. Costs per patient per month (PPPM) were compared between patients with PD versus non-PD. Follow-up time was censored at the last entry for disease status or 6 months after the date of remission/stable disease or progression. Of the 1002 patients with f-NHL identified, 268 progressed and 734 did not. The mean overall costs PPPM over the 6-month follow-up period were significantly higher for patients with PD versus non-PD ($3527 vs. $860; difference = $2667; p < 0.001). This cost difference persisted within all resource categories evaluated. Results of this study indicate that therapies which delay progression for patients with f-NHL may result in potential cost savings.

Evaluation of the Reliability of Electronic Medical Record Data in Identifying Comorbid Conditions among Patients with Advanced Non-Small Cell Lung Cancer.

Background. Traditional methods for identifying comorbidity data in EMRs have relied primarily on costly and time-consuming manual chart review. The purpose of this study was to validate a strategy of electronically searching EMR data to identify comorbidities among cancer patients. Methods. Advanced stage NSCLC patients (N = 2,513) who received chemotherapy from 7/1/2006 to 6/30/2008 were identified using iKnowMed, US Oncology's proprietary oncology-specific EMR system. EMR data were searched for documentation of comorbidities common to advanced stage cancer patients. The search was conducted by a series of programmatic queries on standardized information including concomitant illnesses, patient history, review of systems, and diagnoses other than cancer. The validity of the comorbidity information that we derived from the EMR search was compared to the chart review gold standard in a random sample of 450 patients for whom the EMR search yielded no indication of comorbidities. Negative predictive values were calculated. Results. The overall prevalence of comorbidities of 22%. Overall negative predictive value was 0.92 in the 450 patients randomly sampled patients (36 of 450 were found to have evidence of comorbidities on chart review). Conclusion. Results of this study suggest that efficient queries/text searches of EMR data may provide reliable data on comorbid conditions among cancer patients.

Bevacizumab treatment to progression after chemotherapy: outcomes from a U.S. community practice network.

Bevacizumab significantly extends progression-free survival (PFS) and overall survival (OS) times when combined with initial chemotherapy and continued as monotherapy until disease progression or unacceptable toxicity in patients with nonsquamous non-small cell lung cancer (NSCLC). In clinical practice, bevacizumab is sometimes discontinued after completion of chemotherapy. This retrospective analysis of the US Oncology network's electronic medical records evaluated the association between PFS and OS times and bevacizumab monotherapy to progression (BTP) among patients with advanced NSCLC. Patients treated from July 2006 through June 2008 were analyzed as two cohorts based on whether or not they received BTP after completion of first-line chemotherapy plus bevacizumab. Hazard ratios for PFS and OS were estimated using Cox proportional hazards, adjusting for relevant treatment and patient characteristics. To account for survivorship bias, landmark analyses were conducted at 18, 21, and 26 weeks from initial therapy to examine residual PFS and OS times, defined as the time from the landmark to disease progression or death. From the total 498 nonsquamous NSCLC patients, 403 received first-line chemotherapy plus bevacizumab: 154 received BTP, 249 did not. Longer PFS and OS times were observed in patients who received BTP than in those who received no BTP (median OS, 20.9 months versus 10.2 months; median PFS, 10.3 months versus 6.5 months). BTP was associated with a longer residual OS time at all specified landmarks and longer residual PFS time at week 18 than with no BTP. In conclusion, this retrospective analysis provides supportive evidence that continued vascular endothelial growth factor suppression in advanced nonsquamous NSCLC patients is associated with favorable clinical outcomes.

Cost effectiveness of evidence-based treatment guidelines for the treatment of non-small-cell lung cancer in the community setting.

PURPOSE: The goal of this study was to evaluate the cost-effectiveness of Level I Pathways, a program designed to ensure the delivery of evidence-based care, among patients with non-small-cell lung cancer (NSCLC) treated in the outpatient community setting. PATIENTS AND METHODS: We included patients with NSCLC initiating a chemotherapy regimen between July 1, 2006, and December 31, 2007, at eight practices in the US Oncology network. Patients were characterized with respect to age, sex, stage, performance status, and line of therapy and were classified by whether they were treated according to Level I Pathways guidelines. Twelve-month cost of care and overall survival were compared between patients treated on Pathway and off Pathway. A net monetary benefit approach and corresponding cost-effectiveness acceptability curves were used to evaluate the cost-effectiveness of Level I Pathways. RESULTS: Overall, outpatient costs were 35% lower for on-Pathway versus off-Pathway patients (average 12-month cost, $18,042 v $27,737, respectively). Costs remained significantly less for patients treated on Pathway versus off Pathway in the adjuvant and first-line settings, whereas no difference in overall cost was observed in patients in the second-line setting. No difference in overall survival was observed overall or by line of therapy. In the net monetary benefit analysis, after adjusting for potential confounders, we found that treating patients on Pathway was cost effective across a plausible range of willingness-to-pay thresholds. CONCLUSIONS: Results of this study suggest that treating patients according to evidence-based guidelines is a cost-effective strategy for delivering care to those with NSCLC.

Cognitive-behavioral therapy versus temporal pulse amplitude biofeedback training for recurrent headache.

Sixty-four headache sufferers were allocated randomly to cognitive-behavioral therapy (CBT), temporal pulse amplitude (TPA) biofeedback training, or waiting-list control. Fifty-one participants (14M/37F) completed the study, 30 with migraine and 21 with tension-type headache. Treatment consisted of 8, 1-hour sessions. CBT was highly effective, with an average reduction in headaches from pre- to posttreatment of 68%, compared with 56% for biofeedback, and 20% for the control condition. Headaches continued to decrease to 12 month follow-up for CBT. Improvement with CBT was associated with baseline coping skills, social support, and physiological measures at rest and in response to stress, particularly TPA. Changes on some of these measures were correlated with changes in headaches. No significant predictors of response to biofeedback emerged.

Noise as a trigger for headaches: relationship between exposure and sensitivity.

OBJECTIVE: This study investigated how triggers acquire the capacity to precipitate headaches. BACKGROUND: Traditional clinical advice is that the best way to prevent headache/migraine is to avoid the triggers. Avoidance of anxiety-eliciting stimuli, however, results in sensitization to the stimuli, so is there a danger that avoidance of migraine/headache triggers results in decreased tolerance for the triggers? DESIGN: One hundred and fifty subjects, 60 of whom suffered from regular headaches, were randomly assigned to 5 experimental conditions, defined by length of exposure to the headache trigger of noise. METHODS: Subjects attended a laboratory session divided into 3 phases: preintervention test, intervention (1 of 5 levels of exposure to the trigger), and postintervention test. Response to the intervention was measured in terms of noise tolerance, sensitivity to noise, and nociceptive response to noise. RESULTS: A curvilinear relationship was found between length of exposure to the trigger and pain response for individuals who do not suffer from regular headaches, that is, short exposure was associated with sensitization and prolonged exposure with desensitization. The relationship for headache patients was less clear. CONCLUSIONS: The findings are consistent with the proposition that 1 etiological pathway to suffering from frequent headaches is via trying to avoid, or escape from, potential trigger factors. These results suggest that the traditional clinical advice to headache patients, that the best way to prevent migraine/headache is to avoid the triggers, runs the risk of establishing an insidious sensitization process thereby increasing headache frequency.