BACKGROUND: Granulocyte colony-stimulating factors such as filgrastim are used to decrease the incidence of febrile neutropenia (FN) among patients with nonmyeloid cancers undergoing chemotherapy treatment. Although the biosimilar filgrastim-sndz has been approved in the United States since 2015, limited real-world comparisons of filgrastim-sndz versus reference filgrastim (filgrastim-ref) have been conducted.
OBJECTIVE: To compare FN incidence and assess overall FN-related health care resource utilization and medical costs among U.S. patients with non-myeloid cancer who received filgrastim-sndz or filgrastim-ref during their first chemotherapy cycle.
METHODS: This was a retrospective claims analysis of patients with non-myeloid cancer who were enrolled in commercial or Medicare Advantage insurance plans from March 2015 through June 2016 and received filgrastim-sndz or filgrastim-ref during their first observed chemotherapy cycle. Patients with evidence of hematopoietic stem cell transplantation or pregnancy and those with missing demographic information were excluded. FN was defined on the basis of diagnosis codes for neutropenia and fever (N/F); neutropenia and infection (N/I); and neutropenia, infection, and fever (N/I/F). Cohorts were adjusted for differences in baseline patient characteristics using the inverse probability of treatment weighting (IPTW) method, and equivalence testing was used to compare the proportion of patients who developed FN between weighted cohorts. On the basis of the range of neutropenic fever incidence found in the PIONEER clinical trial, FN incidence was considered equivalent if 90% CIs for between-cohort differences were within ± 6%. Mean FN-related health care resource utilization and total FN-related medical costs were calculated for the overall study population.
RESULTS: A total of 3,542 patients were included in the study (172 filgrastim-sndz; 3,370 filgrastim-ref; mean ages 62.1 years and 64.7 years, respectively). After IPTW, there were 162 patients in the filgrastim-sndz cohort and 3,297 in the filgrastim-ref cohort (mean age 64.5 years for both). FN incidence in the weighted filgrastim-sndz versus filgrastim-ref cohorts, respectively, was 1.4% versus 0.9% for N/F, 2.3% versus 1.7% for N/I, and 0.0% versus 0.3% for N/I/F; FN incidence was statistically equivalent between treatment cohorts. Among patients in either treatment cohort who developed FN, the proportion with FN-related inpatient stays during the first chemotherapy cycle ranged from 35.0% for N/I to 70.0% for N/I/F. Mean (SD) FN-related total medical costs across all patients who developed FN were $11,977 ($18,383) for N/F, $8,040 ($14,809) for N/I, and $21,733 ($30,003) for N/I/F, in 2015 U.S. dollars. For all 3 definitions of FN, the largest proportions (73.5%-93.4%) of medical costs were inpatient related.
CONCLUSIONS: In this real-world study of patients with nonmyeloid cancers undergoing chemotherapy, the incidence of FN was statistically equivalent between individuals treated with filgrastim-sndz versus filgrastim-ref during their first chemotherapy cycle. FN-related health care resource utilization and medical costs among patients who developed FN were substantial.
DISCLOSURES: This work was funded by Sandoz, which participated in the study design, data interpretation, writing and revision of the manuscript, and decision to submit the manuscript for publication. Balu and Campbell are employees of Sandoz, which is the manufacturer of the filgrastim biosimilars Zarzio and Zarxio. DeLeon was an employee of Sandoz at the time this study was conducted. Lal, Brekke, Elliott, and Korrer are employees of Optum, which was contracted by Sandoz to conduct this study.
BACKGROUND: Breast cancer chemotherapy is associated with a decline in measured cardiorespiratory fitness and increased fatigue. Physical activity has emerged as a feasible intervention to limit these side effects. Quantitative evaluation is necessary to propose a better-adapted physical activity and to evaluate efficacy.
AIM: We undertook a prospective study to assess the effects of a home-based adapted physical activity (APA) program on aerobic capacity, strength, and fatigue in women treated with adjuvant or neoadjuvant chemotherapy for breast cancer versus usual care.
DESIGN: This was an open two-arm, randomized controlled trial.
SETTING: Study included outpatient groups in the Department of Physiology and Medical Oncology of a hospital in France.
POPULATION: Forty-four patients treated with adjuvant or neoadjuvant chemotherapy for breast cancer.
METHODS: Patients were randomly assigned to a control group or an APA group. Intervention consisted of a 3-week, home-based, supervised, combined APA program (endurance and resistance training) during 27 weeks. The primary endpoint was cardiopulmonary function assessed by maximal peak oxygen consumption (VO2peak). Secondary endpoints included a 6-minute Walking Test (6MWT), and assessment of muscular strength, fatigue, quality of life, physical activity level, and anxiety/depression.
RESULTS: At 27 weeks, VO2peak increased by 1.83±0.68 ml.min-1.kg-1 in the APA group (P=0.009) and decreased by 1.31±0.65 mL.min-1.kg-1 in the control group (P=0.046). The difference between the two groups was not significant (2.26±1.53 mL.min-1.kg-1, P=0.140) in intention-to-treat analysis, but it was significant in per protocol analysis (3.49±1.64 mL.min-1.kg-1, P=0.049). At 27 and 54 weeks, no significant differences were observed between the two groups for the cardiopulmonary exercise test, 6MWT, quadriceps strength, or quality of life.
CONCLUSIONS: In breast cancer patients, a home-based supervised program during chemotherapy and radiotherapy treatment may be safe, feasible and increase VO2peak. In this study, heavy evaluation tests explain patient's non-adherence and do not permit to obtain statistically significant results between APA and control groups.
CLINICAL REHABILITATION IMPACT: Aerobic home-based adapted physical activity is beneficial on aerobic capacity.
OBJECTIVES: The aim of the study was to evaluate the effects of a combined aerobic and strength program on physiological and psychological parameters in female breast cancer survivors. Study design: Randomised controlled trial. METHODS: 20 patients (age: 45.6 ± 2.7 yrs) surgically treated for breast cancer that had completed all cancer therapies at least 6 months before and with no contraindications to physical activity, were recruited and randomly assigned to an intervention group (n = 10) and a control group (n = 10). Intervention group patients attend to a 24-week combined aerobic and strength training program. Physiological (i.e. VO<sub>2max</sub>, bioelectrical impedance test, maximal strength of principal muscular groups) and psychological (i.e. functional assessment of chronic illness therapy-fatigue: FACIT-F) parameters were assessed at baseline and after 24 weeks. RESULTS: After 24 weeks the intervention group showed significant improvement in VO<sub>2max</sub> (38.8%), strength of upper and lower limbs (ranging from 13 to 60%) and decrease in fat mass percentage (6.3%). The FACIT-F showed significant increase in all of the three scores that can be derived (FACIT-F Trial outcome: 13%; FACT-G total score: 18%; FACIT-F total score: 15%) showing patient's quality of life (QOL) improvement. No significant change in all the parameters was found for the control group. CONCLUSION: These results show the positive effects of a combined aerobic and strength training program on breast cancer survivors and underline the importance of the early inclusion of structured physical activity in the rehabilitation protocol.
PURPOSE: Exercise decreases breast cancer risk and disease recurrence, but the underlying mechanisms are unknown. Training adaptations in systemic factors have been suggested as mediating causes. We aimed to examine if systemic adaptations to training over time, or acute exercise responses, in breast cancer survivors could regulate breast cancer cell viability in vitro.
METHODS: Blood samples were collected from breast cancer survivors, partaking in either a 6-month training intervention or across a 2 h acute exercise session. Changes in training parameters and systemic factors were evaluated and pre/post exercise-conditioned sera from both studies were used to stimulate breast cancer cell lines (MCF-7, MDA-MB-231) in vitro.
RESULTS: Six months of training increased VO2peak (16.4 %, p < 0.001) and muscle strength, and reduced resting levels of plasma cholesterol (-18.2 %, p = 0.003) and cytokines. Yet, these systemic adaptations had no effect on breast cancer cell viability in vitro. During 2 h of acute exercise, increases in serum lactate (6-fold, p < 0.001), epinephrine (2.9-fold, p = 0.009), norepinephrine (2.2-fold, p < 0.001), and cytokines, including IL-6 (2.1-fold, p < 0.001) were detected. Incubation with serum obtained after exercise reduced viability by -9.2 % in MCF-7 (p = 0.04) and -9.4 % in MDA-MB-231 (p < 0.001) compared to resting serum.
CONCLUSION: Systemic changes to a 2 h exercise session reduced breast cancer viability, while adaptations to 6 months of training had no impact. Our data question the prevailing dogma that training-dependent baseline reductions in risk factors mediate the protective effect of exercise on breast cancer. Instead, we propose that the cancer protection is driven by accumulative effects of repeated acute exercise responses.
<b>PURPOSE: </b>This study evaluated the effectiveness of a self-managed home-based moderate intensity walking intervention on psychosocial health outcomes among breast cancer patients undergoing chemotherapy.<b>METHODS: </b>The randomised controlled trial compared a self-managed, home-based walking intervention to usual care alone among breast cancer patients receiving chemotherapy. Outcome measures included changes in self-report measures of anxiety, depression, fatigue, self-esteem, mood and physical activity. Fifty participants were randomised to either the intervention group (n = 25), who received 12 weeks of moderate intensity walking, or the control group (n = 25) mid-way through chemotherapy. Participants in the intervention group were provided with a pedometer and were asked to set goals and keep weekly diaries outlining the duration, intensity and exertion of their walking. Levels of psychosocial functioning and physical activity were assessed pre- and post-intervention in both groups.<b>RESULTS: </b>The intervention had positive effects on fatigue (F = 5.77, p = 0.02), self-esteem (F = 8.93, p ≤ 0.001), mood (F = 4.73, p = 0.03) and levels of physical activity (x (2) = 17.15, p = 0.0011) but not anxiety (F = 0.90, p = 0.35) and depression (F = 0.26, p = 0.60) as assessed using the HADS. We found an 80% adherence rate to completing the 12-week intervention and recording weekly logs.<b>CONCLUSION: </b>This self-managed, home-based intervention was beneficial for improving psychosocial well-being and levels of physical activity among breast cancer patients treated with chemotherapy.<b>Trial Registration: </b>Current Controlled Trials ISRCTN50709297.
<b>BACKGROUND: </b>Exercise interventions improve fitness, functional capacity, and quality of life in patients with early-stage breast cancer, but to the authors' knowledge there are few data regarding the feasibility or potential benefits of exercise in women with metastatic breast cancer.<b>METHODS: </b>Individuals with metastatic breast cancer were randomized 1:1 to a 16-week moderate-intensity exercise intervention or wait-list control group. Intervention goals included 150 minutes of moderate-intensity aerobic exercise per week. The baseline and 16-week evaluations included a modified Bruce Ramp treadmill test, 7-day Physical Activity Recall interview, and European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (EORTC QLQ C-30) questionnaire.<b>RESULTS: </b>A total of 101 participants were randomized (48 to the intervention group and 53 to the control group). The median age of the participants was 49 years, the median time since the diagnosis of metastatic breast cancer was 1.1 years, and approximately 42% of participants were undergoing chemotherapy at the time of enrollment. Study attrition was higher in the intervention arm (14 participants vs 8 participants; P = .15). Women randomized to the exercise intervention experienced a nonsignificant increase with regard to minutes of weekly exercise (62.4 minutes vs 46.0 minutes; P = .17) and physical functioning (EORTC QLQ C30: 4.79 vs 0.93 [P = .23] and Bruce Ramp Treadmill test: 0.61 minutes vs 0.37 minutes [P = .35]) compared with control participants.<b>CONCLUSIONS: </b>Participation in an exercise intervention did not appear to result in significant improvements in physical functioning in a heterogeneous group of women living with advanced breast cancer. Given the significant benefits of exercise in women with early-stage breast cancer, more work is needed to explore alternative interventions to determine whether exercise could help women with metastatic disease live more fully with fewer symptoms from disease and treatment.
Multiple exercise interventions have shown beneficial effects on fatigue and quality of life (QoL) in cancer patients, but various psychosocial interventions as well. It is unclear to what extent the observed effects of exercise interventions are based on physical adaptations or rather on psychosocial factors associated with supervised, group-based programs. It needs to be determined which aspects of exercise programs are truly effective. Therefore, we aimed to investigate whether resistance exercise during chemotherapy provides benefits on fatigue and QoL beyond potential psychosocial effects of group-based interventions. One-hundred-one breast cancer patients starting chemotherapy were randomly assigned to resistance exercise (EX) or a relaxation control (RC) group. Both interventions were supervised, group-based, 2/week over 12 weeks. The primary endpoint fatigue was assessed with a 20-item multidimensional questionnaire, QoL with the EORTC QLQ-C30/BR23. Analyses of covariance for individual changes from baseline to Week 13 were calculated. In RC, total and physical fatigue worsened during chemotherapy, whereas EX showed no such impairments (between-group p = 0.098 and 0.052 overall, and p = 0.038 and 0.034 among patients without severe baseline depression). Differences regarding affective or cognitive fatigue were not significant. Benefits of EX were also seen to affect role and social function. Effect sizes were between 0.43 and 0.48. Explorative analyses indicated significant effect modification by thyroxin use (p-interaction = 0.044). In conclusion, resistance exercise appeared to mitigate physical fatigue and maintain QoL during chemotherapy beyond psychosocial effects inherent to supervised group-based settings. Thus, resistance exercise could be an integral part of supportive care for breast cancer patients undergoing chemotherapy.
BACKGROUND: Participation in physical activity can improve the health outcomes of breast cancer survivors. To impact public health, broad‐reaching sustainable interventions that promote physical activity are needed. Purpose To evaluate the efficacy of two distance‐based interventions for promoting physical activity among breast cancer survivors compared with a standard recommendation control. METHODS: Breast cancer survivors who had finished ‘active’ cancer treatment were eligible to participate. Participants (<i>n</i> = 330) were randomly assigned to receive one of the following mail‐delivered interventions: three computer‐tailored newsletters, a previously developed breast cancer‐specific physical activity booklet or a pamphlet detailing the public health recommendations for physical activity (control). Primary outcomes were self‐reported moderate to vigorous aerobic activity and participant's self‐reported resistance training activity at 4 months post‐baseline. Secondary outcomes were pedometer step counts, whether or not participants were meeting the physical activity guidelines, time spent in sedentary behaviour, fatigue and health‐related quality of life. RESULTS: Participants randomised into the tailored‐print intervention group were three times more likely to commence resistance training and meet the resistance‐training guidelines immediately after the intervention than participants allocated to the control group. There were no other significant intervention effects. CONCLUSION: Computer‐tailored newsletters may be an effective strategy for enhancing resistance‐based physical activity among breast cancer survivors. The null findings relating to other outcomes may be due to ceiling effects (in the case of aerobic activity, fatigue and health‐related quality of life) or the sensitivity of the measure used (in the case of sitting time). These issues require further exploration. (PsycInfo Database Record (c) 2021 APA, all rights reserved)
Granulocyte colony-stimulating factors such as filgrastim are used to decrease the incidence of febrile neutropenia (FN) among patients with nonmyeloid cancers undergoing chemotherapy treatment. Although the biosimilar filgrastim-sndz has been approved in the United States since 2015, limited real-world comparisons of filgrastim-sndz versus reference filgrastim (filgrastim-ref) have been conducted.
OBJECTIVE:
To compare FN incidence and assess overall FN-related health care resource utilization and medical costs among U.S. patients with non-myeloid cancer who received filgrastim-sndz or filgrastim-ref during their first chemotherapy cycle.
METHODS:
This was a retrospective claims analysis of patients with non-myeloid cancer who were enrolled in commercial or Medicare Advantage insurance plans from March 2015 through June 2016 and received filgrastim-sndz or filgrastim-ref during their first observed chemotherapy cycle. Patients with evidence of hematopoietic stem cell transplantation or pregnancy and those with missing demographic information were excluded. FN was defined on the basis of diagnosis codes for neutropenia and fever (N/F); neutropenia and infection (N/I); and neutropenia, infection, and fever (N/I/F). Cohorts were adjusted for differences in baseline patient characteristics using the inverse probability of treatment weighting (IPTW) method, and equivalence testing was used to compare the proportion of patients who developed FN between weighted cohorts. On the basis of the range of neutropenic fever incidence found in the PIONEER clinical trial, FN incidence was considered equivalent if 90% CIs for between-cohort differences were within ± 6%. Mean FN-related health care resource utilization and total FN-related medical costs were calculated for the overall study population.
RESULTS:
A total of 3,542 patients were included in the study (172 filgrastim-sndz; 3,370 filgrastim-ref; mean ages 62.1 years and 64.7 years, respectively). After IPTW, there were 162 patients in the filgrastim-sndz cohort and 3,297 in the filgrastim-ref cohort (mean age 64.5 years for both). FN incidence in the weighted filgrastim-sndz versus filgrastim-ref cohorts, respectively, was 1.4% versus 0.9% for N/F, 2.3% versus 1.7% for N/I, and 0.0% versus 0.3% for N/I/F; FN incidence was statistically equivalent between treatment cohorts. Among patients in either treatment cohort who developed FN, the proportion with FN-related inpatient stays during the first chemotherapy cycle ranged from 35.0% for N/I to 70.0% for N/I/F. Mean (SD) FN-related total medical costs across all patients who developed FN were $11,977 ($18,383) for N/F, $8,040 ($14,809) for N/I, and $21,733 ($30,003) for N/I/F, in 2015 U.S. dollars. For all 3 definitions of FN, the largest proportions (73.5%-93.4%) of medical costs were inpatient related.
CONCLUSIONS:
In this real-world study of patients with nonmyeloid cancers undergoing chemotherapy, the incidence of FN was statistically equivalent between individuals treated with filgrastim-sndz versus filgrastim-ref during their first chemotherapy cycle. FN-related health care resource utilization and medical costs among patients who developed FN were substantial.
DISCLOSURES:
This work was funded by Sandoz, which participated in the study design, data interpretation, writing and revision of the manuscript, and decision to submit the manuscript for publication. Balu and Campbell are employees of Sandoz, which is the manufacturer of the filgrastim biosimilars Zarzio and Zarxio. DeLeon was an employee of Sandoz at the time this study was conducted. Lal, Brekke, Elliott, and Korrer are employees of Optum, which was contracted by Sandoz to conduct this study.
