Background
Low‐molecular‐weight heparin is the guideline‐endorsed treatment for cancer‐associated venous thromboembolism (VTE). While apixaban is approved for the treatment of acute VTE, limited data ...support its use in cancer patients.
Objectives
The primary outcome was major bleeding. Secondary outcomes included VTE recurrence and a composite of major plus clinically relevant non‐major bleeding (CRNMB).
Patients/Methods
Patients with cancer‐associated VTE were randomly assigned to receive either apixaban 10 mg twice daily for seven days followed by 5 mg twice daily for six months or subcutaneous dalteparin (200 IU/kg for one month followed by 150 IU/kg once daily).
Results
Of 300 patients randomized, 287 were included in the primary analysis. Metastatic disease was present in 66% of subjects; 74% were receiving concurrent chemotherapy. Major bleeding occurred in 0% of 145 patients receiving apixaban, compared with 1.4% of 142 patients receiving dalteparin P = .138; hazard ratio (HR) not estimable because of 0 bleeding event in apixaban group. Recurrent VTE occurred in 0.7% of apixaban, compared to 6.3% of dalteparin patients HR 0.099, 95% confidence interval CI, 0.013‐0.780, P = .0281). Major bleeding or CRNMB rates were 6% for both groups.
Conclusions
Oral apixaban was associated with low major bleeding and VTE recurrence rates for the treatment of VTE in cancer patients.
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FZAB, GEOZS, GIS, IJS, IMTLJ, IZUM, KILJ, KISLJ, NLZOH, NUK, OILJ, PILJ, PNG, SAZU, SBCE, SBJE, SBMB, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Cancer is a disease of aging and, as the world's population ages, the number of older persons with cancer is increasing and will make up a growing share of the oncology population in virtually every ...country. Despite this, older patients remain vastly underrepresented in research that sets the standards for cancer treatments. Consequently, most of what we know about cancer therapeutics is based on clinical trials conducted in younger, healthier patients, and effective strategies to improve clinical trial participation of older adults with cancer remain sparse. For this systematic review, the authors evaluated published studies regarding barriers to participation and interventions to improve participation of older adults in cancer trials. The quality of the available evidence was low and, despite a literature describing multifaceted barriers, only one intervention study aimed to increase enrollment of older adults in trials. The findings starkly amplify the paucity of evidence‐based, effective strategies to improve participation of this underrepresented population in cancer trials. Within these limitations, the authors provide their opinion on how the current cancer research infrastructure must be modified to accommodate the needs of older patients. Several underused solutions are offered to expand clinical trials to include older adults with cancer. However, as currently constructed, these recommendations alone will not solve the evidence gap in geriatric oncology, and efforts are needed to meet older and frail adults where they are by expanding clinical trials designed specifically for this population and leveraging real‐world data.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SAZU, SBCE, SBMB, UL, UM, UPUK, VSZLJ
Background
Weight loss (WL) has been associated with shorter survival in patients with advanced cancer, while obesity has been associated with longer survival. Integrating body mass index (BMI) and ...WL provides a powerful prognostic tool but has not been well‐studied in lung cancer patients, particularly in the setting of clinical trials.
Methods
We analysed patient data (n = 10 128) from 63 National Cancer Institute sponsored advanced non‐small cell lung cancer (NSCLC) and small cell lung cancer (SCLC) trials. Risk matrices were created using BMI and WL percentage, which were divided into ‘grades’ based on median survival. Relationships between survival, BMI and WL percentage were examined using Kaplan–Meier estimators and Cox proportional hazards (PH) models with restricted cubic splines.
Results
For NSCLC, a twofold difference was noted in median survival between the BMI > 28 and WL ≤ 5% group (13.5 months) compared with the BMI < 20 and WL > 5% group (6.6 months). These associations were less pronounced in SCLC. Kaplan–Meier curves showed significant survival differences between grades for both NSCLC and SCLC (log‐rank, P < 0.0001). In Stage IV NSCLC, Cox PH analyses with restricted cubic splines demonstrated significant associations between BMI and survival in both WL ≤ 5% (P = 0.0004) and >5% (P = 0.0129) groups, as well as in WL > 5% in Stage III (P = 0.0306). In SCLC, these relationships were more complex.
Conclusions
BMI and WL have strong associations with overall survival in patients with advanced lung cancer, with a greater impact seen in NSCLC compared with SCLC. The integration of a BMI/WL grading scale may provide additional prognostic information and should be included in the evaluation of therapeutic interventions in future clinical trials in advanced lung cancer.
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FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SAZU, SBCE, SBMB, UL, UM, UPUK
Background
Cancer‐associated venous thromboembolism (VTE) carries a high rate of recurrence and death. Guidelines recommend continued anticoagulation therapy as long as active cancer persists. ...Apixaban 2.5 mg twice daily is the FDA‐approved dose for secondary prevention regardless of VTE causation. Whether this apixaban dose is appropriate for secondary VTE prevention in cancer patients is not clear. The rationale and design of this investigator initiated phase III, multicenter, randomized, double‐blind, trial assessing apixaban 2.5 mg vs 5 mg twice daily for 12 months for the secondary VTE prevention in cancer patients (n = 370) who have completed 6 months (but no more than 12 months) of anticoagulation is provided (NCT03080883).
Methods/Design
The primary study objective is to estimate differences in the combined rate of major plus clinically relevant non‐major bleeding for apixaban 2.5 mg vs 5 mg twice daily. Secondary efficacy outcome is to assess rates of venous or arterial thromboembolism. Participating centers are chosen from the Academic and Community Cancer Research United (ACCRU) consortium.
Conclusion
We anticipate these trial results to provide evidence supporting low‐dose apixaban as a safe agent for secondary prevention of cancer‐associated VTE for patients who have already completed 6‐12 months of anticoagulation.
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BFBNIB, DOBA, FZAB, GIS, IJS, IZUM, KILJ, NLZOH, NUK, OILJ, PILJ, PNG, SAZU, SBCE, SBMB, SIK, UILJ, UKNU, UL, UM, UPUK
Background
Risk‐stratified follow‐up guidelines that account for the absolute risk and timing of recurrence may improve the quality and efficiency of breast cancer follow‐up. The objective of this ...study was to assess the relationship of anatomic stage and receptor status with timing of the first recurrence for patients with local‐regional breast cancer and generate risk‐stratified follow‐up recommendations.
Methods
The authors conducted a secondary analysis of 8007 patients with stage I–III breast cancer who enrolled in nine Alliance legacy clinical trials from 1997 to 2013 (ClinicalTrials.gov identifier NCT02171078). Patients who received standard‐of‐care therapy were included. Patients who were missing stage or receptor status were excluded. The primary outcome was days from the earliest treatment start date to the date of first recurrence. The primary explanatory variable was anatomic stage. The analysis was stratified by receptor type. Cox proportional‐hazards regression models produced cumulative probabilities of recurrence. A dynamic programming algorithm approach was used to optimize the timing of follow‐up intervals based on the timing of recurrence events.
Results
The time to first recurrence varied significantly between receptor types (p < .0001). Within each receptor type, stage influenced the time to recurrence (p < .0001). The risk of recurrence was highest and occurred earliest for estrogen receptor (ER)‐negative/progesterone receptor (PR)‐negative/Her2neu‐negative tumors (stage III; 5‐year probability of recurrence, 45.5%). The risk of recurrence was lower for ER‐positive/PR‐positive/Her2neu‐positive tumors (stage III; 5‐year probability of recurrence, 15.3%), with recurrences distributed over time. Model‐generated follow‐up recommendations by stage and receptor type were created.
Conclusions
This study supports considering both anatomic stage and receptor status in follow‐up recommendations. The implementation of risk‐stratified guidelines based on these data has the potential to improve the quality and efficiency of follow‐up.
The time to first recurrence of breast cancer varied by receptor type and anatomic stage. The implementation of risk‐stratified guidelines based on data from this study has the potential to improve the quality and efficiency of follow‐up.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SAZU, SBCE, SBMB, UL, UM, UPUK
The commentary remarks on a recently published article on a study that examined predictors of poor outcomes in cancer patients using the SOFA score, answering to the question of whether the results ...of the study can completely inform decisions about terminal care management.
Background
Hand‐foot skin reaction (HFSR) is the most common regorafenib‐induced adverse event and is in need of effective prevention and palliation.
Materials and Methods
The Regorafenib Dose ...Optimization Study (ReDOS), a four‐arm, previously published trial with a 1:1:1:1 randomization scheme, was analyzed in a manner in keeping with the original protocol to assess whether clobetasol 0.05% cream (a corticosteroid) applied to the palms and soles twice per day for 8 weeks was more effective when prescribed preemptively (before the development of HFSR) versus reactively (after the development of HFSR). Patients were assessed during the first two cycles of regorafenib.
Results
Sixty‐one patients received preemptive clobetasol, and 55 received reactive clobetasol. Groups were balanced on demographics. Over the first two cycles, no evidence of HFSR occurred in 30% with preemptive clobetasol versus 13% with reactive clobetasol (p = .03). During the first cycle, 54% and 45% of patients had no HFSR with preemptive and reactive clobetasol, respectively (p = .35). During the second cycle, 33% and 15% had no HFSR with preemptive and reactive clobetasol, respectively (p = .02). During the second cycle, rates of grade 1, 2, and 3 HFSR were 30%, 8%, and 3%, respectively, with preemptive clobetasol and 43%, 18%, and 7%, respectively, with reactive clobetasol (p = .12). Patient‐reported outcomes showed HFSR compromised nearly all activities of daily living with worse quality of life in patients who received reactive versus preemptive clobetasol. No clobetasol‐induced adverse events were reported.
Conclusion
Preemptive clobetasol might lessen regorafenib‐induced hand‐foot reactions compared with reactive therapy. Further confirmatory studies are needed in a larger patient cohort.
Implications for Practice
Regorafenib causes hand‐foot skin reactions. Preemptive clobetasol, a high‐potency topical corticosteroid, appears to lessen the severity of this adverse event. Although further study is needed, the favorable adverse event profile of this intervention might prompt clinicians to discuss this option with their patients.
Hand‐foot skin reaction is a common regorafenib‐induced adverse event. This article reports on the use of topical clobetasol and its role when administered preventively, before a skin reaction occurs.
Objectives
To analyze self‐reported changes in physical function in older women with breast cancer receiving adjuvant chemotherapy.
Design
Secondary analysis of the Cancer and Leukemia Group B ...(CALGB) 49907 prospective randomized clinical trial.
Setting
CALGB institutions in the United States.
Participants
Women aged 65 and older with Stage I to III breast cancer enrolled in CALGB 49907 who had physical function data from before and after receipt of adjuvant chemotherapy (N=256; mean age 71.5, range 65–85).
Measurements
Participants were administered the physical function subscale of the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire before chemotherapy, at the end of chemotherapy, and 12 months after chemotherapy initiation. Functional decline was defined as a more than 10‐point decrease from baseline at each time point. Resilience was defined as return to within 10 points of baseline. Multivariable regression was used to examine pretreatment characteristics associated with physical function changes.
Results
Of 42% of participants who had physical function decline from before to the end of chemotherapy, 47% recovered by 12 months (were resilient). Almost one‐third experienced functional decline from before chemotherapy to 12 months later. Pretreatment fatigue was a risk factor for functional decline from before to the end of chemotherapy (P=.02). Risk factors for functional decline at 12 months included pretreatment dyspnea (P=.007) and being unmarried (P=.01).
Conclusion
Functional decline was common in older women receiving adjuvant chemotherapy for breast cancer in a clinical trial. Although half recovered their physical function, one‐third had a clinically meaningful decline at 12 months. Strategies are needed to prevent functional decline in older adults receiving chemotherapy. J Am Geriatr Soc 67:920–927, 2019.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SAZU, SBCE, SBMB, UL, UM, UPUK
Summary
Currently, low molecular weight heparin (LMWH) is the guideline endorsed treatment of patients with cancer associated venous thromboembolism (VTE). While apixaban is approved for the ...treatment of acute VTE, there are limited data supporting its use in cancer patients. The rationale and design of this investigator initiated Phase IV, multicenter, randomized, open label, superiority trial assessing the safety of apixaban versus dalteparin for cancer associated VTE is provided (ADAM-VTE; NCT02585713). The main aim of the ADAM-VTE trial is to test the hypothesis that apixaban is associated with a significantly lower rate of major bleeding compared to dalteparin in the treatment of cancer patients with acute VTE. The primary safety outcome is rate of major bleeding. Secondary efficacy objective is to assess the rates of recurrent VTE or arterial thromboembolism. Cancer patients with acute VTE (n=300) are randomized to receive apixaban (10 mg twice daily for 7 days followed by 5 mg twice daily thereafter) or dalteparin (200 IU/Kg daily for 30 days followed by 150 IU/kg daily thereafter) for 6 months. Stratification factors used for randomization include cancer stage and cancer specific risk of venous thromboembolism using the Khorana score. Participating centers are chosen from the Academic and Community Cancer Research United (ACCRU) consortium comprised of 90 oncology practices in the United States and Canada. Based on the hypothesis to be tested, we anticipate that these trial results will provide evidence supporting apixaban as an effective treatment of cancer associated VTE at lower rates of major bleeding compared to LMWH.
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