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This article describes a web‐based survey of the Alliance for Clinical Trials in Oncology membership, including physicians, nurses, patient advocates, project managers, statisticians, leadership, and administrative staff. The goal of the survey was to identify new strategies to effect change in accrual for older patients with cancer by eliciting the opinions of a national sample of the oncology clinical research workforce and patient advocates who participate in high‐impact cancer clinical research., Background. There are multiple known individual‐ and practice‐level barriers to enrollment of older patients with cancer to clinical trials, but little is known about how the clinical research workforce feels about potential higher‐level strategy changes aimed to promote increased enrollment of older patients. Subjects, Materials, and Methods. We invited all 11,351 Alliance for Clinical Trials in Oncology (“Alliance”) members to participate in an anonymous, web‐based survey to examine awareness of current accrual patterns for older patients to clinical trials, to ascertain consensus on how to tackle enrollment challenges, and to provide the impetus for high‐level changes to improve clinical trial accrual of older patients with cancer. Results. During the period from February 28, 2017, to June 16, 2017, 1,146 Alliance members participated (response rate = 10%), including a national diverse sample of physicians, nurses, administrative/clinical research staff, and patient advocates with representation from community, academic, and rural sites. Overall, one third felt that >50% of clinical trial enrollees should be age ≥65, and 64.9% felt the Alliance could improve upon enrollment of older patients. The four most commonly ranked strategies to improve enrollment of older patients were creating more dedicated trials for this population (36.3%), minimizing exclusion criteria focused on comorbidity (35.5%), developing independent strategies for those aged ≥65 and for those aged ≥70 (33.2%), and requiring that most/all Alliance trials have a specific expansion cohort of older patients (30.0%). Conclusion. We anticipate that the recommendations from >1,000 Alliance members will continue to propel important strategy changes aimed to improve accrual of older patients with cancer to clinical trials. Implications for Practice. This survey of the Alliance for Clinical Trials membership sought opinions on potential, large‐scale, national strategies to improve accrual of older adults with cancer. Consensus was found around multiple strategies, including creating more dedicated trials for older patients, developing less stringent eligibility criteria, and mandating expansion cohorts of older patients within broader Alliance trials. It is anticipated that the recommendations from >1,000 Alliance members will continue to propel important strategy changes aimed to improve accrual of older patients with cancer to clinical trials.

There remains a paucity of data regarding the use of potentially inappropriate medications (PIMs) in the supportive management of older adults undergoing chemotherapy. Raising awareness among healthcare providers regarding the frequency of their use and potential toxicities may help to minimize the risks to patients. The aim of this study was to evaluate the frequency of six specific classes of medications considered PIMs by the American Geriatrics Society Beers Criteria that are commonly included in the National Comprehensive Cancer Network (NCCN) chemotherapy order templates for hematologic malignancies. The six PIMs evaluated are first-generation antihistamines, benzodiazepines, corticosteroids, H2-receptor antagonists, metoclopramide, and antipsychotics. A total of 311 unique chemotherapy order templates published online by the NCCN for the treatment of hematologic malignancies were reviewed to determine the frequency that these six specific PIMs were recommended for supportive care. Approximately 45% of the NCCN chemotherapy templates for hematologic malignancies specifically recommended the use of at least one of the six PIMs examined. The remainder of the templates evaluated referred exclusively to the NCCN Guidelines® on Oncology for Antiemesis, which also included the use of at least one of the six PIMs evaluated. These findings demonstrate that PIMs are frequently used as supportive therapy in the treatment of hematologic malignancies. Increasing healthcare provider awareness of their potential side effects may minimize the risks associated with their use in older adults with hematologic malignancies undergoing chemotherapy.

OBJECTIVE: To evaluate how use of different reference populations affects estimates of breast cancer-related cognitive impairment rates. METHODS: Patients aged ≥60 years with stage 0–3 breast cancer (n = 371) and matched non-cancer controls (n = 370) completed 13 neuropsychological tests prior to systemic therapy or at enrollment (controls). The tests captured three domains: attention, processing speed and executive function; learning and memory; and visual-spatial function. Domain-specific impairment was defined as having one test score 2 SD below or two or more test scores 1.5 SD below the reference population means. Different reference populations were used to define impairment: published normative data, study-specific controls, age and education-stratified controls, and age and education-adjusted controls. The associations between the resultant impairment rates and breast cancer (vs. control) were evaluated using chi-square tests and logistic regression models. Cohen’s kappa coefficients were used to evaluate agreement of impairment rates between study-specific control performance and the other reference population groups. RESULTS: The patients and controls were aged 68.0 (SD 6.0) and 67.9 (SD 7.0) years, respectively. The association of breast cancer-control status with impairment did not differ based on reference group. Cognitive impairment based on published normative data yielded less agreement on impairment rates (κ = 0.22–0.89) than study-specific age and education-stratified control performance (κ = 0.62–1.00). CONCLUSION: The choice of reference populations did not affect conclusions about the association of cognition with breast cancer. However, while study-specific reference populations provided greater internal consistency in defining cognitive impairment, benchmarking against published normative data will enhance the ability to compare results across studies.

Background: Androgen receptor (AR) targeted therapy and immunotherapy represent one of the most promising strategies for metastatic triple negative breast cancer (mTNBC), which accounts for 15-20% of all breast cancers. As a nonsteroidal selective androgen receptor modulator (SARM), GTx-024 demonstrated preclinical activity in AR+ TNBC PDX model. Pembrolizumab is a highly selective humanized monoclonal antibody of the programmed cell death 1 receptor (PD-1). The complementary modes of action and low potential for overlapping toxicity make the combination promising in patients with AR+ mTNBC. Trial Design: This is an open-label Phase 2 study for AR+ mTNBC. Eligible participants receive pembrolizumab 200mg IV every 3 weeks in combination with GTx-024 18mg po daily. Eligibility Criteria: Eligible patients must have AR+ (>10%, 1+ by IHC) TNBC; failed up to 2 lines of therapy in metastatic setting; and have measurable disease per RECIST1.1. Patients are excluded if they have had prior checkpoint inhibitors or AR targeted agents. Patients with current or prior use of testosterone, testosterone-like agents, androgenic compounds, or anti-androgens (including systemic steroids and immunosuppressive medications)are excluded, as well as current or prior history of noninfectious pneumonitis requiring systemic steroid therapy. Specific Aims: The primary objective is to evaluate the safety/tolerability of GTx-024 and pembrolizumab and determine the response rate (CR or PR via RECIST 1.1) in patients with advanced AR+ TNBC. We will use clinical benefit rate (CBR), duration of response (DOR), PFS, and OS to test the efficacy of this novel drug combination. Statistical Design: A Simon's MiniMax two-stage Phase 2 design will be utilized. Based on the previously reported response rate associated with single agent pembrolizumab (19%), we consider a response rate of 19% for the combination as discouraging, and a 39% response rate as encouraging. As a result, we will initially accrue 15 patients (including 6 patients from safety lead-in treated at the tolerable dose). If 2 or fewer patients respond, we will stop accrual for futility. Otherwise, the study will accrue an additional 14 patients for a total of 29 patients. With 29 patients, if only 8 or fewer respond (≤27.6%), the study will be considered discouraging unless secondary evidence of clinical benefit is substantial. With more than 8 patients responding out of the 29 patients, the combination would be considered promising. This design has 85% power to declare a true response rate of 39% as promising (power), and a 10% probability of declaring a true 19% response rate as encouraging (type I error). The probability of early termination if the true response rate is 19% is 44%. Target Accrual: 29 Study Contact: Yuan Yuan MD PhD, City of Hope Comprehensive Cancer Center; Duarte, CA 91030; Email: yuyuan@coh.org Citation Format: Yuan Y, Frankel P, Synold T, Lee P, Yost S, Martinez N, Tang A, Mendez B, Schmolze D, Apple S, Hurria A, Waisman J, Somlo G, Tank N, Sedrak M, Mortimer J. A phase II clinical trial of the combination of pembrolizumab and selective androgen receptor modulator GTx-024 in patients with advanced androgen receptor positive triple negative breast cancer [abstract]. In: Proceedings of the 2017 San Antonio Breast Cancer Symposium; 2017 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2018;78(4 Suppl):Abstract nr OT1-05-02.

This abstract was not presented at the symposium.

This abstract was not presented at the symposium.

Background: Older adults are less likely to be included in clinical trials leading to the approval of novel cancer treatments. The Institute of Medicine and ASCO have identified therapeutic phase II trials as a key research priority to increase the evidence base for older adults with cancer. While targeted therapies may represent a less toxic option for older patients, few trials have studied their tolerability and efficacy in older adults. Here, we present a phase II study (NCT01273610) of the combination of trastuzumab and lapatinib in older patients with HER2+ metastatic breast cancer (MBC), incorporating geriatric oncology principles in the study design. Methods: Patients age ≥ 60 years with MBC and any number of prior chemotherapy (CT) lines received trastuzumab (either 4mg/kg loading dose followed by 2mg/kg weekly or 8mg/kg followed by 6mg/kg q/3 weeks) plus lapatinib 1000 mg/m2 daily in 21-day cycles. Patients completed a pre-treatment geriatric assessment including measures of function, comorbidity, cognition, nutrition, and psychosocial status. A toxicity risk score developed for older adults receiving cytotoxic CT was calculated for each patient (Hurria et al. JCO 2011 & 2016). Relationships between tolerability (dose reductions and grade (G) ≥ 3 toxicity attributed to treatment) and risk score analyzed using a log2 transformation were assessed using generalized linear models, Student's t tests, and Fisher's exact test. Response rate (RR) and progression free survival (PFS) were evaluated. Results: 40 patients (mean age 72 [60-92]) were accrued from 04/11 to 05/15. 25% (n = 10) were ≥ 75 years of age. 65% of patients (n = 26) had HR+ tumors and 35% (n = 14) were receiving ≥ 3rd line treatment. Median number of cycles was 4 (0-28). RR was 23% (n = 9, 95% CI 11-38%; 1 complete, 8 partial). 23% (n = 9) achieved stable disease. PFS was 2.7 months (95% CI 2.5-12). Based on the toxicity risk score, 21% (n = 8), 54% (n = 21), and 26% (n = 10) were at low, intermediate, and high risk. 70% (n = 28) of patients had G ≥ 2 toxicities and 20% (n = 8) G ≥ 3 toxicities. G 2 and 3 diarrhea occurred in 28% (n = 11) and 5% (n = 2) respectively. 5% (n = 2) were hospitalized due to treatment-related toxicity. No G ≥ 3 cardiac toxicities were observed. 23% of patients (n = 9) had treatment delays, and 43% (n = 17) required a lapatinib dose reduction. The mean toxicity risk score was higher in patients who required dose reductions (Student's t: p = 0.02). No statistically significant relationship was found between toxicity risk scores and the presence of G ≥ 3 treatment toxicity (logistic regression: OR = 3.08, 95% CI [0.54, 21.2], p = 0.22). Conclusions: Among older patients with MBC (79% at intermediate or high risk of G ≥ 3 cytotoxic CT toxicity), trastuzumab and lapatinib were well tolerated, with only 20% experiencing G3 toxicities. The toxicity risk score was not found to be significantly related with treatment toxicity, which may be explained by the very low incidence of G3 events. Patients with a low toxicity risk score were not likely to require a lapatinib dose reduction. Citation Format: O'Connor T, Soto-Perez-de-Celis E, Blanchard S, Chapman A, Kimmick G, Muss H, Luu T, Waisman JR, Li D, Mortimer J, Yuan Y, Somlo G, Stewart D, Katheria V, Levi A, Hurria A. Tolerability of the combination of lapatinib and trastuzumab in older patients with HER2 positive metastatic breast cancer [abstract]. In: Proceedings of the 2017 San Antonio Breast Cancer Symposium; 2017 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2018;78(4 Suppl):Abstract nr P5-21-08.

To translate promising preclinical data on the combination of vorinostat and ixabepilone for metastatic breast cancer (MBC) into clinical trials. We conducted a randomized two-arm Phase IB clinical trial of ascending doses of vorinostat and ixabepilone in prior -treated MBC patients. To determine the maximum tolerated dose (MTD), 37 patients were randomized to schedule A: every-3-week ixabepilone + vorinostat (days 1–14), or schedule B: weekly ixabepilone + vorinostat (days 1–7; 15–21) Pharmacokinetics were assessed. Nineteen additional patients were randomized to schedule A or B and objective response rate (ORR), clinical benefit rate (CBR), toxicity, progression-free survival (PFS), and overall survival (OS) were assessed. The schedule A MTD was vorinostat 300 mg daily (days 1–14), ixabepilone 32 mg/m2 (day 2); 21-day cycle 27% dose-limiting toxicities (DLTs). The schedule B MTD was vorinostat 300 mg daily (days 1–7; 15–21), ixabepilone 16 mg/m2 (days 2, 9, 16); 28-day cycle; no DLTs. Vorinostat and ixabepilone clearances were 194 L/h and 21.3 L/h/m2, respectively. Grade 3 peripheral sensory neuropathy was reported in 8% (A) and 21% (B) of patients. The ORR and CBR were 22 and 22% (A); 30 and 35% (B). Median PFS was 3.9 (A) and 3.7 (B) months. OS was 14.8 (A) and 17.1 (B) months. We established the MTD of vorinostat and ixabepilone. This drug combination offers a novel therapy for previously treated MBC patients. The potential for lower toxicity and comparable efficacy compared to current therapies warrants further study.

Purpose In the Study of (E7080) Lenvatinib in Differentiated Cancer of the Thyroid (SELECT), lenvatinib significantly prolonged progression-free survival (PFS) versus placebo in patients with radioiodine-refractory differentiated thyroid cancer (RR-DTC). This prespecified subanalysis investigated the effect of age on the efficacy and safety of lenvatinib. Patients and Methods This randomized, double-blind, phase III study enrolled patients with histologically confirmed RR-DTC stratified by age (≤ 65 or > 65 years). Patients (N = 392) received lenvatinib 24 mg/day (n = 261) or placebo (n = 131). The primary end point was PFS; secondary end points included overall survival (OS), objective response rate, and safety. Results In both treatment arms, median ages were 56 (younger group) and 71 years (older group). PFS benefit was maintained with lenvatinib versus placebo in the younger and older age groups, with median PFS of 20.2 versus 3.2 months (hazard ratio [HR], 0.19; 95% CI, 0.13 to 0.27; P < .001) and 16.7 versus 3.7 months (HR, 0.27; 95% CI, 0.17 to 0.43; P < .001), respectively. PFS did not differ with age in either treatment arm. OS was improved in older lenvatinib-treated patients versus placebo (HR, 0.53; 95% CI, 0.31 to 0.91; P = .020). Younger lenvatinib-treated patients showed significantly higher ORR (72% v 55%; P = .0038), longer time to first dose reduction (3.7 v 1.5 months), and lower proportion of grade ≥ 3 treatment-related adverse events (67% v 89%; P < .001) compared with older patients. Conclusion This subanalysis demonstrated improved PFS with lenvatinib treatment versus placebo in both age groups, although higher toxicity was observed in older patients. Despite the allowance of crossover after disease progression, the OS benefit was observed in older patients, suggesting that lenvatinib should be considered for treatment of patients of any age with RR-DTC.

Cancer‐related therapy is increasingly administered in the outpatient setting, resulting in increased dependence on caregivers suggest to provide physical and emotional support to patients. This article describes differences in patient versus caregiver assessments of patient health, considering caregiver perceptions of the patient's health and abilities compared to that reported by the patient., Background. As patients age, caregivers increasingly provide essential support and patient information. We sought to determine if patient‐caregiver assessments of patient health differ and if differences contribute to burden in caregivers of older adults with cancer. Materials and Methods. One hundred patients, aged ≥65, and their caregivers independently assessed patient function, comorbidity, nutrition, social activity, social support, and mental health. Caregivers completed the Caregiver Strain Index (CSI). Patient‐caregiver assessments were compared using the Wilcoxon signed rank test and paired t test. Association between caregiver burden and differences between patient‐caregiver assessments was examined using generalized linear regression. Results. Median patient age was 70 (range 65–91) and 70% had advanced disease. Sixty percent of patients reported requiring help with instrumental activities of daily living (IADLs); most had good social support (median Medical Outcomes Study [MOS]‐Social Support Survey score 92) and mental health (median Mental Health Inventory score 85). Caregivers were a median age of 66 (range 28–85), 73% female, 68% spousal caregivers, and 79% lived with the patient. Caregivers rated patients as having poorer physical function (more IADLs dependency [p = .008], lower Karnofsky Performance Status [p = .02], lower MOS‐Physical Function [p

BACKGROUND A nocebo is an inert substance associated with adverse events. Although previous studies have examined the positive (placebo) effects of such inert substances, few have examined negative (nocebo) adverse event profiles, particularly in older patients who have higher morbidity and can experience frequent and severe adverse events from cancer therapy. METHODS This study focused on placebo/nocebo-exposed patients who participated in 2 double-blind, placebo-controlled, cancer therapeutic studies, namely, North Central Cancer Therapy Group trial NCCTG 97-24-51 and American College of Surgeons Oncology Group trial Z9001, with the goal of reporting the comparative, age-based adverse event rates, as reported during the conduct of these trials. RESULTS Among the 446 patients who received only placebo/nocebo and who were the focus of the current report, 161 were aged ≥65 years at the time of respective trial entry, and 5234 adverse events occurred. Unadjusted adverse event rates did not differ significantly between patients aged ≥65 years and younger patients (rate ratio, 1.01; 99% confidence interval, 0.47-2.02), and the findings were similar findings for grade 2 or worse adverse events and for all symptom-driven adverse events (for example, pain, loss of appetite, anxiety). Adjustment for sex, ethnicity, baseline performance score, and individual trial resulted in no significant age-based differences in adverse event rates. Similar findings were observed with an age threshold of 70 years. CONCLUSIONS Adverse events are equally common in older and younger cancer patients who are exposed to nocebo and thus require the same degree of clinical consideration regardless of age. Cancer 2017;123:4193-4198. © 2017 American Cancer Society.

Background Rural women have limited access to breast cancer education, which partially contributes to late diagnosis and treatment. In this pilot study, we tested the feasibility of implementing a school-based breast cancer educational program for adolescents in a rural Mexican community. We hypothesized that the adolescents' knowledge on breast cancer would increase as a result of the program, and that there would be intergenerational transmission of that knowledge to their older female relatives. Materials and methods Female adolescents from a rural middle school received the educational program. The program would be considered feasible and acceptable if more than 75% reported being satisfied with its contents. Changes in knowledge in the students and their relatives were evaluated using baseline and 4 months follow-up questionnaires. Results One hundred twenty-six students were enrolled. The program was considered acceptable by 96% of the participants. The students' knowledge regarding breast cancer increased significantly from baseline to 4 months follow-up (63% to 82%). One hundred ninety-four female relatives completed the initial knowledge questionnaires. The relatives' knowledge regarding breast cancer showed a significant increase from baseline to 4 months follow-up (55% to 61%). Conclusion Implementing breast cancer educational programs for adolescents in rural communities is feasible and acceptable. The program increased the adolescents' knowledge on breast cancer, and promoted the intergenerational transmission of that knowledge to their female relatives. Intergenerational transmission of knowledge represents a potential method for providing population-based health awareness education globally. Implications for practice In limited-resource settings, education is a valuable tool for achieving early detection and downstaging of breast cancer. Unfortunately, rural women lack access to educational opportunities and information about breast cancer, which is a factor contributing to late diagnosis and treatment. In this study, we demonstrated that implementing a school-based breast cancer educational program for female adolescents in a rural Mexican community was feasible, acceptable, and increased their knowledge about breast cancer. Furthermore, the program encouraged the transmission of information to the students' older relatives. Intergenerational transmission of knowledge represents a novel and potentially effective tool in cancer education and promotion.

Breast cancer is a disease associated with aging. Before initiation of chemotherapy, an assessment of functional reserve is needed; however, simple performance assessment scores may not reflect the diverse nature of physical function and risk of toxicity among older adults. The focus of this article is on understanding the association between pre‐chemotherapy biomarkers (IL‐6, CRP, and D‐dimer) and measures of physical function., Background. Pro‐inflammatory and coagulation factors serve as biomarkers of aging and functional reserve. The purpose of this study was to determine if pro‐inflammatory (interleukin‐6 [IL‐6], C‐reactive protein [CRP]), and coagulation (D‐dimer) factors were associated with pre‐chemotherapy functional status in women with stage I–III breast cancer. Patients and Methods. Prior to chemotherapy initiation in patients with stage I–III breast cancer, the following was captured: IL‐6, CRP, D‐dimer blood levels, and physical function measures including activities of daily living (ADL, subscale of Medical Outcomes Study Physical Health); instrumental activities of daily living (IADL, subscale of the Older Americans Resources and Services Program); Timed Up and Go (TUG); physician‐rated Karnofsky Performance Status (KPS); and self‐rated KPS. The association of these biomarkers with physical function measures was evaluated. Results. One hundred sixty patients (mean age 58.3 years, range 30–81 years) with stage I–III breast cancer (stages I [n = 34; 21.5%], II [n = 88; 55.7%], III [n = 36; 22.8%]) were enrolled. The group with poorest physical function (defined by ADL

Although the field of frailty research has expanded rapidly, it is still a nascent concept within the clinical specialties. Frailty, conceptualized as increased vulnerability to stressors because of significant depletion of physiological reserves, predicts poorer outcomes in several medical specialties, including cardiology, HIV care, nephrology, and in the behavioral and social sciences. Incorporation of frailty assessment and frailty research into the specialties is hindered by a lack of a consensus definition, by the proliferation of measurement tools, inadequate understanding of the biology of frailty, and lack of validated clinical algorithms for patients who have frailty. In 2015, the American Geriatrics Society, the National Institute on Aging (NIA) and the Alliance for Academic Internal Medicine held a conference for awardees of the NIA sponsored ‘Grants for Early Medical/Surgical Specialists Transition into Aging Research (GEMSSTAR)’1 program to review the current state of the knowledge regarding frailty in the sub-specialties, as well as to highlight key examples of integrating frailty research into the medical specialties. Key research questions to advance frailty research into specialty medicine are proposed.

Purpose Despite increasing awareness of accrual challenges, it is unknown if accrual of older patients to breast cancer treatment trials is improving. Methods We examined accrual of older patients to Alliance for Clinical Trials in Oncology systemic therapy breast cancer trials during 1985-2012 and compared disease characteristics and reasons for therapy cessation for older (age ≥ 65 years and ≥ 70 years) versus younger (age < 65 years and < 70 years) participants. To examine accrual trends, we modeled age as a function of time, using logistic regression. Results Overall, 17% of study participants were ≥ 65 years of age. Approximately 15%, 24%, and 24% of participants in adjuvant, neoadjuvant, and metastatic trials were age ≥ 65 years, and 7%, 15%, and 13% were age ≥ 70 years, respectively. The odds of a patient age ≥ 65 years enrolling significantly increased over time for adjuvant trials (odds ratio [OR] per year, 1.04; 95% CI, 1.04 to 1.05) but decreased significantly for neoadjuvant and metastatic trials (OR, 0.62; 95% CI, 0.58 to 0.67 and OR, 0.98, 95% CI, 0.97 to 1.00). Similar trends were seen for those age ≥ 70 years but these were statistically significant for adjuvant and neoadjuvant trials only (OR, 1.05, 95% CI, 1.04 to 1.07; and OR, 0.57, 95% CI, 0.52 to 0.62). In general, those age ≥ 65 years ( v those < 65 years) in adjuvant studies had a higher mean number of lymph nodes involved and more hormone receptor-negative tumors, although tumor sizes were similar. Early protocol treatment cessation was also more frequent in those age ≥ 65 years (50%) versus < 65 years (35.9%) across trials. Conclusion Older patients with breast cancer remain largely underrepresented in cooperative group therapeutic trials. We observed some improvement in accrual to adjuvant trials but worsening of accrual for neoadjuvant/metastatic trials. Novel strategies to increase accrual of older patients are critical to meaningfully change the evidence base for this growing patient population.

BACKGROUND Objective, treatment‐independent markers of cancer‐related fatigue are needed to advance clinical trials. In the current study, the authors evaluated physical, neurocognitive, and serologic markers for correlation with self‐reported fatigue before and after (neo)adjuvant chemotherapy for patients with early‐stage breast cancer. METHODS Women with AJCC TNM Stage I‐III breast cancer consented to assessment before and after the completion of 4 cycles of dose‐dense doxorubicin and cyclophosphamide. Assessment included self‐reported fatigue (using the Brief Fatigue Inventory), depression (using the Center for Epidemiologic Studies–Depression Scale [CES‐D]), Pittsburgh Sleep Quality Index, and 28 objective measures (grip strength in dominant and nondominant hands, 6‐minute walk, daily total energy expenditure, 14 neurocognitive tests, and 10 serologic markers). Generalized linear regression models of fatigue were constructed (1 model per marker), and adjusted for depression, timing before/after chemotherapy, menopausal status, obesity, and educational level. P values were adjusted to control the False Discovery Rate. RESULTS Of 28 subjects, 3 withdrew without completing baseline assessments. Prechemotherapy and postchemotherapy data were available for the evaluation of physical measures (25 subjects aged 50.6 ± 9.5 years), neurocognitive tests (22 subjects), and serologic markers (10 subjects). On covariate‐adjusted analysis, interleukin (IL)‐12 was found to be associated with fatigue at both assessments (P, To identify objective measures of cancer‐related fatigue, herein the authors evaluate physical, neurocognitive, and serologic markers for correlation with the Brief Fatigue Inventory before and after (neo)adjuvant chemotherapy for patients with early‐stage breast cancer. Although several markers correlate with self‐reported fatigue at one assessment, only the cytokine interleukin 12 appears to correlate with fatigue both before and after chemotherapy.

Aging is the major risk factor for both the development of chronic diseases and loss of functional capacity. Geroscience provides links among the biology of aging, the biology of disease, and the physiology of frailty, three fields where enormous progress has been made in the last few decades. While, previously, the focus was on the role of aging in susceptibility to disease and disability, the other side of this relationship, which is the contribution of disease to aging, has been less explored at the molecular/cellular level. Indeed, the role of childhood or early adulthood exposure to chronic disease and/or treatment on accelerating aging phenotypes is well known in epidemiology, but the biological basis is poorly understood. A recent summit co-organized by the National Institutes of Health GeroScience Interest Group and the New York Academy of Sciences explored these relationships, using three chronic diseases as examples: cancer, HIV/AIDS, and diabetes. The epidemiological literature clearly indicates that early exposure to any of these diseases and/or their treatments results in an acceleration of the appearance of aging phenotypes, including loss of functional capacity and accelerated appearance of clinical symptoms of aging-related diseases not obviously related to the earlier event. The discussions at the summit focused on the molecular and cellular relationships between each of these diseases and the recently defined molecular and cellular pillars of aging. Two major conclusions from the meeting include the desire to refine an operational definition of aging and to concomitantly develop biomarkers of aging, in order to move from chronological to physiological age. The discussion also opened a dialogue on the possibility of improving late-life outcomes in patients affected by chronic disease by including age-delaying modalities along with the standard care for the disease in question.

We examined acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS) events among 9679 women treated for breast cancer on four adjuvant Alliance for Clinical Trials in Oncology trials with >90 months of follow-up in order to better characterize the risk for AML/MDS in older patients receiving anthracyclines. We used multivariable Cox regression to examine factors associated with AML/MDS, adjusting for age (≥65 vs.

Objective Older adults with cancer are at higher risk for costly and potentially dangerous hospital readmissions. Identifying risk factors for readmission in this population is important for future prevention of readmission. Materials and methods Hospital discharges among patients ≥ 65 years with solid tumors on non-surgical services from 2006-2011 were reviewed in this matched case-control study. We abstracted patient/cancer characteristics; functional status; fall risk; chemotherapy line; comorbidities; laboratory values; discharge parameters; and miscellaneous information (Do Not Resuscitate Order, pain scores) from medical records. Conditional logistic regression was used for univariate and multivariable analysis. Results This analysis included 184 case-patients readmitted within 30 days after discharge from the index admission and 184 sex- and age-matched control-patients discharged from index admission within three months of the cases with no readmission. Cases and controls had no differences in terms of primary cancer type, treatment, and index admission reason. Cases were more likely to have abnormal hemoglobin, albumin, sodium, and SGOT on discharge. Compared to those with ≤1 abnormal laboratory test, patients with 2 or more abnormal test results were 3 times more likely to be readmitted within 30 days. Conclusion This study demonstrated that older adults with cancer who had at least 2 abnormal laboratory results (hemoglobin, albumin, sodium, and SGOT) at discharge were 3 times more likely to be readmitted within 30 days compared to those with ≤1 abnormal results. These laboratory values may be predictive of the risk of readmission, and should be monitored before discharge to potentially prevent readmission.

PURPOSE Older women with breast cancer remain under-represented in clinical trials. The Cancer and Leukemia Group B 49907 trial focused on women age 65 years and older. We previously reported the primary analysis after a median follow-up of 2.4 years. Standard adjuvant chemotherapy showed significant improvements in recurrence-free survival (RFS) and overall survival compared with capecitabine. We now update results at a median follow-up of 11.4 years. PATIENTS AND METHODS Patients age 65 years or older with early breast cancer were randomly assigned to either standard adjuvant chemotherapy (physician’s choice of either cyclophosphamide, methotrexate, and fluorouracil or cyclophosphamide and doxorubicin) or capecitabine. An adaptive Bayesian design was used to determine sample size and test noninferiority of capecitabine. The primary end point was RFS. RESULTS The design stopped accrual with 633 patients at its first sample size assessment. RFS remains significantly longer for patients treated with standard chemotherapy. At 10 years, in patients treated with standard chemotherapy versus capecitabine, the RFS rates were 56% and 50%, respectively (hazard ratio [HR], 0.80; P = .03); breast cancer–specific survival rates were 88% and 82%, respectively (HR, 0.62; P = .03); and overall survival rates were 62% and 56%, respectively (HR, 0.84; P = .16). With longer follow-up, standard chemotherapy remains superior to capecitabine among hormone receptor–negative patients (HR, 0.66; P = .02), but not among hormone receptor–positive patients (HR, 0.89; P = .43). Overall, 43.9% of patients have died (13.1% from breast cancer, 16.4% from causes other than breast cancer, and 14.1% from unknown causes). Second nonbreast cancers occurred in 14.1% of patients. CONCLUSION With longer follow-up, RFS remains superior for standard adjuvant chemotherapy versus capecitabine, especially in patients with hormone receptor–negative disease. Competing risks in this older population dilute overall survival benefits.

Background Nutritional status can directly affect morbidity and mortality in older adults with cancer. This study evaluated the association between pretreatment body mass index (BMI), albumin level, and unintentional weight loss (UWL) in the prior 6 months and chemotherapy toxicity among older adults with solid tumors. Methods This was a secondary analysis of a prospective, multicenter study involving chemotherapy-treated patients 65 years old or older. Geriatric assessment, BMI, albumin level, and UWL data were collected before treatment. Multivariable logistic regression models evaluated the associations between nutritional factors and the risk of grade 3 or higher (grade 3+) chemotherapy toxicity. Results Seven hundred fifty patients with a median age of 72 years (range, 65-94 years) and mostly stage IV disease were enrolled. The median pretreatment BMI and albumin values were 26 kg/m2 (range, 15.1-52.1 kg/m2 ) and 3.9 mg/dL (range, 1.0-5.0 mg/dL), respectively. Nearly 50% of the patients reported UWL, with 17.6% reporting >10% UWL. Multivariable analysis revealed no association between >10% UWL and a risk for grade 3+ chemotherapy toxicity (adjusted odds ratio [AOR], 0.87; P = .58). Multivariable analysis showed a trend toward an association between a BMI ≥ 30 kg/m2 and a decreased risk of grade 3+ chemotherapy toxicity (AOR, 0.65; P = .06), whereas a low albumin level (≤3.6 mg/dL) was associated with a higher risk of grade 3+ chemotherapy toxicity (AOR, 1.50; P = .03). An analysis of the joint effect of BMI and albumin demonstrated the lowest risk of grade 3+ chemotherapy toxicity among patients with high BMIs (≥30 kg/m2 ) and normal albumin levels (AOR, 0.41; P = .008). Conclusions Among older adults with solid tumors, higher BMIs and normal albumin levels are associated with a lower risk of grade 3+ chemotherapy toxicity. Additional research is warranted to define the clinical significance of nutritional markers and to inform future interventions.

The preferred post-remission therapy for older patients with acute myeloid leukemia (AML) in first complete remission (CR1) remains uncertain. In this retrospective, multicenter study, we compared the outcomes for older AML patients (age 60–77 years) receiving allogeneic hematopoietic cell transplantation (alloHCT) (n = 431) with those treated on prospective National Clinical Trials Network induction and nontransplantation chemotherapy (CT) consolidation trials (n = 211). AlloHCT patients were younger (median age: 64.2 versus 67.9 years, p

Objective Our goal was to identify pathogenic variants (PV) associated with germline cancer predisposition in an unselected cohort of older breast cancer survivors. Older patients with cancer may also be at higher risk for clonal hematopoiesis (CH) due to their age and chemotherapy exposure. Therefore, we also explored the prevalence of PVs suggestive of CH. Methods We evaluated 44 older adults (65 years or older) diagnosed with breast cancer who survived at least two years after diagnosis from a prospective study, compared to healthy controls over the age of 65 (n = 36). DNA extracted from blood samples and a multi-gene panel test was used to evaluate for common hereditary cancer predisposition and CH PVs. Fisher's exact test was used to compare PV rates between groups. Results Eight PVs in ATM, BRCA2 (x2), PALB2, RAD51D, BRIP1, and MUTYH (x2) were identified in 7 of 44 individuals with breast cancer (15.9%, 95% CI: 7–30%), whereas none were identified in healthy controls (p = .01). Results remained statistically significant after removal of MUTYH carriers (p = .045). PVs indicative of CH (ATM, NBN, and PPM1D [x2]) were identified in three of 27 individuals with breast cancer who received chemotherapy and in one healthy control. Conclusion Moderate-risk and later disease onset high-risk hereditary cancer predisposition PVs were statistically significantly enriched in our survivorship cohort compared to controls. Because age- and chemotherapy-related CH are more frequent in this population, care must be taken to differentiate potential CH PVs from germline cancer predisposition PVs.

Background Insulin resistance has been proposed as a mediator of the increased cancer incidence and mortality associated with obesity. However, prior studies included limited cancer deaths and had inconsistent findings. Therefore, we evaluated insulin resistance and cancer-specific and all-cause mortality in postmenopausal women participating in the Women’s Health Initiative (WHI). Methods Eligible were a subsample of 22 837 WHI participants aged 50–79 years enrolled at 40 US clinical centers from 1993 to 1998 who had baseline fasting glucose and insulin levels. Baseline insulin resistance was measured by the homeostasis model assessment of insulin resistance (HOMA-IR). Cancers were verified by central medical record review and deaths verified by medical record and death certificate review enhanced by National Death Index queries. Cox proportional hazards regression models were used to calculate adjusted hazard ratios (HRs) and 95% confidence intervals (CIs) for cancer-specific and all-cause mortality. All statistical tests were two-sided. Results During a median of 18.9 years of follow-up, 1820 cancer deaths and 7415 total deaths occurred. Higher HOMA-IR quartile was associated with higher cancer-specific mortality (Q4 vs Q1, HR = 1.26, 95% CI = 1.09 to 1.47; Ptrend = .003) and all-cause mortality (Q4 vs Q1, HR = 1.63, 95% CI = 1.51 to 1.76; Ptrend < .001). A sensitivity analysis for diabetes status did not change findings. Among women with body mass index less than 25 kg/m2, higher HOMA-IR quartile was associated with higher cancer mortality (Fine and Gray, P = .004). Conclusions High insulin resistance, as measured by HOMA-IR, identifies postmenopausal women at higher risk for cancer-specific and all-cause mortality who could potentially benefit from early intervention.

The risk of surgery, particularly for older cancer patients with serious, extensive comorbidities, can make this otherwise curative modality precarious. Leveraging data from the American College of Surgeons Oncology Group, this study sought to characterize age-based comparative demographics, adverse event rates, and study completion rates to define how best to conduct research in older cancer patients. This study relied on clinical data from 21 completed studies to assess whether older patients experienced more grade 3 or worse adverse events and were more likely to discontinue study participation prematurely than their younger counterparts. The study enrolled 12,367 patients. The median age was 60 years, and 36% of the patients were 65 years of age or older. Among 4008 patients with adverse event data, 1067 (27%) had experienced a grade 3 or worse event. The patients 65 years or older had higher rates of grade 3 or worse adverse events compared to younger patients [32% vs. 24%; odds ratio (OR), 1.5; 95% confidence interval (CI), 1.3–1.7; p

OBJECTIVES To evaluate the relationships between aging-related domains captured by geriatric assessment (GA) for older patients with advanced cancer and caregivers' emotional health and quality of life (QOL). DESIGN In this cross sectional study of baseline data from a nationwide investigation of older patients and their caregivers, patients completed a GA that included validated tests to evaluate eight domains of health (eg, function, cognition). SETTING Thirty-one community oncology practices throughout the United States. PARTICIPANTS Enrolled patients were aged 70 and older, had one or more GA domain impaired, and had an incurable solid tumor malignancy or lymphoma. Each could choose one caregiver to enroll. MEASUREMENTS Caregivers completed the Generalized Anxiety Disorder-7, Distress Thermometer, Patient Health Questionnaire-2 (depression), and Short Form Health Survey-12 (SF-12 for QOL). Separate multivariate linear or logistic regression models were used to examine the association of the number and type of patient GA impairments with caregiver outcomes, controlling for patient and caregiver covariates. RESULTS A total of 541 patients were enrolled, 414 with a caregiver. Almost half (43.5%) of the caregivers screened positive for distress, 24.4% for anxiety, and 18.9% for depression. Higher numbers of patient GA domain impairments were associated with caregiver depression (adjusted odds ratio [aOR] = 1.29; P

Through the National Institute on Aging's (NIA's) "Grants for Early Medical/Surgical Specialists" Transition to Aging Research (GEMSSTAR) U13 grant, the NIA and the American Geriatrics Society (AGS) developed three transdisciplinary research conferences with a focus on mentoring and leadership skills development. The NIA's GEMSSTAR program evolved from two earlier programs, the AGS' Dennis W. Jahnigen and the Association of Specialty Professors' T. Franklin Williams Career Development Scholars Awards. It supports the continued cultivation of the next generation of medical and surgical specialty researchers with an interest in aging research. The award requires both geriatrics and specialty mentoring and currently provides up to $150,000 a year in direct support to scholars. Additionally, the award requires that scholars have a professional development plan that is complementary to the GEMSSTAR award. The U13 conferences, focused on frailty, models of aging, and cognition, brought together GEMSSTAR scholars, former scholars, innovators, mentors, and leaders in aging research, the specialties, and geriatric medicine. This article describes the themes of each of the GEMSSTAR U13 conferences and highlights the lessons learned on mentoring, team science, aging research networks, and work-life balance. We plan to use these lessons to guide the support we provide to the growing group of emerging leaders who are poised to lead the transdisciplinary research network of the future. J Am Geriatr Soc 67:650-656, 2019.

BACKGROUND. Ensuring older patients with advanced cancer and their oncologists have similar beliefs about curability is important. We investigated discordance in beliefs about curability in patient‐oncologist and caregiver‐oncologist dyads. MATERIALS AND METHODS. We used baseline data from a cluster randomized trial assessing whether geriatric assessment improves communication and quality of life in older patients with advanced cancer and their caregivers. Patients were aged ≥70 years with incurable cancer from community oncology practices. Patients, caregivers, and oncologists were asked: “What do you believe are the chances the cancer will go away and never come back with treatment?” Options were 100%, >50%, 50/50

BACKGROUND: Ibrutinib has been approved by the Food and Drug Administration for the treatment of patients with untreated chronic lymphocytic leukemia (CLL) since 2016 but has not been compared with chemoimmunotherapy. We conducted a phase 3 trial to evaluate the efficacy of ibrutinib, either alone or in combination with rituximab, relative to chemoimmunotherapy. METHODS: Patients 65 years of age or older who had untreated CLL were randomly assigned to receive bendamustine plus rituximab, ibrutinib, or ibrutinib plus rituximab. The primary end point was progression-free survival. The Alliance Data and Safety Monitoring Board made the decision to release the data after the protocol-specified efficacy threshold had been met. RESULTS: A total of 183 patients were assigned to receive bendamustine plus rituximab, 182 to receive ibrutinib, and 182 to receive ibrutinib plus rituximab. Median progression-free survival was reached only with bendamustine plus rituximab. The estimated percentage of patients with progression-free survival at 2 years was 74% with bendamustine plus rituximab and was higher with ibrutinib alone (87%; hazard ratio for disease progression or death, 0.39; 95% confidence interval [CI], 0.26 to 0.58; P

Few older cancer patients are enrolled in cancer clinical trials. This article assesses whether the development and conduct of older‐patient‐specific trials is justified, comparing outcomes of patients enrolled in trials purposely designed for older cancer patients versus age‐unspecified trials., Background. Less than 3% of older patients with cancer are enrolled in clinical trials. To reverse this underrepresentation, we compared older patients enrolled with older‐patient‐specific trials, defined as those designed for older patients with cancer, with those enrolled in age‐unspecified trials. Materials and Methods. We focused on individual patient data from those ≥65 years (younger patients excluded) and included all Alliance phase III adjuvant breast cancer trials from 1985–2012. Results. Among 2,277 patients, 1,014 had been enrolled to older‐patient‐specific and 1,263 to age‐unspecified trials. The median age (range) in the older‐patient‐specific trials was 72 (65–89) years compared with 68 (65–84) years in the cohort of older patients in age‐unspecified trials; p < .0001. A greater percentage of patients 75 years or older had enrolled in older‐patient‐specific trials compared with the cohort of age‐unspecified trials: 26% versus 6% (p < .0001). Median overall survival (OS) was 12.8 years (95% confidence interval [CI], 11.9–13.7) and 13.5 years (95% CI, 12.9–14.1) for older‐patient‐specific and age‐unspecified trials, respectively. OS was comparable (hazard ratio [HR], 1.08; 95% CI, 0.92–1.28; p = .34; referent: age‐unspecified trials), after adjusting for age, estrogen receptor status, tumor size, and lymph node status. Similar findings were reached for recurrence‐free survival. A lower rate of grade 3–5 adverse events (hematologic and nonhematologic) was reported in older‐patient‐specific trials (43% vs. 58%; p < .0001). Sensitivity analysis with chemotherapy only trials and subset analysis, adjusted for performance score, yielded similar OS results. Conclusion. Older‐patient‐specific trials appear to address this underrepresentation of older patients with ostensibly comparable outcomes. Clinical trial identification numbers. NCT00003088 (CALGB 9741); NCT00024102 (CALGB 49907); NCT00068601 (CALGB 40401); NCT00005970 (NCCTG N9831) Implications for Practice. This work underscores the importance of clinical trials that focus on the recruitment of older patients with cancer.

BACKGROUND Frailty has been suggested as a construct for oncologists to consider in treating older cancer patients. Therefore, the authors assessed the potential of creating a deficit-accumulation frailty index (DAFI) from a largely self-administered comprehensive geriatric assessment (CGA). METHODS Five hundred patients aged ≥65 years underwent a CGA before receiving chemotherapy. A DAFI was constructed, resulting in a 51-item scale, and cutoff values were examined for patients in the robust/nonfrail (cutoff value, 0.0

Purpose An American Society of Clinical Oncology (ASCO) panel considered the Cancer Care Ontario (CCO) recommendations on the role of patient and disease factors in selecting adjuvant therapy for women with early-stage breast cancer for endorsement. Methods ASCO staff reviewed the CCO guideline for methodologic rigor, and an ASCO panel of content experts reviewed the content of the recommendations. CCO Recommendations For making decisions regarding adjuvant therapy, nodal status, tumor size, estrogen receptor (ER), progesterone receptor (PgR), human epidermal growth factor receptor 2 (HER2) status, tumor grade, and lymphovascular invasion are relevant; Oncotype DX score and Adjuvant! Online may be used as risk stratification tools; and age, menopausal status, and medical comorbidities should be considered. Chemotherapy should be considered for patients with positive lymph nodes, ER-negative disease, HER2-positive disease, Adjuvant! Online mortality greater than 10%, grade 3 lymph node–negative tumors (T > 5 mm), triple-negative (ER-negative, PgR-negative, HER2-negative) tumors, lymphovascular invasion positivity, or estimated distant relapse risk of greater than 15% at 10 years based on Oncotype DX recurrence score (RS). Chemotherapy may not be beneficial or required for small node-negative tumors (T < 5 mm) without high-risk features or for patients with HER2-negative, strongly ER-positive, and PgR-positive cancer with micrometastatic nodal disease, T less than 5 mm, or Oncotype DX RS with an estimated distant relapse risk of less than 15% at 10 years. ASCO Panel Conclusion The ASCO panel endorses the recommendations with minor suggested revisions and highlights three areas that warrant further consideration: tumor histology and adjuvant therapy recommendations, risk stratification tools and proposed Oncotype DX RS thresholds to guide decisions about chemotherapy, and patient factors in decision making.

Objective To examine the ability of three popular self-report measures of depression to assess depression in a geriatric cancer setting. Method Cancer patients 70 years or older and on active treatment completed the Geriatric Depression Scale-Short Form, the Hospital Anxiety and Depression Scale, and the Center for Epidemiological Studies Depression Scale—Revised, and were interviewed using the depression module of the Structured Clinical Interview for DSM disorders (SCID) as the ‘gold standard.’ Analyses included calculating internal consistency, ROC curves, and the sensitivity and specificity to detect major depression (MDD) or minor depression (i.e. subthreshold depression). Results In a sample of 201 cancer patients (85% White; 64% completed college degree or higher), all three of the self-report measures produced adequate internal consistency and predicted depression greater than chance. However, the published cutoff scores for detecting MDD produced inadequate sensitivity, suggesting these scores will miss as many as 33%–83% of geriatric cancer patients who are depressed. Revised cutoff scores were lower than published cutoff scores. Conclusion Although these measures produced good internal consistency and were better than chance at predicting depression in a geriatric cancer sample, the published cutoff scores for these measures did not perform well in predicting MDD nor minor depression. Of the three measures, the CES-D appeared to have the most utility. This data suggests that these popular screening measures may be inadequate for reliably identifying depression in a geriatric cancer population. Researchers and clinicians, therefore, should use caution when selecting depression measures for geriatric cancer patients and consider using the lower cut-off scores presented here. Copyright © 2016 John Wiley & Sons, Ltd.

In May 2015, the Cancer and Aging Research Group, in collaboration with the National Cancer Institute and the National Institute on Aging through a U13 grant, convened a conference to identify research priorities to help design and implement intervention studies to improve the quality of life and survivorship of older, frailer adults with cancer. Conference attendees included researchers with multidisciplinary expertise and advocates. It was concluded that future intervention trials for older adults with cancer should: 1) rigorously test interventions to prevent the decline of or improve health status, especially interventions focused on optimizing physical performance, nutritional status, and cognition while undergoing cancer treatment; 2) use standardized care plans based on geriatric assessment findings to guide targeted interventions; and 3) incorporate the principles of geriatrics into survivorship care plans. Also highlighted was the need to integrate the expertise of interdisciplinary team members into geriatric oncology research, improve funding mechanisms to support geriatric oncology research, and disseminate high-impact results to the research and clinical community. In conjunction with the 2 prior U13 meetings, this conference provided the framework for future research to improve the evidence base for the clinical care of older adults with cancer. Cancer 2016;122:2459-68. © 2016 American Cancer Society.

BACKGROUND The extent to which cancer exacerbates or creates new health conditions is a long-standing, unanswered question. The current prospective study examined the short-term impact of cancer on the functioning, development of, and worsening of age-related health conditions among older adults who develop cancer compared with age-matched controls. METHODS Surveillance, Epidemiology, and End Results registry data were linked with Medicare Health Outcomes Survey (MHOS) data. A total of 921 eligible cases were Medicare beneficiaries with diagnosis of breast, colorectal, lung, or prostate cancer made between their baseline and follow-up MHOS. Using propensity score matching, 4605 controls without cancer were matched from the MHOS. Analysis of covariance and logistic regression were used to examine changes in physical functioning, activities of daily living, age-related conditions, and exacerbation of preexisting conditions for cases compared with controls. RESULTS Cancer groups demonstrated greater declines in activities of daily living and physical function compared with controls (mean, -1.53 [standard error, 0.14]), with the greatest change noted for patients with lung cancer (mean, -6.72 [standard error, 0.94]). Having a cancer diagnosis increased the risk of depression but did not increase the odds of developing arthritis in the hand and/or hip, urinary incontinence (except for prostate cancer), or vision and/or hearing problems. Having a cancer diagnosis also did not exacerbate the severity of arthritis or foot neuropathy. CONCLUSIONS The findings of the current study suggest that cancer is a stronger driver for declines in physical functioning and an increased risk of depression in older adults. Interventions are needed to decrease these risks. Clinicians need to prepare patients and families for changes in functioning levels and interventions that limit the declines for older patients with cancer are needed. Cancer 2016;122:1946–53. © 2016 American Cancer Society.

Purpose CALGB 49907 showed the superiority of standard therapy, which included either cyclophosphamide/doxorubicin (AC) or cyclophosphamide/methotrexate/fluorouracil over single-agent capecitabine in the treatment of patients age ≥ 65 with early-stage breast cancer. The treatment allowed dosing adjustments of methotrexate and capecitabine for pretreatment renal function. The purpose of the current analysis was to assess the relationship between pretreatment renal function and five end points: toxicity, dose modification, therapy completion, relapse-free survival, and overall survival. Methods Pretreatment renal function was defined as creatinine clearance (CrCl) using the Cockcroft-Gault equation. Multivariable logistic and proportional hazards regression were used to model separately for each regimen the relationship between CrCl and the first three binary end points and the last two time-to-event end points, respectively, after adjusting for variables of prognostic importance. Results Six hundred nineteen assessable patients were analyzed. The incidence of stage III (moderate) or stage IV (severe) renal dysfunction was 72%, 64%, and 75% for treatment with cyclophosphamide/methotrexate/fluorouracil, AC, and capecitabine, respectively. There was no relationship for any regimen between pretreatment renal function and the five end points. For AC, as CrCl increased, the odds of nonhematologic toxicity decreased (P = .008), whereas for capecitabine, as CrCl increased, the odds of experiencing toxicity of any type also increased (P = .035). Patients with renal insufficiency who received dose modifications were not at increased risk for complications compared with those who did not have renal insufficiency and received a full dose. Conclusion Excluding from clinical trials patients with renal insufficiency but good performance status on the basis of concern of excessive hematologic toxicity or poor outcomes may not be justified with appropriate dosing modifications. Results should be considered in the design of clinical trials for older patients.

Background: Older adults represent 50% or more of all newly diagnosed cancer patients annually; these patients have multiple morbidities, complicating treatment decision-making.. Discussions about the risks and benefits of cancer treatments might be improved by having data on estimated all-cause survival. ePrognosis (http://eprognosis.ucsf.edu/carey2.php) is an online tool validated in older adults without cancer. We compared survival estimates using ePrognosis to observed survival in a population of women with early stage breast cancer who volunteered for cooperative group studies. Methods: Participants in CALGB 49907 (n=194) and 369901 (n=809) who were age 70+ were included (total n=1003). Both studies had comparable eligibility: primary, newly diagnosed, invasive, non-metastatic breast cancer. In 49907, eligibly also included PS 0-2; in 369901 there were no PS restrictions, but women who failed a screening cognitive exam were excluded. The Carey 2-year Index from ePrognosis was used to estimate all-cause 2-year survival, based on age, sex, and daily function. Function (needing help from another person to bath and shop for groceries, difficulty walking several blocks and pushing or pulling a heavy object) was derived from the EORTC QLC-30. The Carey index from ePrognosis generates scores from 1-10, with higher scores indicating higher probability of death. Kaplan-Meier methods were used to obtain point estimates and confidence intervals for the observed 2-yr survival. A two sided z-test was used to test the hypothesis that the observed survival rate is equivalent to the predicted survival rate. Results: At two years from study entry, 921 women were alive; 56 had died, and 26 were lost to follow-up/withdrawn. The population was, on average, 76 years old (SD 4.8), primarily white (89.3%), and the majority had hormone receptor positive tumors (79.4%). In our population, the Carey 2-years index predicated survival was not significantly different than observed rates in the 0-2 points and underestimated the survival rates for patients who had 3-6 points and 7-10 points. ePrognosis Prediction49907 & 369901 PatientsPointsPredicted Probability of SurvivalNNumber of DeathsObserved Probability of Overall Survival at 2 years (%, 95% CI)p-value0-295%5332595% (93-97%)0.7433-688%4272394% (92-96%) Conclusions: In this population of older women with breast cancer, using a few readily available data items, ePrognosis provided accurate survival estimates for women with a low probability of death (0-2 points) and underestimated all-cause survival in women with an increased probability of death (3-10 points). Further studies are needed to assess the validity of this tool in samples of cancer patients with higher risks of 2-year mortality. Extended follow-up to validate the tools in predicting 5- and 10-year all-cause and non-cancer mortality risk will further contribute to decision making in older patients. Citation Format: Kimmick G, Pitcher B, Mandelblatt J, Clapp J, Ballman K, Barginear M, Freedman R, Artz A, Klepin H, Lafky J, Hopkins J, Winer E, Hudis C, Muss H, Cohen H, Jatoi A, Hurria A. All-cause survival estimates compared to observed survival in older women with breast cancer in CALGB 49907 and 369901 (Alliance A151503). [abstract]. In: Proceedings of the Thirty-Eighth Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2015 Dec 8-12; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2016;76(4 Suppl):Abstract nr P6-09-10.

Background: Pathologic complete response (pCR) and residual cancer burden (RCB scores of 0 [pCR] or 1[near CR]) after neoadjuvant chemotherapy (NCT) may predict for improved survival (Symmans et al. J Clin Oncol 25:4414-22, 2007). We set out to test the pCR rate with an anthracycline-free regimen of carboplatin (carb) and nab-paclitaxel (nab) in patients (pts) with triple negative breast cancer (TNBC). Materials and Methods: Forty-nine pts with stages II-III BC were to receive carb (AUC 6) on day 1 of a 28 day cycle, and nab 80 mg/m2 weekly, for a total of 4 cycles. Core biopsies were performed prior to NCT. Blood procurement for circulating tumor cell (CTC) analysis using the CellSearch platform was carried out pre-treatment, mid-treatment, and at surgery. We set out to assess the predictive value of Mammaprint (poor vs. good), BluePrint (basal, vs. luminal, vs. HER2) molecular subtype as well as microarray RNA and miRNA profiling, for pCR. Responses were also dichotomized as complete or near complete response (Symmans RCB scores of 0-1) vs. suboptimal response (RCB score > 1). Results: The median age was 53 (28-75). Pts presented with clinical stages II (63%) and III (37%). So far, 38 of the 49 pts accrued between 2/2012 and 6/2015, have undergone surgery, 68% of whom underwent modified radical mastectomy. The pCR rate (breast and lymph nodes in CR) was 53%, and RCB 0 and 1 were seen in 68% of pts. Toxicites included grade ¾ anemia (45%), thrombocytopenia (13%) and neutropenia (53%,1 pt with neutropenic fever). Dose adjustments were needed in over 80% of pts. Grades 2 or 3 peripheral neuropathy were seen in 8% each, and grades 3-4 fatigue (13%), hypokalemia (3%), and hyponatremia (3%) were observed. The median number of CTCs (pre-NCT) observed in 7 CTC positive pts of the first 27 pts who completed surgery was 1 (0-7), and 2 of the 7 pts continued to have CTCs at the time of surgery (1 CTC each), while 2 pts without CTCs pre-NCT had CTCs (1 each) detected at surgery. The final pt enrolled is expected to complete surgery by 10/2015. Results of sequential CTC assessments, MammaPrint/Blueprint and RNA/miRNA analysis of pre- and post-treatment specimens and their correlation with pCR will be presented. Conclusion: The non-anthracycline-containing regimen of carb and nab-paclitaxel induced a high pCR rate in TNBC, in preliminary analysis. Ongoing profiling may allow for future subset-specific modification of this regimen to increase pCR across all molecular subtypes of TNBC. Citation Format: Somlo G, Chung S, Frankel P, Hurria A, Koehler S, Kruper L, Mortimer JE, Paz B, Robinson K, Taylor L, Vito C, Waisman J, Yeon C, Yim J, Yuan Y, Tong T. Phase II trial of neoadjuvant chemotherapy with carboplatin and nab-paclitaxel in patients with triple negative locally advanced and inflammatory breast cancer. [abstract]. In: Proceedings of the Thirty-Eighth Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2015 Dec 8-12; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2016;76(4 Suppl):Abstract nr P1-14-10.

Cancer is a disease of aging as older adults are much more likely to develop cancer compared with their younger counterparts. Understanding the biology of cancer and aging remains complex, and numerous theories regarding the relationship between the two have been proposed. Cancer treatment decisions in older patients are particularly challenging, because the evidence is scarce and the risk of toxicity increases with age. Determination of biologic age is essential due to heterogeneity of functional status, comorbidity, and physiologic reserves between patients of the same chronologic age.

Breast cancer is the most common cancer in women, with an incidence that rises dramatically with age. The average age at diagnosis of breast cancer is 61 years, and the majority of woman who die of breast cancer are age 65 years and older. Major improvements in public health and medical care have resulted in dramatic increases in longevity. The oldest old (those age 80 years and older) are a rapidly expanding group and now comprise 9 million members of the US population. The treatment of individuals who are age 80 years and older is complex and involves clearly defining the goals and value of treatment while also weighing risks, such as the potential effects of treatment on functional loss and quality of life. Limited evidence-based treatment guidelines exist for the caring of this older cohort of patients with breast cancer. Data from clinical trials that enroll primarily younger patients lack the information needed to estimate the likelihood of toxicities that can be life changing in older adults. Clinicians who make treatment recommendations should place the available evidence in the context of the patient’s life expectancy and geriatric assessment results that include an evaluation of a patient’s functional status, comorbidities, cognition, social support, nutritional status, and psychological state. Furthermore, these decisions should be placed in the context of the patient’s goals for treatment, preferences, and values. This review summarizes the current literature and focuses on the role of geriatric assessment in treatment recommendations for patients age 80 years and older with early and metastatic breast cancer.

Answer questions and earn CME/CNE The purpose of the American Cancer Society/American Society of Clinical Oncology Breast Cancer Survivorship Care Guideline is to provide recommendations to assist primary care and other clinicians in the care of female adult survivors of breast cancer. A systematic review of the literature was conducted using PubMed through April 2015. A multidisciplinary expert workgroup with expertise in primary care, gynecology, surgical oncology, medical oncology, radiation oncology, and nursing was formed and tasked with drafting the Breast Cancer Survivorship Care Guideline. A total of 1073 articles met inclusion criteria; and, after full text review, 237 were included as the evidence base. Patients should undergo regular surveillance for breast cancer recurrence, including evaluation with a cancer-related history and physical examination, and should be screened for new primary breast cancer. Data do not support performing routine laboratory tests or imaging tests in asymptomatic patients to evaluate for breast cancer recurrence. Primary care clinicians should counsel patients about the importance of maintaining a healthy lifestyle, monitor for post-treatment symptoms that can adversely affect quality of life, and monitor for adherence to endocrine therapy. Recommendations provided in this guideline are based on current evidence in the literature and expert consensus opinion. Most of the evidence is not sufficient to warrant a strong evidence-based recommendation. Recommendations on surveillance for breast cancer recurrence, screening for second primary cancers, assessment and management of physical and psychosocial long-term and late effects of breast cancer and its treatment, health promotion, and care coordination/practice implications are made.

The American Society of Clinical Oncology (ASCO) convened a subcommittee to develop recommendations on improving the evidence base for treating older adults with cancer in response to a critical need identified by the Institute of Medicine. Older adults experience the majority of cancer diagnoses and deaths and make up the majority of cancer survivors. Older adults are also the fastest growing segment of the US population. However, the evidence base for treating this population is sparse, because older adults are underrepresented in clinical trials, and trials designed specifically for older adults are rare. The result is that clinicians have less evidence on how to treat older adults, who represent the majority of patients with cancer. Clinicians and patients are forced to extrapolate from trials conducted in younger, healthier populations when developing treatment plans. This has created a dearth of knowledge regarding the risk of toxicity in the average older patient and about key end points of importance to older adults. ASCO makes five recommendations to improve evidence generation in this population: (1) Use clinical trials to improve the evidence base for treating older adults with cancer, (2) leverage research designs and infrastructure for generating evidence on older adults with cancer, (3) increase US Food and Drug Administration authority to incentivize and require research involving older adults with cancer, (4) increase clinicians' recruitment of older adults with cancer to clinical trials, and (5) use journal policies to improve researchers' reporting on the age distribution and health risk profiles of research participants.

52 Background: Older adults with cancer often have age-associated vulnerabilities and challenges, especially during hospitalization. Geriatric assessment (GA) can help identify such vulnerabilities, generate recommendations, and guide the choice of interventions. Recently, GA-driven interventions have been shown to decrease chemotherapy toxicity among older adults with cancer in the outpatient setting. However, few studies have examined its role in the inpatient setting. Our purpose was to evaluate the feasibility of GA-driven interventions among hospitalized older adults with cancer. Methods: Hospitalized patients, age 75+, with a solid tumor malignancy were eligible. Each patient completed a GA while hospitalized at T1 (Timepoint 1) and one-month post discharge T2 (Timepoint 2). An Advanced Practice Nurse (APN) reviewed the T1 GA, provided targeted care utilizing GA results and implemented interventions based on predefined triggers built into the GA’s various domains. An APN also completed follow-up visits by phone at 1 week and 1 month post discharge. The primary outcome was feasibility, defined as the percentage of participants who received GA-guided interventions and was pre-specified as successful if > 80% were given recommendations. A secondary outcome of the study was to capture unplanned readmissions within 1 month post discharge. Results: Between 9/19/2017 and 5/3/2019, 49 patients were eligible and 40 were enrolled, an 82% participation rate. The median age was 80.5 years (range 75-88), 58% male, 63% Non-Hispanic white, 18% Hispanic, 15% Asian, 70% > a high school education, 73% married/partner, and 48% had stage IV cancer. Most common cancer types: GI (28%), GU (23%), lung (20%). All 40 patients (100%) had ≥ 1 predefined trigger in the GA generating interventions and completed ≥ 2 follow-up visits with the APN. In total, 857 interventions were recommended, and the mean number of interventions generated per patient was 11. The top 4 interventions were Occupational Therapy/Physical Therapy (n = 66), Social Work (n = 52), Nutrition (n = 39), and Pharmacy (n = 36). Overall 89% of GA-guided interventions were implemented. Unplanned hospital readmission was low with only one patient readmitted within 30 days (3%). Conclusions: Among hospitalized adults over age 75 with cancer, using GA to identify vulnerability, and provide GA-driven multidisciplinary interventions is feasible. Further studies are warranted to examine the impact of GA-driven interventions on outcomes among hospitalized older adults with cancer.

12010 Background: Geriatric assessment (GA) can predict chemotherapy (chemo) toxicity in older adults (age ≥65) with cancer. However, evidence regarding the effect of GA-driven intervention (GAIN) on the incidence of chemo toxicity has been limited. Therefore, we conducted a randomized controlled trial evaluating the impact of GAIN vs. standard of care (SOC) on chemo toxicity in older adults with cancer. Methods: Patients (pts) age ≥65, diagnosed with a solid malignancy, and starting a new chemo regimen at City of Hope were eligible (NCT02517034). In a 2:1 ratio, 600 pts were randomly assigned to either GAIN (n = 398) or SOC (n = 202) arms. All pts completed a baseline GA prior to chemo. In the GAIN arm, a multidisciplinary team led by a geriatric oncologist, nurse practitioner, social worker, physical/occupation therapist, nutritionist, and pharmacist, reviewed GA results and implemented interventions based on predefined triggers built into the GA’s various domains. In the SOC arm, GA results were sent to treating oncologists to use at their discretion. Pts were followed until either end of chemo or 6 months after start of chemo, whichever occurred first. The primary endpoint was incidence of grade 3-5 chemo-related toxicity (NCI CTCAE v.4.0). Secondary endpoints included advance directive (AD) completion, emergency room (ER) visits, hospitalizations, and average length of stay (ALOS). Chi-square and Fisher’s exact tests were used to compare the categorical outcomes, and Kruskal-Wallis test was used to compare the ALOS between arms. Results: Pt characteristics were balanced between arms. Median age was 71 (range 65-91). Cancer types included: 33% gastrointestinal, 23% breast, 16% lung, 15% genitourinary, and 13% other. Most (71%) had stage IV disease. The incidence of grade 3-5 chemo-related toxicity was 50.5% (95% CI: 45.6-55.4%) in the GAIN arm and 60.4% (95% CI: 53.7-67.1%) in the SOC arm (p = 0.02). Compared to SOC, the GAIN arm had a reduction of 9.9% (95% CI: 1.6-18.2%) in chemo-related toxicity. At the end of study, AD completion increased 24.1% in the GAIN arm vs. 10.4% in the SOC arm (p < 0.001). No significant differences in ER visits (27.4% vs. 30.7%), hospitalizations (22.1% vs. 19.3%), or ALOS (median 4.8 vs. 5.0 days) were observed between the GAIN and SOC arms, respectively. Conclusions: Integration of multidisciplinary GA-driven interventions reduced grade 3-5 chemo-related toxicity and improved AD completion in older adults with cancer. GA-driven interventions should be included as a part of cancer care for all older adults. Clinical trial information: NCT02517034 .

Background: Older adults with breast cancer receiving neo/adjuvant chemotherapy are at increased risk for toxicity and dose reductions, often leading to decreased relative dose intensity (dRDI < 85%) and potentially compromised chemotherapy benefits. Identifying which older patients are projected to have dRDI with standard regimens could help to optimize systemic treatment delivery and completion. Methods: We prospectively enrolled patients aged ≥ 65 who were starting neo/adjuvant chemotherapy for HER2-negative, stage I-III breast cancer. Geriatric assessment and clinical variables were captured at baseline. Chemotherapy regimen, dosing, and treatment-related modifications (reductions, delays, discontinuation) were also captured. RDI was calculated as the ratio of actual dose delivered to intended dose. Our primary outcome was dRDI, which we defined as RDI < 85% (associated with poorer survival, Bonadonna et al. NEJM 1995). Bivariate logistic regression for dRDI was performed to elucidate the relationship with baseline factors. Stepwise regression was used to identify the significant factors that are independently associated with dRDI. Results: Of 323 patients (median age 69, range 65-86), 216 had HR+/HER2- breast cancer and 107 had triple negative breast cancer (TNBC). Patients were treated with taxotere and cyclophosphamide [TC] (47%), anthracycline-based regimens (46%), and cyclophosphamide, methotrexate, and 5-fluorouracil [CMF] (7%). Overall, the mean RDI was 90.1% (median 100%, range 16.7%-100%), and 69 patients (21%) had dRDI (i.e. RDI 70, higher stage (II/III), use of non-TC regimens (anthracycline-based or CMF), abnormal liver function, KPS < 90, poor physical function, lack of social support, and cardiac conditions were associated with reduced RDI. Multivariate stepwise regression identified that anthracycline-based or CMF regimens (28% dRDI, OR=3.34, 95% CI 1.77-6.29), age >70 (27% dRDI, OR = 2.01, 95% CI 1.11-3.63), abnormal liver function (41% dRDI, OR = 2.50, 95% CI 1.10-5.66), and KPS < 90 (48% dRDI, OR = 4.31, 95% CI 2.06-9.03) were significantly associated with dRDI. dRDI was significantly associated with grade 3 or higher toxicities, hospitalization, dose reduction, dose delay, and early discontinuation of chemotherapy (all p < 0.001). Conclusion: Among older patients receiving neo/adjuvant chemotherapy for HER2-negative early-stage breast cancer, those aged > 70, treated with anthracycline or CMF regimens, with abnormal liver functions, and KPS < 90 were at substantially higher risk for reduced RDI (actual/planned dose) likely due to increased rates of toxicities, hospitalizations, dose modifications, and/or early treatment discontinuation. Future targeted supportive care interventions and/or alternative treatment regimens are needed to improve the delivery of chemotherapy in older patients who are predicted to have dRDI and better understand whether dRDI impacts outcomes in this population. Citation Format: Mina S Sedrak, Can-Lan Sun, Allison Magnuson, Hyman Muss, Rachel Freedman, Cary P Gross, William P Tew, Heidi Klepin, Tanya M Wildes, Efrat Dotan, Tracey O'Connor, Harvey J Cohen, Heeyoung Kim, Vani Katheria, Reena Jayani, Anait Arsenyan, Abrahm Levi, Kemeberly Charles, Arti Hurria, William Dale. Factors associated with decreased relative dose intensity in older adults with early-stage breast cancer receiving chemotherapy [abstract]. In: Proceedings of the 2019 San Antonio Breast Cancer Symposium; 2019 Dec 10-14; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2020;80(4 Suppl):Abstract nr PD10-10.