Andrew E. Chapman

Validation of a Prediction Tool for Chemotherapy Toxicity in Older Adults With Cancer

PURPOSE Older adults are at increased risk for chemotherapy toxicity, and standard oncology assessment measures cannot identify those at risk. A predictive model for chemotherapy toxicity was developed (N = 500) that consisted of geriatric assessment questions and other clinical variables. This study aims to externally validate this model in an independent cohort (N = 250). PATIENTS AND METHODS Patients age ≥ 65 years with a solid tumor, fluent in English, and who were scheduled to receive a new chemotherapy regimen were recruited from eight institutions. Risk of chemotherapy toxicity was calculated (low, medium, or high risk) on the basis of the prediction model before the start of chemotherapy. Chemotherapy-related toxicity was captured (grade 3 [hospitalization indicated], grade 4 [life threatening], and grade 5 [treatment-related death]). Validation of the prediction model was performed by calculating the area under the receiver-operating characteristic curve. RESULTS The study sample (N = 250) had a mean age of 73 years (range, 65 to 94 [standard deviation, 5.8]). More than one half of patients (58%) experienced grade ≥ 3 toxicity. Risk of toxicity increased with increasing risk score (36.7% low, 62.4% medium, 70.2% high risk; P < .001). The area under the curve of the receiver-operating characteristic curve was 0.65 (95% CI, 0.58 to 0.71), which was not statistically different from the development cohort (0.72; 95% CI, 0.68 to 0.77; P = .09). There was no association between Karnofsky Performance Status and chemotherapy toxicity (P = .25). CONCLUSION This study externally validated a chemotherapy toxicity predictive model for older adults with cancer. This predictive model should be considered when discussing the risks and benefits of chemotherapy with older adults.

Evaluation of a Pharmacist-Led Medication Assessment Used to Identify Prevalence of and Associations With Polypharmacy and Potentially Inappropriate Medication Use Among Ambulatory Senior Adults With Cancer

PURPOSE The use of multiple and/or inappropriate medications in seniors is a significant public health problem, and cancer treatment escalates its prevalence and complexity. Existing studies are limited by patient self-report and medical record extraction compared with a pharmacist-led comprehensive medication assessment. PATIENTS AND METHODS We retrospectively examined medication use in ambulatory senior adults with cancer to determine the prevalence of polypharmacy (PP) and potentially inappropriate medication (PIM) use and associated factors. PP was defined as concurrent use of five or more and less than 10 medications, and excessive polypharmacy (EPP) was defined as 10 or more medications. PIMs were categorized by 2012 Beers Criteria, Screening Tool of Older Persons Prescriptions (STOPP), and the Healthcare Effectiveness Data and Information Set (HEDIS). RESULTS A total of 248 patients received a geriatric oncology assessment between January 2011 and June 2013 (mean age was 79.9 years, 64% were women, 74% were white, and 87% had solid tumors). Only 234 patients (evaluated by pharmacists) were included in the final analysis. Mean number of medications used was 9.23. The prevalence of PP, EPP, and PIM use was 41% (n = 96), 43% (n = 101), and 51% (n = 119), respectively. 2012 Beers, STOPP, and HEDIS criteria classified 173 occurrences of PIMs, which were present in 40%, 38%, and 21% of patients, respectively. Associations with PIM use were PP (P < .001) and increased comorbidities (P = .005). CONCLUSION A pharmacist-led comprehensive medication assessment demonstrated a high prevalence of PP, EPP, and PIM use. Medication assessments that integrate both 2012 Beers and STOPP criteria and consider cancer diagnosis, prognosis, and cancer-related therapy are needed to optimize medication use in this population.

Development of a comprehensive multidisciplinary geriatric oncology center, the Thomas Jefferson University Experience.

BACKGROUND The proportion of older patients with cancer is expected to grow exponentially in the next two decades. This population has large heterogeneity and it is well known that chronologic age is a poor predictor of outcomes. Research has shown that these patients are best served with a Comprehensive Geriatric Assessment (CGA) to formulate individualized treatment plans for better outcomes. However, the best model for CGA has yet to be determined. MATERIALS AND METHODS Our objective was to develop a highly functional model for the establishment of a comprehensive multidisciplinary geriatric oncology center in the setting of a university based NCI-designated cancer center. Each patient is evaluated by medical oncology, geriatric medicine, pharmacy, social work and nutrition. Expert navigation is provided to enhance the patient experience. At the conclusion, the inter-professional team meets to review each case and formulate a comprehensive treatment plan. The patient is classified as Fit, Vulnerable, or Frail based on the complete CGA. RESULTS The average age of patients seen was 80.7 with the most common diagnoses being breast, colorectal and lung cancers. Twenty four percent of patients were determined to be Fit, 47% Vulnerable, and 29% Frail. Twenty one percent of patients determined to be Frail by CGA received an ECOG score of 0-1 by the oncologist. Our pharmacists made specific recommendations in over 75% of patients and social work provided assistance in over 50% of patients. CONCLUSIONS We were able to observe some interesting trends such as potential discordance with ECOG score and assessment of Fit/Vulnerable/Frail but due to limitations in the data, this paper is not able to illustrate definitive correlations. Several challenges with the development of the clinic include 1) patient related issues, 2) navigation, 3) financial reimbursement, 4) referral patterns, and 5) coordination of care during office hours. We feel that we have been able to establish a model for a comprehensive multidisciplinary geriatric oncology evaluation center in the setting of a university based cancer center.

Comorbidity in older adults with cancer

Comorbidity is an issue of growing importance due to changing demographics and the increasing number of adults over the age of 65 with cancer. The best approach to the clinical management and decision-making in older adults with comorbid conditions remains unclear. In May 2015, the Cancer and Aging Research Group, in collaboration with the National Cancer Institute and the National Institute on Aging, met to discuss the design and implementation of intervention studies in older adults with cancer. A presentation and discussion on comorbidity measurement, interventions, and future research was included. In this article, we discuss the relevance of comorbidities in cancer, examine the commonly used tools to measure comorbidity, and discuss the future direction of comorbidity research. Incorporating standardized comorbidity measurement, relaxing clinical trial eligibility criteria, and utilizing novel trial designs are critical to developing a larger and more generalizable evidence base to guide the management of these patients. Creating or adapting comorbidity management strategies for use in older adults with cancer is necessary to define optimal care for this growing population.

A pharmacist-led medication assessment used to determine a more precise estimation of the prevalence of complementary and alternative medication (CAM) use among ambulatory senior adults with cancer

OBJECTIVES The prevalence of complementary and alternative medication (CAM) use in senior adult oncology (SAO) patients is widely variable and little is known about whether polypharmacy (PP) and potentially inappropriate medication (PIM) use influences CAM use given the increased number of comorbidities and polypharmacy. One approach to optimize medication management is through utilization of pharmacists as part of a team-based, healthcare model. MATERIALS AND METHODS Prevalence of CAM and factors influencing CAM use was examined in a secondary analysis of 248 patients who received an initial comprehensive geriatric oncology assessment between January 2011 and June 2013. Data was collected from electronic medical records. CAM was defined as herbal medications, minerals, or other dietary supplements, excluding vitamins. Patient characteristics influencing CAM use (e.g. comorbidities, PP and PIM use) were analyzed. RESULTS Only 234 patients (evaluated by pharmacists) were included in the final analysis. Mean age was 79.9 years [range 61-98]; 64% women, 74% Caucasian, 87% with a solid tumor, mean comorbidities, 7.69. CAM prevalence was 26.5% (n=62) and median CAM use was 0 (range 0-10). The proportion of CAM use (1, 2, and 3) was 19.2%, 6.4%, and 0.4%, respectively. Associations with CAM use (versus no-CAM) were polypharmacy (P=0.045), vision impairment (P=0.048) and urologic comorbidities (P=0.021). CONCLUSIONS A pharmacist-led comprehensive medication assessment demonstrated a more precise estimation of CAM prevalence in the ambulatory SAO population. CAM use was associated with polypharmacy, ophthalmic and urologic medical conditions. Integrating pharmacists into team-based (geriatric and oncology) care models is an underutilized yet viable solution to optimize medication use.

Predictors of chemotherapy dose reduction at first cycle in patients age 65 years and older with solid tumors.

PURPOSE Age-based reduction of chemotherapy dose with the first cycle (primary dose reduction, PDR) is not routinely guideline recommended. Few studies, however, have evaluated how frequently PDR is utilized in the treatment of older patients with cancer and which factors may be associated with this decision. METHODS We conducted a secondary analysis of a multi-institutional prospective cohort study of patients age ≥65 years treated with chemotherapy. The dose and regimen were at the discretion of the treating oncologist. The prevalence of PDR and its association with treatment intent (palliative vs. curative), tumor type, patient characteristics (sociodemographics and geriatric assessment variables), and chemotherapy-associated toxicity were evaluated. RESULTS Among 500 patients (mean age 73, range 65-91 years), 179 patients received curative intent chemotherapy and 321 patients received palliative intent chemotherapy, with PDR being more common in the latter sub-group (15% vs. 25%, p = 0.005). Increasing age was independently associated with PDR in both sub-groups. Comorbidity (prior cancer or liver/kidney disease) was independently associated with PDR in the palliative sub-group alone while Karnofsky Performance Status (KPS) was not associated with PDR in either subgroup. There was no significant difference in the rates of grades 3-5 toxicity, dose reductions, or delays with PDR. Patients in the palliative sub-group treated with PDR had higher rates of hospitalization compared to those treated with standard doses. CONCLUSION PDR is more common in the palliative setting, but is also utilized among patients treated with curative intent. Factors associated with PDR include age and comorbid conditions, but not KPS.

Adjuvant chemotherapy with or without bevacizumab in patients with resected non-small-cell lung cancer (E1505): an open-label, multicentre, randomised, phase 3 trial

SUMMARY Background Adjuvant chemotherapy for resected early stage NSCLC provides modest survival benefit. Bevacizumab, a monoclonal antibody directed against vascular endothelial growth factor, improves outcomes when added to platinum-based chemotherapy in advanced stage non-squamous NSCLC. We conducted a phase III study to evaluate the addition of bevacizumab to adjuvant chemotherapy in early stage resected NSCLC (E1505). The primary endpoint was overall survival. Methods Adult patients (≥ 18 years old) with ECOG performance status 0 or 1 with completely resected stage IB (≥4 centimeters) to IIIA (AJCC 6th edition) NSCLC were enrolled within 6–12 weeks of surgery and stratified by chemotherapy regimen, stage, histology, and sex. Minimum mediastinal lymph node sampling at specified levels was required (level 7 and 4 for right-sided tumors or level 7 and 5 and/or 6 for left-sided tumors). Normal laboratory values within two weeks of randomisation were required for enrollment. Chemotherapy, which was selected for each patient prior to randomisation, consisted of four, 3-week (21-day) cycles of cisplatin (75 mg/m2 in all regimens) with either vinorelbine 30 mg/m2 days 1 and 8; docetaxel 75 mg/m2 day 1; OR gemcitabine 1200 mg/m2 days 1 and 8; OR, starting in 2009 with an amendment, pemetrexed 500 mg/m2 day 1 along with B12 and folic acid supplementation. Patients were randomised 1:1 to Arm A (chemotherapy) or Arm B, adding bevacizumab at 15 mg/kg every 3 weeks starting with cycle 1 of chemotherapy and continuing for one year. Randomisation to treatment arm was performed centrally and determined using permuted blocks within strata with dynamic balancing on institution. The study had 85% power to detect a 21% reduction in the overall survival (OS) hazard rate with a one-sided 0·025-level test. The primary endpoint was overall survival, which was defined as the time from randomisation to death from any cause, and patients who were thought to be alive at the time of final analysis were censored at the last date of contact with analysis done based on intention to treat. This is final analysis of the primary endpoint of overall survival of E1505 (NCT00324805). Findings From July 2007 to September 2013, 1501 patients were enrolled, of whom 26% (N=383) had stage IB, 44% (N=636) stage II, and 30% (N=439) stage IIIA) with 28% (N=422) squamous cell histology. Cisplatin-based chemotherapy regimens utilized were vinorelbine 25% (N=377), docetaxel 23% (N=343), gemcitabine 19% (N=283), and pemetrexed 33% (N=497). At a median follow-up time of 50·3 months (IQR 32.9–68.0), estimated OS hazard ratio (B/A) was 0·99 (95% CI: 0·82–1·19, p=0·90). The median OS on Arm A has not been reached and is 85.8 months (95% CI 74.9-NA) on Arm B. Statistically significantly increased grade 3–5 toxicities of note (all attributions) included: overall worst grade (ie all grade 3/4/5 toxicities) (67%(N=496) versus 83%(N=610)); hypertension (8%(N=60) versus 30%(N=219)), and neutropenia (33%(N=241) versus 37%(N=275)) on Arms A and B, respectively. There was no significant difference in grade 5 adverse events per arm (N=15 on arm A and N=19 on arm B). Interpretation The addition of bevacizumab to adjuvant chemotherapy failed to improve overall survival for patients with surgically resected early stage NSCLC. Bevacizumab does not have a role in this setting and should not be considered as an adjuvant therapy for resected NSCLC patients. Funding This study was coordinated by the ECOG-ACRIN Cancer Research Group and supported by the National Cancer Institute of the National Institutes of Health.

Randomized Phase II Trial of Irinotecan/Docetaxel or Irinotecan/Docetaxel Plus Cetuximab for Metastatic Pancreatic Cancer: An Eastern Cooperative Oncology Group Study.

Objectives:The primary objective was to determine the response rate in patients with metastatic pancreatic cancer treated in first line with irinotecan/docetaxel combination (Arm A) or with irinotecan/docetaxel/cetuximab combination (Arm B). Secondary endpoints were progression-free survival (PFS), overall survival (OS), toxicity, and the rate of thromboembolic events with prophylactic enoxaparin sodium. Patients and Methods:Patients were eligible who had measurable, metastatic adenocarcinoma of the pancreas, and normal bilirubin. All patients received anticoagulation. Docetaxel (35 mg/m2) and irinotecan (50 mg/m2) were administered once a week for 4 weeks followed by 2 weeks rest (Arm A) alone or with the addition of cetuximab (Arm B). The primary endpoint was response rate. Results:A total of 87 eligible patients were enrolled and treated. Grade 3/4 toxicity was observed in 74% of patients in Arm A and 76% in Arm B. The principal grade 3/4 toxicity was diarrhea. Response rates were 4.5% in Arm A and 7% in Arm B. Median PFS and OS were 3.9 and 6.5 months in Arm A and 4.5 and 5.4 months in Arm B. Conclusions:Docetaxel/irinotecan combination is associated with considerable toxicity. Objective responses were infrequent and addition of cetuximab in an unselected population was not beneficial, but PFS and OS were comparable with those achieved with other regimens. Docetaxel/irinotecan therapy is active in metastatic pancreatic cancer.

Patient-Centered Specialty Practice: Defining the Role of Specialists in Value-Based Health Care

&NA; Health care is at a crossroads and under pressure to add value by improving patient experience and health outcomes and reducing costs to the system. Efforts to improve the care model in primary care, such as the patient‐centered medical home, have enjoyed some success. However, primary care accounts for only a small portion of total health‐care spending, and there is a need for policies and frameworks to support high‐quality, cost‐efficient care in specialty practices of the medical neighborhood. The Patient‐Centered Specialty Practice (PCSP) model offers ambulatory‐based specialty practices one such framework, supported by a formal recognition program through the National Committee for Quality Assurance. The key elements of the PCSP model include processes to support timely access to referral requests, improved communication and coordination with patients and referring clinicians, reduced unnecessary and duplicative testing, and an emphasis on continuous measurement of quality, safety, and performance improvement for a population of patients. Evidence to support the model remains limited, and estimates of net costs and value to practices are not fully understood. The PCSP model holds promise for promoting value‐based health care in specialty practices. The continued development of appropriate incentives is required to ensure widespread adoption.

Hematology-Oncology Fellows’ Training in Geriatrics and Geriatric Oncology: Findings From an American Society of Clinical Oncology–Sponsored National Survey

PURPOSE Older adults compose the majority of patients with cancer in the United States; however, it is unclear how well geriatrics or geriatric oncology training is being incorporated into hematology-oncology (hem-onc) fellowships. METHODS A convenience sample of hem-onc fellows completed a (written or electronic) survey assessing their education, clinical experiences, and perceived proficiency in geriatric oncology during training; knowledge base in geriatric oncology; confidence in managing older adults with cancer; and general attitudes toward geriatric oncology principles. RESULTS Forty-five percent of respondents (N = 138) were female, 67% were based in the United States, and most (60%) were past their first year of training. Most fellows rated geriatric oncology as important or very important (84%); however, only 25% reported having access to a geriatric oncology clinic and more than one half (53%) reported no lectures in geriatric oncology. Fellows reported fewer educational experiences in geriatric oncology than in nongeriatric oncology. For example, among procedure-based activities, 12% learned how to perform a geriatric assessment but 78% learned how to perform a bone marrow biopsy ( P < .05). Of those completing the knowledge-based items, 41% were able to identify correctly the predictors of chemotherapy toxicity in older adults with cancer. CONCLUSION Despite the prevalence of cancer in older adults, hem-onc fellows report limited education in or exposure to geriatric oncology. The high value fellows place on geriatric oncology suggests that they would be receptive to additional training in this area.