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Background: Adherence and persistence studies face several methodologic difficulties, including short-term mortality. We compared approaches to quantify adherence and persistence to first line (1L) oral targeted therapy (TT) in patients diagnosed with metastatic renal cell carcinoma (mRCC). Methods: Patients with mRCC ages 66 years or more who initiated TTs within 4 months of diagnosis were identified in the Surveillance, Epidemiology, and End Results Medicare-linked database (2007–2015). Adherence [proportion of days covered (PDC) >80%] was calculated using (i) PDC with a fixed 6-month denominator including then excluding patients who died within the 6 months and (ii) PDC with a denominator measuring time on treatment. Risk of nonpersistence was obtained by censoring death or treating death as a competing risk using cumulative incidence functions. Results: Among 485 patients with mRCC initiating a 1L oral TT (sunitinib, 64%; pazopanib, 25%; other, 11%), 40% died within 6 months. Adherence was higher after restricting to patients who survived (60%) compared with including those patients and assigning zero days covered after death (47%). Risk of nonpersistence was higher when censoring patients at death, 0.91 [95% confidence interval (CI), 0.88–0.94], compared with treating death as a competing risk, 0.75 (95% CI, 0.71–0.79). Conclusions: Different approaches to handling death resulted in different adherence and persistence estimates in the metastatic setting. Future studies should explicitly report the proportion of patient deaths over time and explore appropriate methods to account for death as competing risk. Impact: Use of several approaches can provide a more comprehensive picture of medication-taking behavior in the metastatic setting where death is a major competing risk.

ObjectiveExamine the effect of tamoxifen and aromatase inhibitors (AIs) on the risk of 12 clinically relevant cardiovascular outcomes in postmenopausal female breast cancer survivors.MethodsWe carried out two prospective cohort studies among postmenopausal women with breast cancer in UK primary care and hospital data (2002–2016) and US Surveillance, Epidemiology and End Results-Medicare data (2008–2013). Using Cox adjusted proportional hazards models, we compared cardiovascular risks between AI and tamoxifen users; and in the USA, between users of both drug classes and women receiving no endocrine therapy.Results10 005 (UK) and 22 027 (USA) women with postmenopausal breast cancer were included. In both countries, there were higher coronary artery disease risks in AI compared with tamoxifen users (UK age-standardised incidence rate: 10.17 vs 7.51 per 1000 person-years, HR: 1.29, 95% CI 0.94 to 1.76; US age-standardised incidence rate: 36.82 vs 26.02 per 1000 person-years, HR: 1.29, 95% C I1.06 to 1.55). However, comparisons with those receiving no endocrine therapy (US data) showed no higher risk for either drug class and a lower risk in tamoxifen users (age-standardised incidence rate tamoxifen vs unexposed: 26.02 vs 35.19 per 1000 person-years, HR: 0.74, 95% 0.60 to 0.92; age-standardised incidence rate AI vs unexposed: 36.82 vs 35.19, HR: 0.96, 95% CI 0.83 to 1.10). Similar patterns were seen for other cardiovascular outcomes (arrhythmia, heart failure and valvular heart disease). As expected, there was more venous thromboembolism in tamoxifen compared with both AI users and those unexposed.ConclusionsHigher risks of several cardiovascular outcomes among AI compared with tamoxifen users appeared to be driven by protective effects of tamoxifen, rather than cardiotoxic effects of AIs.

Purpose Estimates of cancer therapy effects can differ in clinical trials and clinical practice, partly due to underrepresentation of certain patient subgroups in trials. We utilize a hybrid approach, combining clinical trial and real-world data, to estimate the comparative effectiveness of two adjuvant chemotherapy regimens for colon cancer. Methods We identified patients aged 66 and older enrolled in the Multicenter International Study of Oxaliplatin/5FU-LV in the Adjuvant Treatment of Colon Cancer. Similar patients were identified in the Surveillance, Epidemiology, and End Results (SEER)-Medicare database, initiating adjuvant chemotherapy with either 5-fluorouracil (5FU) alone or in combination with oxaliplatin (FOLFOX). We used logistic regression to estimate the likelihood of trial enrollment as a function of age, sex, and substage. Using inverse odds of sampling weights (IOSW), we compared 5-year mortality in patients randomized to FOLFOX vs 5FU using weighted Cox proportional hazards regression, the Nelson-Aalen estimator for cumulative hazards, and bootstrapping for 95% confidence intervals (CIs). Results There were 690 trial participants and 3834 SEER-Medicare patients. The SEER-Medicare population was older and had a higher proportion of stage IIIB and IIIC patients than the trial. After controlling for differences between populations, the IOSW 5-year HR was 1.21 (0.89, 1.65), slightly farther from the null than the trial estimate (HR = 1.14, 95%CI: 0.87, 1.49). Conclusions This study supports mounting evidence of little to no incremental reduction in 5-year mortality for FOLFOX vs 5FU in older adults with stage II-III colon cancer, emphasizing the importance of combining clinical trial and real-world data to support such conclusions.

BackgroundDespite the rapid approval of targeted therapies for metastatic renal cell carcinoma (mRCC) evidence on real world treatment patterns remains limited. This study evaluated patterns of first-line targeted therapy utilization and adherence in older adults, a population with a high burden of RCC. Methods2,093 patients aged ≥66 years with a primary diagnosis of mRCC were identified from United States (US)-based cancer registry and administrative claims data (2007-2015). We included only patients with de novo disease. We assessed the initiation of first-line targeted therapy within four months of diagnosis and persistence and adherence to targeted therapy, using the proportion of days covered (PDC). Multivariable logistic regression yielded adjusted odds ratios (ORs) and 95% confidence intervals (CIs) to describe characteristics associated with targeted therapy versus no targeted therapy initiation and for high (≥80% PDC) versus low adherence. Results 28.8% of patients received first-line targeted therapy within four months of diagnosis, with the proportion of patients receiving targeted therapy increasing over time. Older age (one-year increment OR:0.95 95%CI 0.93, 0.97), high comorbidity burden (OR:0.65 95%CI0.46, 0.93) and clear cell histology (OR:1.54 95%CI 1.19, 2.00) were associated with targeted therapy initiation. 48.2% of patients exhibited a high PDC to oral targeted therapy at 120 days, which was attenuated with inclusion of patients who died during the time period (34.2% PDC ≥80%). Conclusion Increasing age, high comorbidity burden and non-clear cell histology were associated with decreased targeted therapy initiation among patients with de novo mRCC. Our findings suggest adherence to oral therapies was low; future research exploring the mechanisms and impact of low adherence in this older patient population is warranted.

Background: The pharmacy reference database, Micromedex, lists concomitant hydrochlorothiazide and cyclophosphamide use as a potential, major drug–drug interaction (DDI), although only one small, single-center study supports this claim. Our objective was to estimate associations between this potential DDI and two adverse chemotherapy-related events, neutropenia-related hospitalizations and treatment regimen discontinuation, among a cohort of women with breast cancer initiating adjuvant chemotherapy containing cyclophosphamide. Methods: Using linked Surveillance, Epidemiology, and End Results Program (SEER)-Medicare data, we included women 66 years and older with breast cancer diagnosis between 2007 and 2011, who initiated a regimen containing cyclophosphamide. Risk ratios (RR) and 95% confidence intervals for adverse outcomes comparing women exposed versus unexposed to the potential DDI were assessed using modified multivariable Poisson regression adjusting for potential confounders. Results: In total, 27% of women receiving cyclophosphamide treatment were exposed to concomitant hydrochlorothiazide, of which 11% experienced a neutropenia-related hospitalization and 21% discontinued their chemotherapy regimen prior to completion. Adjusted risks of both adverse events were similar between those exposed and unexposed to the potential DDI [neutropenia-related hospitalization: adjusted RR (aRR) = 0.92 (0.70–1.21); treatment discontinuation: aRR = 1.00 (0.96–1.05)]. Conclusions: Our results do not support an association between concomitant hydrochlorothiazide use and two clinically relevant adverse chemotherapy-related events. Impact: Our results support reassessing and potentially lowering severity of this potential interaction in drug reference databases.

BACKGROUND: The quality of end-of-life (EOL) care in the USA remains suboptimal, with significant variations in care by race and across disease subgroups. Patient-provider communication may contribute to racial and disease-specific variations in EOL care outcomes. OBJECTIVE: We examined racial disparities in EOL care, by disease group (cancer vs. non-cancer), and assessed whether racial differences in patient-provider communication accounted for observed disparities. DESIGN: Retrospective cohort study using the 2001–2015 Surveillance, Epidemiology, and End Results - Consumer Assessment of Healthcare Providers and Systems data linked with Medicare claims (SEER-CAHPS). We employed stratified propensity score matching and modified Poisson regression analyses, adjusting for clinical and demographic characteristics PARTICIPANTS: Black and White Medicare beneficiaries 65 years or older with cancer (N=2000) or without cancer (N=11,524). MAIN MEASURES: End-of-life care measures included hospice use, inpatient hospitalizations, intensive care unit (ICU) stays, and emergency department (ED) visits, during the 90 days prior to death. KEY RESULTS: When considering all conditions together (cancer + non-cancer), Black beneficiaries were 26% less likely than their Whites counterparts to enroll in hospice (adjusted risk ratio [ARR]: 0.74, 95%CI: 0.66–0.83). Among beneficiaries without cancer, Black beneficiaries had a 32% lower likelihood of enrolling in hospice (ARR: 0.68, 95%CI: 0.59–0.79). There was no racial difference in hospice enrollment among cancer patients. Black beneficiaries were also at increased risk for ED use (ARR: 1.12, 95%CI: 1.01–1.26). Patient-provider communication did not explain racial disparities in hospice or ED use. There were no racial differences in hospitalizations or ICU admissions. CONCLUSION: We observed racial disparities in hospice use and ED visits in the 90 days prior to death among Medicare beneficiaries; however, hospice disparities were largely driven by patients without cancer. Condition-specific differences in palliative care integration at the end-of-life may partly account for variations in EOL care disparities across disease groups. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s11606-021-06778-6.

Background Outpatient diverticulitis is commonly treated with either a combination of metronidazole and a fluoroquinolone (metronidazole-with-fluoroquinolone) or amoxicillin-clavulanate alone. The U.S. Food and Drug Administration advised that fluoroquinolones be reserved for conditions with no alternative treatment options. The comparative effectiveness of metronidazole-with-fluoroquinolone versus amoxicillin-clavulanate for diverticulitis is uncertain. Objective To determine the effectiveness and harms of metronidazole-with-fluoroquinolone versus amoxicillin-clavulanate for outpatient diverticulitis. Design Active-comparator, new-user, retrospective cohort studies. Setting Nationwide population-based claims data on U.S. residents aged 18 to 64 years with private employer-sponsored insurance (2000 to 2018) or those aged 65 years or older with Medicare (2006 to 2015). Participants Immunocompetent adults with diverticulitis in the outpatient setting. Intervention Metronidazole-with-fluoroquinolone or amoxicillin-clavulanate. Measurements 1-year risks for inpatient admission, urgent surgery, and Clostridioides difficile infection (CDI) and 3-year risk for elective surgery. Results In MarketScan (IBM Watson Health), new users of metronidazole-with-fluoroquinolone (n = 106 361) and amoxicillin-clavulanate (n = 13 160) were identified. There were no differences in 1-year admission risk (risk difference, 0.1 percentage points [95% CI, -0.3 to 0.6]), 1-year urgent surgery risk (risk difference, 0.0 percentage points [CI, -0.1 to 0.1]), 3-year elective surgery risk (risk difference, 0.2 percentage points [CI, -0.3 to 0.7]), or 1-year CDI risk (risk difference, 0.0 percentage points [CI, -0.1 to 0.1]) between groups. In Medicare, new users of metronidazole-with-fluoroquinolone (n = 17 639) and amoxicillin-clavulanate (n = 2709) were identified. There were no differences in 1-year admission risk (risk difference, 0.1 percentage points [CI, -0.7 to 0.9]), 1-year urgent surgery risk (risk difference, -0.2 percentage points [CI, -0.6 to 0.1]), or 3-year elective surgery risk (risk difference, -0.3 percentage points [CI, -1.1 to 0.4]) between groups. The 1-year CDI risk was higher for metronidazole-with-fluoroquinolone than for amoxicillin-clavulanate (risk difference, 0.6 percentage points [CI, 0.2 to 1.0]). Limitation Residual confounding is possible, and not all harms associated with these antibiotics, most notably drug-induced liver injury, could be assessed. Conclusion Treating diverticulitis in the outpatient setting with amoxicillin-clavulanate may reduce the risk for fluoroquinolone-related harms without adversely affecting diverticulitis-specific outcomes. Primary funding source National Institutes of Health.

Estimates of cancer therapy effects can differ in clinical trials and clinical practice, partly due to underrepresentation of certain patient subgroups in trials. We utilize a hybrid approach, combining clinical trial and real-world data, to estimate the comparative effectiveness of two adjuvant chemotherapy regimens for colon cancer.We identified patients aged 66 and older enrolled in the Multicenter International Study of Oxaliplatin/5FU-LV in the Adjuvant Treatment of Colon Cancer. Similar patients were identified in the Surveillance, Epidemiology, and End Results (SEER)-Medicare database, initiating adjuvant chemotherapy with either 5-fluorouracil (5FU) alone or in combination with oxaliplatin (FOLFOX). We used logistic regression to estimate the likelihood of trial enrollment as a function of age, sex, and substage. Using inverse odds of sampling weights (IOSW), we compared 5-year mortality in patients randomized to FOLFOX vs 5FU using weighted Cox proportional hazards regression, the Nelson-Aalen estimator for cumulative hazards, and bootstrapping for 95% confidence intervals (CIs).There were 690 trial participants and 3834 SEER-Medicare patients. The SEER-Medicare population was older and had a higher proportion of stage IIIB and IIIC patients than the trial. After controlling for differences between populations, the IOSW 5-year HR was 1.21 (0.89, 1.65), slightly farther from the null than the trial estimate (HR = 1.14, 95%CI: 0.87, 1.49).This study supports mounting evidence of little to no incremental reduction in 5-year mortality for FOLFOX vs 5FU in older adults with stage II-III colon cancer, emphasizing the importance of combining clinical trial and real-world data to support such conclusions.

Purpose The combination of chemotherapy and trastuzumab is the standard of care for adjuvant treatment of human epidermal growth factor receptor 2–positive breast cancer. Two regimens have been widely adopted in the United States: doxorubicin, cyclophosphamide, paclitaxel, and trastuzumab (ACTH) and docetaxel, carboplatin, and trastuzumab (TCH). No head-to-head comparison of these regimens has been conducted in a clinical trial, and existing trial data have limited generalizability to older patients. Methods We used SEER-Medicare data from 2005 to 2013 to compare outcomes of ACTH versus TCH among patients age older than 65 years. Propensity score matching was used to balance cohort characteristics between treatment arms. Outcomes included toxicity-related hospitalization, survival, and trastuzumab completion. Data from 1,077 patients receiving ACTH or TCH were analyzed, and the propensity-matched subsample included 416 women. Results There was a significant shift toward TCH over time, with 88% of patients receiving ACTH in 2005 compared with 15% by 2011. Among propensity score–matched patients, we found no difference between regimens in health care use overall or for chemotherapy-related adverse events (ACTH, 34% v TCH, 36.5%; P = .46). Patients receiving TCH were significantly more likely to complete trastuzumab (89% v 77%; P = .001). There was no difference in 5-year breast cancer–specific survival (ACTH, 92% v TCH, 96%; hazard ratio, 2.08; 95% CI, 0.90 to 4.82) or overall survival. Conclusion Among a matched sample of older patients, ACTH compared with TCH was not associated with a higher rate of serious adverse events or hospitalizations, but it was associated with less completion of adjuvant trastuzumab. We did not detect a difference in 5-year survival outcomes for ACTH compared with TCH. In the context of limited evidence in older patients, selection between these two regimens on the basis of concerns about differential toxicity or efficacy may not be appropriate.

Purpose The incidence of treatment-related toxicity for adjuvant chemotherapy in breast cancer is well documented in clinical trials. However, the effect of chemotherapy on functional outcomes in older patients is less well known. We identified a cohort of older women diagnosed with early stage breast cancer to examine the association between exposure to chemotherapy and a claims-based measure of function-related adverse events (FAE). Methods Using the Surveillance, Epidemiology, and End Results (SEER)-Medicare dataset, we identified women aged ≥ 66 diagnosed with stage I or II breast cancer from 2004 to 2011. FAE were defined as one or more claims suggestive of functional impairment within 24 months following chemotherapy including claims for durable medical equipment and skilled care. Women who did not receive chemotherapy were weighted to reflect the covariate distribution of chemotherapy recipients using propensity score weighting for age, stage, baseline healthcare utilization, and comorbidities. Results The cohort included 44,626 patients, 6892 (15%) received chemotherapy. 19% of the population experienced ≥ 1 FAE. After propensity weighting, chemotherapy was associated with a small increased risk of FAEs (HR 1.12, 95% confidence interval: 1.04, 1.20). Results were similar in patients 75 years and older versus younger patients. In the chemotherapy group, the highest risk of FAE occurred in the first 3 months, but persisted through follow-up. Conclusions Exposure to chemotherapy was associated with a small increased risk of FAE which did not vary by age. These data can be used to inform treatment decision making for older patients with breast cancer who are eligible for adjuvant chemotherapy.

BACKGROUND: We aimed to examine the association between acute pancreatitis, a potential early symptom of pancreatic cancer, and pancreatic cancer stage, treatment, and prognosis.METHODS: We conducted a cohort study of patients diagnosed with pancreatic cancer during 2004-2017 using population-based registry data from Denmark and Surveillance, Epidemiology, and End Results (SEER) data linked with Medicare claims from the United States (US), which include individuals aged 65 + . We ascertained information on acute pancreatitis diagnoses up to 90 days before pancreatic cancer and followed them for a maximum of five years. We assessed overall survival difference at 30 days, six months, and one, three and five years, comparing patients with and without coexistence of acute pancreatitis. Secondary outcomes were cancer stage and treatment.RESULTS: We identified 12,522 Danish and 37,552 US patients with pancreatic cancer (median age 71 and 78 years, respectively). In the Danish cohort, 1.4 % had acute pancreatitis before pancreatic cancer vs. 5.9 % in the US cohort. After five years of follow-up, the survival difference was 6.1 % (95 % CI: [-0.4 %, 12.6 %]) in Danish and 1.7 % (95 % CI: [0.8 %, 2.7 %]) in US patients, comparing patients with and without acute pancreatitis. Patients with acute pancreatitis had lower prevalence of metastatic tumors at diagnosis (Denmark: 42.5 % vs. 48.7 %; US: 34.4 % vs. 45.9 %) and higher resection frequencies (Denmark: 20.1 % vs. 12.1 %; US: 16.1 % vs.11.3 %) than patients without acute pancreatitis.CONCLUSIONS: Pancreatic cancer patients with acute pancreatitis diagnosed up to 90 days before cancer diagnosis had earlier stage at diagnosis and better survival than patients without acute pancreatitis.

Background: It has been suggested that cardiovascular risks are increased in breast cancer survivors, but few studies have quantified the risks of a range of specific clinically important cardiovascular outcomes in detail. Patients and Methods: Women aged >65 years with incident breast cancer from 2004 to 2013 in the SEER-Medicare linked database were matched with 5 cancer-free female counterparts (5:1 ratio). Prevalence of specific cardiovascular outcomes at baseline was measured, then Cox regression was used to calculate hazard ratios (HRs) and 95% confidence intervals for the risk of individual cardiovascular outcomes during follow-up. Modification of the effect was investigated by time since diagnosis, race/ethnicity, prior cardiovascular disease (CVD), and age. Results: In all, 91,473 women with breast cancer and 454,197 without breast cancer were included. Women with breast cancer had lower baseline prevalence of all CVDs. Compared with cancer-free controls, breast cancer survivors had substantially increased risks of deep vein thrombosis (adjusted HR, 1.67; 95% CI, 1.62–1.73; 386,484 person-years of follow-up) and pericarditis (HR, 1.43; 95% CI, 1.38–1.49; 390,776 person-years of follow-up); evidence of smaller increased risks of sudden cardiac arrest, arrhythmia, heart failure, and valvular heart disease (adjusted HRs ranging from 1.05–1.09, lower CI limits all ≥1); and evidence of lower risk of incident angina, myocardial infarction, revascularization, peripheral vascular disease, and stroke (adjusted HRs ranging from 0.89–0.98, upper CI limits all ≤1). Increased risks of arrhythmia, heart failure, pericarditis, and deep vein thrombosis persisted >5 years after cancer diagnosis. Conclusions: Women with a history of breast cancer were at increased risk of several CVDs, persisting into survivorship. Monitoring and managing cardiovascular risk throughout the long-term follow-up of women diagnosed with breast cancer should be a priority.

ObjectiveExamine the effect of tamoxifen and aromatase inhibitors on 12 clinically relevant individual cardiovascular outcomes in postmenopausal female breast cancer survivors using large-scale datasets from the UK and US.DesignTwo prospective cohort studiesSettingPopulation-based using data from the UK Clinical Practice Datalink linked with Hospital Episode Statistics (2002-2016), and the US Surveillance, Epidemiology and End Results-Medicare database (2008-2013).Participants10005 and 22027 postmenopausal women with breast cancer in the UK and US respectively.ExposuresAromatase inhibitor compared with tamoxifen use; the US cohort additionally included a comparison with an “unexposed” group of women with oestrogen or progesterone receptor positive breast cancer but no endocrine therapy use.Outcomes12 clinically relevant individual cardiovascular outcomes (and two composite coronary and venous thromboembolic outcomes)ResultsIn both the UK and the US, there was evidence of an increased risk of coronary artery disease in aromatase inhibitor compared with tamoxifen users (UK incidence rate: 10.18 vs 6.87 per 1000 person-years, HR: 1.29, 0.94-1.76; US incidence rate: 35.26 vs 26.95 per 1000 person-years, HR: 1.29, 1.06-1.55), but the US data showed no increase in risk compared with the unexposed group (incidence rate for tamoxifen vs unexposed: 26.95 vs 38.70 per 1000 person-years, HR: 0.74, 0.60-0.92; incidence rate for aromatase inhibitors vs unexposed: 35.26 vs 28.70, HR: 0.96, 0.83-1.10). Similar patterns were seen for other cardiovascular outcomes such as arrhythmia, heart failure, and valvular heart disease. As expected, there were more venous thromboembolic events in tamoxifen users compared with both aromatase inhibitor users and those unexposed. There was a high degree of consistency between results in the two countries.ConclusionsIncreased risks of several cardiovascular diseases among aromatase inhibitor compared with tamoxifen users appeared to be driven by protective effects of tamoxifen, rather than toxic effects of aromatase inhibitors. We also confirmed the known increased risk of venous thromboembolic events in tamoxifen users.WHAT THIS PAPER ADDSWhat is already known on this topicIt is known that tamoxifen use increases venous thromboembolism risk, but evidence for other cardiovascular outcomes is less clear.Patterns of results are suggestive of a lower risk of coronary heart disease outcomes with tamoxifen compared to both aromatase inhibitor use and no tamoxifen or placebo, but cardiovascular events are often a secondary consideration and inconsistently reported in trials, and most observational studies use composite cardiovascular definitions, ignoring potentially differential effects on specific cardiovascular outcomes.What this study addsAmong postmenopausal women with breast cancer, we found an increased risk of several cardiovascular diseases in aromatase inhibitor compared with tamoxifen users across two countries, which appeared to be driven by protective effects of tamoxifen, rather than toxic effects of aromatase inhibitors. We also found the known increased venous thromboembolism risk in tamoxifen users.There was no evidence that aromatase inhibitors or tamoxifen increases cardiovascular disease risk, other than the known increased venous thromboembolism risk with tamoxifen use. However, there was an apparent protective effect of tamoxifen on other cardiovascular outcomes.

Background Academic physicians, such as those affiliated with National Cancer Institute (NCI)–designated Comprehensive Cancer Centers, may have different practice patterns regarding the use of high-cost cancer drugs than nonacademic physicians. Materials and Methods For this cohort study, we linked cancer registry, administrative, and demographic data for patients with newly diagnosed cancer in North Carolina from 2004 to 2011. We selected cancer types with multiple U.S. Food and Drug Administration–approved, National Comprehensive Cancer Network–recommended treatment options and large differences in reimbursement between higher-priced and lower-priced options (stage IV colorectal, stage IV lung, and stage II–IV head-and-neck cancers). We assessed whether provider's practice setting—NCI-designated Comprehensive Cancer Center (“NCI”) versus other location (“non-NCI”)—was associated with use of higher-cost treatment options. We used inverse probability of exposure weighting to control for patient characteristics. Results Of 800 eligible patients, 79.6% were treated in non-NCI settings. Patients treated in non-NCI settings were more likely to receive high-cost treatment than patients treated in NCI settings (36.0% vs. 23.2%), with an unadjusted prevalence difference of 12.7% (95% confidence interval [CI], 5.1%–20.0%). After controlling for potential confounding factors, non-NCI patients remained more likely to receive high-cost treatment, although the strength of association was attenuated (adjusted prevalence difference, 9.6%; 95% CI −0.1%–18.7%). Exploratory analyses suggested potential heterogeneity across cancer type and insurance status. Conclusion Use of higher-cost cancer treatments may be more common in non-NCI than NCI settings. This may reflect differential implementation of clinical evidence, local practice variation, or possibly a response to the reimbursement incentives presented by chemotherapy billing.

Background Multiple claims-based proxy measures of poor function have been developed to address confounding in observational studies of drug effects in older adults. We evaluated agreement between these measures and their associations with treatment receipt and mortality in a cohort of older colon cancer patients. Methods Medicare beneficiaries age 66+ diagnosed with stage II-III colon cancer were identified in the Surveillance, Epidemiology, and End Results-Medicare database (2004-2011). Poor function was operationalized by: (1) summing the total poor function indicators for each model; and (2) estimating predicted probabilities of poor function at diagnosis. Agreement was evaluated using Fleiss' κ and Spearman's correlation. Associations between proxy measures and: (1) laparoscopic versus open surgery; (2) chemotherapy versus none; (3) 5-fluorouracil (5FU)+oxaliplatin (FOLFOX) versus 5FU monotherapy; and (4) 1-year mortality were estimated using log-binomial regression, controlling for age, sex, stage, and comorbidity. Survival estimates were stratified by functional group, age, and comorbidity. Results Among 29,687 eligible colon cancer patients, 67% were 75+ years and 45% had stage III disease. Concordance across the poor function indicator counts was moderate (κ: 0.64) and correlation of predicted probability measures varied (ρ: 0.21-0.74). Worse function was associated with lower chemotherapy and FOLFOX receipt, and higher 1-year mortality. Within age and comorbidity strata, poor function remained associated with mortality. Conclusions While agreement varied across the claims-based proxy measures, each demonstrated anticipated associations with treatment receipt and mortality independent of comorbidity. Claims-based comparative effectiveness studies in older populations should consider applying one of these models to improve confounding control.

Upfront chemoradiation with omission of surgery (CR-only) is increasingly being used to treat rectal cancer. When CR-only is used with curative intent, intense surveillance is recommended. We hypothesized that in practice, few patients treated with CR-only receive intensive post-treatment surveillance.Using Surveillance, Epidemiology, and End Results (SEER)-Medicare, all nonmetastatic rectal cancer patients (≥66 years old) diagnosed from 2004 to 2012, who received upfront chemoradiation, were included. Patients who received CR-only were compared with patients receiving neoadjuvant therapy plus proctectomy. In the 24 months after treatment, markers of surveillance, including carcinoembryonic antigen testing (CEA), endoscopy, and imaging, were compared between groups.A total of 2,482 individuals met the inclusion criteria: 21% (n = 514) had CR-only and 79% had conventional treatment (ie chemoradiation plus proctectomy). Only 2.5% and 3.4% of those in the CR-only and conventional treatment groups, respectively, were in complete compliance with National Comprehensive Cancer Network surveillance guidelines during the first 2 years post-treatment (p0.01). The CR-only group was less likely than the conventional treatment group to receive: CEA (adjusted risk ratio [aRR] 0.57; 95% CI 0.50 to 0.65), endoscopy (aRR 0.76; 95% CI 0.66 to 0.87), and office visits (aRR 0.88; 95% CI 0.84 to 0.92), respectively. However, there were similar rates of cross-sectional imaging between groups (aRR 1.31; 95% CI 0.93 to 1.85).Adherence to guideline-recommended surveillance was poor for all Medicare patients with rectal cancer. Despite recommendations for closer follow-up, patients treated with CR-only were less likely to receive surveillance than those treated with conventional treatment. Efforts should be made to increase adherence to surveillance guidelines for all rectal cancer patients treated with curative intent, but particularly for those with higher risk of recurrence, such as those treated with CR-only.

BACKGROUND Methods developed to estimate intervention effects in external target populations assume that all important effect measure modifiers have been identified and appropriately modeled. Propensity score-based diagnostics can be used to assess the plausibility of these assumptions for weighting methods. METHODS We demonstrate the use of these diagnostics when assessing the transportability of treatment effects from the standard of care for metastatic colorectal cancer control arm in a phase III trial (HORIZON III) to a target population of 1,942 Medicare beneficiaries age 65+ years. RESULTS In an unadjusted comparison, control arm participants had lower mortality compared with target population patients treated with the standard of care therapy (trial vs. target hazard ratio [HR] = 0.72, 95% confidence interval [CI], 0.58, 0.89). Applying inverse odds of sampling weights attenuated the trial versus target HR (weighted HR = 0.96, 95% CI = 0.73, 1.26). However, whether unadjusted or weighted, hazards did not appear proportional. At 6 months of follow-up, mortality was lower in the weighted trial population than the target population (weighted trial vs. target risk difference [RD] = -0.07, 95% CI = -0.13, -0.01), but not at 12 months (weighted RD = 0.00, 95% CI = -0.09, 0.09). CONCLUSION These diagnostics suggest that direct transport of treatment effects from HORIZON III to the Medicare population is not valid. However, the proposed sampling model might allow valid transport of the treatment effects on longer-term mortality from HORIZON III to the Medicare population treated in clinical practice. See video abstract at, http://links.lww.com/EDE/B435.

Background and objectives Older adults with ESRD often receive care in skilled nursing facilities (SNFs) after an acute hospitalization; however, little is known about acute care use after SNF discharge to home. Design, setting, participants, & measurements This study used Medicare claims for North and South Carolina to identify patients with ESRD who were discharged home from a SNF between January 1, 2010 and August 31, 2011. Nursing Home Compare data were used to ascertain SNF characteristics. The primary outcome was time from SNF discharge to first acute care use (hospitalization or emergency department visit) within 30 days. Cox proportional hazards models were used to identify patient and facility characteristics associated with the outcome. Results Among 1223 patients with ESRD discharged home from a SNF after an acute hospitalization, 531 (43%) had at least one rehospitalization or emergency department visit within 30 days. The median time to first acute care use was 37 days. Characteristics associated with a shorter time to acute care use were black race (hazard ratio [HR], 1.25; 95% confidence interval [95% CI], 1.04 to 1.51), dual Medicare-Medicaid coverage (HR, 1.24; 95% CI, 1.03 to 1.50), higher Charlson comorbidity score (HR, 1.07; 95% CI, 1.01 to 1.12), number of hospitalizations during the 90 days before SNF admission (HR, 1.12; 95% CI, 1.03 to 1.22), and index hospital discharge diagnoses of cellulitis, abscess, and/or skin ulcer (HR, 2.59; 95% CI, 1.36 to 4.45). Home health use after SNF discharge was associated with a lower rate of acute care use (HR, 0.72; 95% CI, 0.59 to 0.87). There were no statistically significant associations between SNF characteristics and time to first acute care use. Conclusions Almost one in every two older adults with ESRD discharged home after a post-acute SNF stay used acute care services within 30 days of discharge. Strategies to reduce acute care utilization in these patients are needed.

Background: Older adults are often exposed to multiple medications, some of which could be inappropriate or have the potential to interact with each other. Older cancer patients may be at increased risk for medication-related problems due to exposure to cancer-directed treatment. Methods: We described patterns of potentially inappropriate medication (PIM) use and potential drug–chemotherapy interactions among adults age 66+ years diagnosed with stage I–III breast, stage II–III colon, and stage I to II lung cancer. Within the Surveillance, Epidemiology, and End Results–Medicare database, patients had to have Medicare Part D coverage with 1+ prescription in the diagnosis month and Medicare Parts A/B coverage in the prior 12 months. We estimated monthly prevalence of any and cancer-related PIM from 6 months pre- to 23 months postcancer diagnosis and 12-month period prevalence of potential drug–chemotherapy interactions. Results: Overall, 19,318 breast, 7,283 colon, and 7,237 lung cancer patients were evaluated. Monthly PIM prevalence was stable prediagnosis (37%–40%), but increased in the year following a colon or lung cancer diagnosis, and decreased following a breast cancer diagnosis. Changes in PIM prevalence were driven primarily by cancer-related PIM in patients on chemotherapy. Potential drug–chemotherapy interactions were observed in all cohorts, with prevalent interactions involving hydrochlorothiazide, warfarin, and proton-pump inhibitors. Conclusions: There was a high burden of potential medication-related problems among older cancer patients; future research to evaluate outcomes of these exposures is warranted. Impact: Older adults diagnosed with cancer have unique medication management needs. Thus, pharmacy specialists should be integrated into multidisciplinary teams caring for these patients. Cancer Epidemiol Biomarkers Prev; 27(1); 41–49. ©2017 AACR.

111 Background: Advanced lung cancer (ALC) is a symptomatic disease often diagnosed in the context of hospitalization. The index hospitalization may be a window of opportunity to improve care delivery. We aimed to identify newly diagnosed ALC patients at highest risk for subsequent healthcare utilization. Methods: We identified patients in SEER-Medicare with: ALC (stage IIIB-IV SCLC or NSCLC), diagnosed 2007-13; continuous enrollment -6 months from diagnosis through death or 12/2014; and an index hospitalization within 7 days of ALC diagnosis. Our primary outcomes were 30-day re-hospitalization and emergency department (ED) use. We used a time-to-event model with multivariate regression to identify risk factors. Results: Of ALC patients in SEER-Medicare, 54% (n=28,976) had an index hospitalization. Of those who survived to discharge, by 6 months, 47% had been re-hospitalized, and 50% had enrolled in hospice. Only 37% of patients ever received systemic treatment for their cancer, and the median time to treatment was 46 days. The 30-day ED visit and readmission rates were 13% and 35%, respectively. Pre-cancer ED use or hospitalization, SCLC, and prolonged length of stay were associated with higher risk of 30-day utilization. Palliative care consultation and discharge to hospice were associated with substantially lower risk of 30-day readmission. Conclusions: Many newly diagnosed ALC patients experience an early return to the hospital. These patients may benefit from increased access to palliative and other supportive care during index hospitalization to prevent subsequent healthcare utilization. [Table: see text]

e18386 Background: Advanced lung cancer (ALC) is a symptomatic disease that is often diagnosed in the context of hospitalization. The index hospitalization may be a window of opportunity to improve cancer care delivery. We aimed to define the frequency of ALC diagnosis associated with hospitalization and the relationship to subsequent cancer care and readmissions. Methods: We identified patients in the SEER-Medicare database with: ALC (stage IIIB-IV non-small cell or small cell), diagnosed 2007 to 2013; with continuous enrollment in Medicare from 6 months prior to lung cancer diagnosis through death or 12/2014; and an index hospitalization within 7 days of their ALC diagnosis. Our primary outcomes of interest were 30-day re-hospitalization and emergency department (ED) use. We examined: utilization of services during index hospitalization, including intensive care and oncology or palliative care consultation; discharge destination; receipt of systemic therapy; and hospice enrollment. Results: Fifty-four percent (n = 28,976) of ALC patients had an index hospitalization, with 90% of those having their cancer diagnosed while hospitalized. During their index hospitalization, 16% had oncology consultation, and 6% had palliative care (PC) consultation. Thirty-three percent were in the intensive care unit. At discharge, 59% returned home, 8% died, and 11% went to hospice. Of those who survived to discharge, 69% later returned to the ED or were re-hospitalized, with 49% of re-hospitalizations and 35% of ED visits occurring within 30 days of the index hospitalization. Thirty-five percent of these patients eventually received systemic treatment for their cancer. By 180 days post-discharge, 77% had enrolled in hospice with a median of 10 days on hospice care. Conclusions: Newly diagnosed ALC patients are high risk for acute care utilization, and many patients experience a return to the hospital early in their cancer trajectory. These patients may benefit from additional health system support prior to hospital discharge to help prevent high-cost, low-value healthcare utilization.

Purpose Trastuzumab is a key component of adjuvant therapy for stage I to III human epidermal growth factor receptor 2 (HER2)–positive breast cancer. The rates and patterns of trastuzumab use have never been described in a population-based sample. The recent addition of HER2 information to the SEER-Medicare database offers an opportunity to examine patterns of trastuzumab use and to evaluate possible disparities in receipt of trastuzumab. Methods We examined a national cohort of Medicare beneficiaries with incident stage I to III HER2-positive breast cancer diagnosed in 2010 and 2011 (n = 1,362). We used insurance claims data to track any use of trastuzumab in the 12 months after diagnosis as well as to identify chemotherapy drugs used in partnership with trastuzumab. We used modified Poisson regression analysis to evaluate the independent effect of race on likelihood of receiving trastuzumab by controlling for clinical need, comorbidity, and community-level socioeconomic status. Results Overall, 50% of white women and 40% of black women received some trastuzumab therapy. Among women with stage III disease, 74% of whites and 56% of blacks received trastuzumab. After adjustment for tumor characteristics, poverty, and comorbidity, black women were 25% less likely to receive trastuzumab within 1 year of diagnosis than white women (risk ratio, 0.745; 95% CI, 0.60 to 0.93). Conclusion Approxemately one half of patients 65 years of age and older with stage I to III breast cancer do not receive trastuzumab-based therapy, which includes many with locally advanced disease. Significant racial disparities exist in the receipt of this highly effective therapy. Further research that identifies barriers to use and increases uptake of trastuzumab could potentially improve recurrence and survival outcomes in this population, particularly among minority women.

Aim: Although PET imaging is sometimes used in follow-up of pancreatic cancer, evidence regarding comparative effectiveness of PET and older imaging modalities is limited. Patients & methods: Linked cancer registry and Medicare claims data were analyzed to examine patterns of imaging and effects on treatment patterns and survival among newly diagnosed pancreatic cancer patients from 2003 to 2007. Results: 12% of patients received PET during follow-up. In a time-varying exposure model, computed tomography/MRI was associated with lower mortality risk relative to PET in surgical patients (HR: 0.66; 95% CI: 0.52–0.83). In a subset analysis, type of follow-up imaging before 180 days was not associated with mortality after 180 days (computed tomography/MRI vs PET; hazard ratio: 0.98; 95% CI: 0.84–1.16). Conclusion: Follow-up PET is uncommon among Medicare beneficiaries with pancreatic cancer, and is generally used late in the disease course. This pattern of PET use was not associated with decreased mortality risk compared with conventional imaging.

Objectives To describe the time to first acute care use (e.g., emergency department (ED) use without hospitalization or rehospitalization) for older adults discharged to home after receiving postacute care in skilled nursing facilities (SNFs); to identify predictors of first acute care use. Design Retrospective cohort study using administrative claims data. Setting SNFs providing postacute care for patients in North and South Carolina (N = 1,474). Participants A cohort of Medicare beneficiaries aged 65 and older (N = 55,980) who were hospitalized and then transferred to a SNF for postacute care and subsequently discharged home (January 1, 2010, to August 31, 2011). Measurements Medicare institutional claims data (Parts A and B) and Medicare enrollment data were used; facility-level variables were obtained from CMS Nursing Home Compare. Survival from SNF discharge to first acute care use was explored. Cox proportional hazards regression models were used to describe individual-, home care–, and nursing facility–level predictors. Results After discharge from SNF to home, 22.1% of older adults had an episode of acute care use within 30 days, including 7.2% with an ED visit without hospitalization and 14.8% with a rehospitalization; 37.5% of older adults had their first acute care use within 90 days. Male sex, dual eligibility status, higher Charlson comorbidity score, certain primary diagnoses at index hospitalization (neoplasms and respiratory disease), and care in SNFs with for-profit ownership or fewer licensed practical nurses hours per patient-day were associated with greater likelihood of acute care use. Conclusion Medicare beneficiaries have a high use of acute care services after discharge from SNFs, and several factors associated with acute care use are potentially modifiable. Findings suggest the need for interventions to support beneficiaries as they transition from SNFs to home.

10052Background: The incidence of specific complications of adjuvant chemotherapy in breast cancer is well documented in clinical trials. However, the effect of chemotherapy on functional outcomes ...

6129 Background: Patients with an elevated prostate specific antigen (PSA) level need to travel to a urologist for diagnostic biopsy; once diagnosed, travel to a urologist or radiation oncologist f...