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Julie Beyrer,1,&ast; David R Nelson,1,&ast; Kristin M Sheffield,1,&ast; Yu-Jing Huang,1,&ast; Yiu-Keung Lau,1,&ast; Ana L Hincapie2,&ast; 1Eli Lilly and Company, Indianapolis, IN, USA; 2University of Cincinnati James L. Winkle College of Pharmacy, Cincinnati, OH, USA&ast;These authors contributed equally to this workCorrespondence: Julie Beyrer, Eli Lilly and Company, Lilly Corporate Center, Indianapolis, IN, 46285, USA, Tel +1 317 651 8236, Email beyrerj@lilly.comPurpose: We sought to develop and validate an incident non-small cell lung cancer (NSCLC) algorithm for United States (US) healthcare claims data. Diagnoses and procedures, but not medications, were incorporated to support longer-term relevance and reliability.Methods: Patients with newly diagnosed NSCLC per Surveillance, Epidemiology, and End Results (SEER) served as cases. Controls included newly diagnosed small-cell lung cancer and other lung cancers, and two 5% random samples for other cancer and without cancer. Algorithms derived from logistic regression and machine learning methods used the entire sample (Approach A) or started with a previous algorithm for those with lung cancer (Approach B). Sensitivity, specificity, positive predictive values (PPV), negative predictive values, and F-scores (compared for 1000 bootstrap samples) were calculated. Misclassification was evaluated by calculating the odds of selection by the algorithm among true positives and true negatives.Results: The best performing algorithm utilized neural networks (Approach B). A 10-variable point-score algorithm was derived from logistic regression (Approach B); sensitivity was 77.69% and PPV = 67.61% (F-score = 72.30%). This algorithm was less sensitive for patients ≥ 80 years old, with Medicare follow-up time < 3 months, or missing SEER data on stage, laterality, or site and less specific for patients with SEER primary site of main bronchus, SEER summary stage 2000 regional by direct extension only, or pre-index chronic pulmonary disease.Conclusion: Our study developed and validated a practical, 10-variable, point-based algorithm for identifying incident NSCLC cases in a US claims database based on a previously validated incident lung cancer algorithm.Keywords: algorithm, machine learning, medicare claims, non-small cell lung cancer, positive predictive value, sensitivity, validation

This retrospective, observational study examined patient characteristics, treatment patterns, testing patterns, and outcomes of US patients receiving first-/second- or third-generation epidermal gr...

This retrospective observational study described baseline characteristics, real-world treatment patterns, and outcomes among patients with metastatic breast cancer treated with abemaciclib in the United States.De-identified electronic health record-derived data were used to describe patients who began abemaciclib treatment on or after 30 June 2016 and ≥4 months before data cutoff (31 December 2018). Real-world response (rwR) and real-world progression assessments were abstracted from clinical documentation. Descriptive statistics were used to calculate the real-world best response. The Kaplan-Meier method estimated real-world time to first response (rwTTFR) and real-world progression-free survival (rwPFS).The median age of 118 female patients at abemaciclib initiation was 66.5 years (interquartile range, 57.0, 73.0). The breakdown of patients who received abemaciclib in first, second, third, or later lines was 28.8%, 21.2%, 20.3%, and 29.7%, respectively. Patients received abemaciclib as monotherapy (12.7%) or in combination with endocrine therapy: fulvestrant (59.3%); aromatase inhibitor (22.9%); aromatase inhibitor and fulvestrant (5.1%). There were 68 patients (57.6%) with ≥1 rwR assessment: 41.2% with a real-world complete response or real-world partial response. Median rwTTFR was 3.6 months (95% confidence interval, 3.5, 5.2). Twelve-month rwPFS probability was 61.7%.This study represents utilization and outcomes associated with abemaciclib approximately 1 year following FDA approval. Treatment patterns demonstrated heterogeneity and, as in clinical trials, patients appeared to benefit from abemaciclib treatment in the real world. More research investigating outcomes associated with abemaciclib treatment is needed, with larger samples and longer follow-up to enable closer evaluation by subgroup, regimen, and line of therapy.

Aim: To assess invasive disease-free survival (IDFS) and distant relapse-free survival (DRFS) in hormone receptor-positive, HER2-negative early breast cancer with combined clinicopathological criteria from monarchE, a phase III study of abemaciclib. Methods: US electronic health records were used to compare outcomes between high-risk (≥4 lymph nodes, or 1–3 lymph nodes and grade 3, tumor ≥5 cm or Ki-67 ≥20%) versus nonhigh-risk groups using Kaplan–Meier methods and Cox regression models. Results: The high-risk group (n = 557) was at higher risk for IDFS and DRFS events than the nonhigh-risk group (n = 3471). IDFS events (hazard ratio: 3.07; 95% CI: 2.45–3.83) and DRFS events (hazard ratio: 3.15; 95% CI: 2.49–3.97) were significantly higher for the high-risk group. Conclusion: Risk of recurrence was three-times greater in the high-risk group, highlighting the need for better therapies.

Purpose In MONARCH 1 (NCT02102490), single-agent abemaciclib demonstrated promising efficacy activity and tolerability in a population of heavily pretreated women with refractory HR+, HER2− metastatic breast cancer (MBC). To help interpret these results and put in clinical context, we compared overall survival (OS) and duration of therapy (DoT) between MONARCH 1 and a real-world single-agent chemotherapy cohort. Methods The real-world chemotherapy cohort was created from a Flatiron Health electronic health records-derived database based on key eligibility criteria from MONARCH 1. The chemotherapies included in the cohort were single-agent capecitabine, gemcitabine, eribulin, or vinorelbine. Results were adjusted for baseline demographics and clinical differences using Mahalanobis distance matching (primary analysis) and entropy balancing (sensitivity analysis). OS and DoT were analyzed using the Kaplan–Meier method and Cox proportional hazards regression. Results A real-world single-agent chemotherapy cohort (n = 281) with eligibility criteria similar to the MONARCH 1 population (n = 132) was identified. The MONARCH 1 (n = 108) cohort was matched to the real-world chemotherapy cohort (n = 108). Median OS was 22.3 months in the abemaciclib arm versus 13.6 months in the matched real-world chemotherapy cohort with an estimated hazard ratio (HR) of 0.54. The median DoT was 4.1 months in MONARCH 1 compared to 2.9 months in the real-world chemotherapy cohort with HR of 0.76. Conclusions This study demonstrates an approach to create a real-world chemotherapy cohort suitable to serve as a comparator for trial data. These exploratory results suggest a survival advantage and place the benefit of abemaciclib monotherapy in clinical context.

BACKGROUND Primary tumor location is a prognostic factor for metastatic colorectal cancer (mCRC). Post hoc analyses of mCRC clinical trials, including FIRE-3, CALGB/SWOG 80405, suggest that primary tumor location is also predictive of survival benefit with cetuximab or bevacizumab in combination with 5-fluorouracil-based chemotherapy. AIM Evaluate prognostic/predictive roles of primary tumor location in real-world mCRC patients treated with cetuximab or bevacizumab plus 5-fluorouracil-based chemotherapy. METHODS This retrospective cohort study selected patients with KRAS wild-type mCRC who initiated first-line therapy with cetuximab or bevacizumab in combination with 5-fluorouracil/leucovorin/irinotecan (FOLFIRI) or 5-fluorouracil/ leucovorin/oxaliplatin (FOLFOX) between January 2013 and April 2017 from the Flatiron Health electronic health record-derived database of de-identified patient-level data in the United States. Primary tumor location was abstracted from patients’ charts. Left-sided primary tumor location (LPTL) was defined as tumors that originated in the splenic flexure, descending colon, sigmoid colon, or rectum; right-sided primary tumor location (RPTL) was defined as tumors that originated from the appendix, cecum, ascending colon, hepatic flexure, or transverse colon. Propensity score matching was used to balance the baseline demographic and clinical characteristics between patients treated with cetuximab and patients treated with bevacizumab. Kaplan-Meier and Cox regression methods were used for survival analyses. RESULTS A total of 1312 patients met the selection criteria. Of 248 cetuximab plus FOLFIRI or FOLFOX patients, 164 had LPTL and 84 had RPTL; of 1064 bevacizumab plus FOLFIRI or FOLFOX patients, 679 had LPTL and 385 had RPTL. Cetuximab LPTL and RPTL patients were more likely to receive FOLFIRI vs bevacizumab patients (LPTL: 64.0% vs 24.3%; RPTL: 76.2% vs 24.9%, P < 0.001). Stage at initial diagnosis was different between cetuximab RPTL vs bevacizumab RPTL patients (P < 0.001); cetuximab RPTL patients were more likely to have stage III disease (44.0% vs 22.6%), while bevacizumab RPTL patients were more likely to have stage IV disease (65.7% vs 48.8%). Cetuximab RPTL patients were more likely to have a documented history of adjuvant chemotherapy vs bevacizumab RPTL patients (47.6% vs 22.3%, P < 0.001). In the propensity score-matched sample, median overall survival (OS) was 29.7 mo (95%CI: 26.9-35.2) for LPTL patients vs 18.3 mo (95%CI: 15.8-21.3) for RPTL patients (P < 0.001). Median OS was 29.7 mo (95%CI: 27.4-NA) for cetuximab LPTL patients vs 29.1 mo (95%CI: 26.6-35.6) for bevacizumab LPTL patients (HR = 0.87; 95%CI: 0.63-1.19; P = 0.378) and 17.0 mo (95%CI: 12.0-32.6) for cetuximab RPTL patients vs 18.8 mo (95%CI: 15.8-22.3) for bevacizumab RPTL patients (HR = 1.00; 95%CI: 0.68-1.46; P = 0.996). The interaction of treatment and primary tumor location was not significant in the Cox regression. CONCLUSION In this real-world mCRC cohort, the prognostic role of primary tumor location was substantiated, but not the predictive role for treatment with cetuximab vs bevacizumab in combination with 5-fluorouracil-based chemotherapy.

Background: Abemaciclib is a selective continually dosed cyclin-dependent kinase 4 and 6 (CDK 4&6) inhibitor approved as a single agent and in combination with endocrine therapy for the treatment of HR+,HER2- metastatic breast cancer (MBC). To date, few publications have reported the real world (rw) use of abemaciclib. This retrospective observational study aimed to describe baseline characteristics, treatment patterns, and outcomes among MBC patients treated with abemaciclib in the US. Methods: HR+,HER2- MBC patients who initiated treatment with abemaciclib on or after 6/30/2016 and at least 4 months prior to the data cutoff date (12/31/2018) were selected from the de-identified Flatiron Health electronic-health record-derived database for US patients. The data were predominantly from a community oncology setting. Baseline demographic and clinical characteristics were recorded at the start of abemaciclib therapy. Using technology-enabled abstraction, rw tumor response (rwTR) assessments on abemaciclib were collected to calculate rw best response (rwBR) which was defined as rw complete (rwCR) or partial response (rwPR). Time to first response (rwTTFR) was estimated using the Kaplan-Meier method. Descriptive statistics were used to summarize baseline characteristics and treatment patterns. Results: 118 female MBC patients were treated with abemaciclib. Baseline characteristics are shown in Table 1. Median age at abemaciclib initiation was 66.5 years (interquartile range [IQR] 57-73). 28.8% of patients received abemaciclib in first line (1L), 21.2% in second line (2L), 20.3% in third line (3L), and 29.7% in later lines (4+L). 12.7% of patients (n=15) received abemaciclib as a monotherapy, occurring mostly in later lines. Patients also received abemaciclib in combination with endocrine therapy, including fulvestrant (59.3%), or aromatase inhibitor (22.9%), or other treatment (5.1%). 24.6% of patients received prior treatment with a different CDK 4&6 inhibitor. Most patients (81.3%) had a starting dose of 150 mg of abemaciclib, while other starting doses included 200 mg (8.4%), 100 mg (4.2%), 50 mg (3.4%), or unknown dose (2.5%). During treatment, 6.8%, and 21.2% of patients had a dose reduction or schedule change, respectively. Of the patients with a schedule change (n=25), 72% changed from twice to once daily. Among all abemaciclib patients who had at least 1 rwTR assessment (n=68), 41.2% had a rwBR. Although not statistically significant, there was a trend toward higher rates of rwBR in 1L (65.0%) compared to 2L (37.4%), 3L (35.7%), and 4+L (22.3%). Median rwTTFR was 3.6 months (95% CI: 3.5-5.2). Conclusions: This is one of the first studies describing rw utilization of abemaciclib, and it provides initial insights into scheduling and dosing in an rw population. There is evidence of response to abemaciclib even in later lines. Future research will be needed as treatment patterns evolve and longer follow-up periods are available to further describe patient outcomes. Table 1: Baseline patient characteristicsAbemaciclibN = 118%Race:White63.6Non-white20.3Unknown/missing16.1Stage at initial diagnosis:I11.9II16.1III28.8IV34.7Not documented8.5Tumor grade at initial diagnosis:Grade 19.3Grade 245.8Grade 322.9Unknown/not documented22.0Time between initial and metastatic diagnosis dates among patients who were not metastatic at initial diagnosisa:< 2 years20.8≥ 2 years79.2Menopausal statusb:Post-menopausal93.2Pre-menopausal6.8Modified Charlson comorbidity index (CCI) statusc:0/Unknown72.0116.928.53+2.5Number of sites of metastases, median [IQR]d2.0 [1.0:3.0]Presence of lung metastases34.7Presence of liver metastases22.9Presence of brain metastases7.6Follow-up time (months), median [IQR]6.4 [4.1:9.5]a: Patients not metastatic at initial diagnosis (n=77)b: Derived using age and evidence of gonadotropin-releasing hormone agonistc: Excludes cancer diagnosisd: Interquartile Range (IQR) Citation Format: Gebra Cuyun Carter, Kristin M Sheffield, Anala Gossai, Yu-Jing Huang, Yajun Emily Zhu, Lee Bowman, Emily Nash Smith, Raina Mathur, Aaron B Cohen, Shrujal Baxi, Sarah Rybowski, Amy Lee Chong, Andrew D Seidman. Initial real world treatment patterns and outcomes of Abemaciclib for the treatment of HR+,HER2- metastatic breast cancer [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 P2-08-12.

Bone pain is one of the most common forms of pain reported by cancer patients with metastatic disease. We conducted a review of oncology literature to further understand the epidemiology of and treatment approaches for metastatic cancer-induced bone pain and the effect of treatment of painful bone metastases on the patient's quality of life. Two-thirds of patients with advanced, metastatic, or terminal cancer worldwide experience pain. Cancer pain due to bone metastases is the most common form of pain in patients with advanced disease and has been shown to significantly reduce patients' quality of life. Treatment options for cancer pain due to bone metastases include nonsteroidal anti-inflammatory drugs, palliative radiation, bisphosphonates, denosumab, and opioids. Therapies including palliative radiation and opioids have strong evidence supporting their efficacy treating cancer pain due to bone metastases; other therapies, like bisphosphonates and denosumab, do not. There is sufficient evidence that patients who experience pain relief after radiation therapy have improved quality of life; however, a substantial proportion are nonresponders. For those still requiring pain management, even with available analgesics, many patients are undertreated for cancer pain due to bone metastases, indicating an unmet need. The studies in this review were not designed to determine why cancer pain due to bone metastases was undertreated. Studies specifically addressing cancer pain due to bone metastases, rather than general cancer pain, are limited. Additional research is needed to determine patient preferences and physician attitudes regarding choice of analgesic for moderate to severe cancer pain due to bone metastases.

Background: Previous studies have highlighted concerns regarding treatment persistence (TP) of patients with early breast cancer (EBC) taking adjuvant endocrine therapy (ET) but these data have not been analyzed based on patient’s risk of recurrence. The aim of this study is to evaluate the TP of patients at high risk of recurrence based on clinicopathologic criteria used in the monarchE trial. Methods: This observational retrospective cohort study used nationwide Flatiron Health electronic health record (EHR)-derived de-identified database of US patients diagnosed with EBC from Jan 2011 to Sept 2020. Overall, 4028 patients were selected based on the following criteria: adult female or male with diagnosis of HR+, HER2– EBC (stage IA-IIIC) with no evidence of distant metastasis who received surgical resection and adjuvant endocrine therapy. Patients were divided into 2 groups; GroupA: patients with clinicopathologic features suggestive of high risk of recurrence: ≥4 positive(+) axillary lymph nodes (ALN), OR 1-3+ ALN and either Grade3 disease, or tumor size ≥ 5 cm, or Ki-67 ≥ 20%. GroupB: patients with stage IA-IIIC disease who did not meet those high risk criteria. TP (time from start to discontinuation of adjuvant ET) was compared between the 2 groups. Patients who had a gap of >90 days after their last date of ET, as documented in the EHR, were considered to have discontinued ET. Patients whose last ET was ≤90 days from Sept 2020 were censored. Cumulative incidence functions of nonpersistence were estimated, treating recurrences or deaths occurring during ET as competing risks. Results: While gender and race distributions were similar between groups, patients in GroupA (n=557) were younger and more likely to be premenopausal, have an ECOG PS score of 1 or 2+, and have received mastectomy, radiation and chemotherapy compared to GroupB (n=3471). Estimates of the cumulative incidence functions of nonpersistence were statistically different between the groups (p Conclusions: This study suggests that patients at high risk of recurrence have higher ET-TP than those at lower risk. The separation was most pronounced at 5 years. The steep increase in 5-year nonpersistence in lower risk group could be due to a perception of less need to continue ET for longer periods of time in lower risk disease. The greater persistence in patients at high risk is noteworthy, but interventions to improve patient’s TP are still warranted. Table 1: Cumulative incidence of nonpersistence after initiating ET Citation Format: Kristin M. Sheffield, Alexandra S. Vitko, Jacqueline Brown. Persistence with adjuvant endocrine therapy in patients with early breast cancer at high risk of recurrence: a US-based real-world study [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr P4-03-01.

To examine the real-world incidence and management of select adverse events (AEs) among female patients with hormone receptor positive (HR+), human epidermal growth factor receptor 2-negative (HER2−) metastatic breast cancer (MBC), receiving a cyclin-dependent kinase 4 and 6 (CDK4 and 6) inhibitor (palbociclib, abemaciclib, or ribociclib). This retrospective study analyzed data from the US Oncology Network iKnowMed electronic health record database for 396 patients with an initial MBC diagnosis on/after 1 January 2014 and receipt of first CDK4 and 6 regimen between 1 January 2017 and 31 December 2018. In this descriptive study, the proportion of patients who experienced select AEs and associated dose modifications or discontinuations were reported. The occurrence of select healthcare resource utilization categories was also reported. Median follow-up time was 451, 262, and 355 days for patients in the palbociclib, abemaciclib, and ribociclib cohorts, respectively. The most common AEs were neutropenia (palbociclib, 44.8%; abemaciclib, 10.6%; ribociclib, 36.3%), diarrhea (palbociclib, 8.0%; abemaciclib, 43.0%; ribociclib, 8.8%), and fatigue (palbociclib, 12.9%; abemaciclib, 17.6%; ribociclib, 16.5%). AEs resulted in a treatment hold among 91 (23.0%), a dose reduction among 86 (21.7%), and permanent discontinuation among 48 (12.1%) patients overall. This real-world study provides insight into the occurrence of AEs which varied by CDK4 and 6 inhibitor. Compared to clinical trials, frequencies of AEs were numerically lower but dose reductions due to AEs were numerically higher. It is possible these differences reflect proactive management of AEs on the part of clinicians to help patients remain on therapy. Cyclin-dependent kinase 4 and 6 inhibitors (CDK4 and 6 inhibitors) have changed the landscape for the treatment of metastatic breast cancer (MBC) among patients who are hormone receptor positive (HR+) and human epidermal growth factor receptor 2 negative (HER2−). An understanding of the real-world management of adverse events (AEs) will help optimize treatment strategies. Here, data from the US Oncology Network electronic health record database for 396 HR+, HER2−, MBC patients receiving a CDK4 and 6 inhibitor were examined to describe the proportion of patients who experienced select AEs and the associated outcomes of these AEs. Compared to clinical trials, frequencies of AEs were numerically lower but dose reductions due to AEs were numerically higher. It is possible that these differences reflect a proactive management of AEs on the part of clinicians to help patients remain on therapy.

This retrospective, observational study examined patient characteristics, treatment patterns, testing patterns, and outcomes of US patients receiving first-/second- or third-generation epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs).This study used an electronic health record-derived de-identified database. Eligible patients had advancedOf the 782 patients who received first-line (1L) therapy with first-/second-generation EGFR TKIs in cohort A, erlotinib was the most common (58%), and osimertinib was the most widely prescribed second-line (2L) therapy (52%). Of the patients who received 1L therapy with osimertinib, a greater range of treatments were prescribed in 2L. A third of patients treated with first-/second-generation EGFR TKIs underwentThe majority of patients treated with first-/second-generation EGFR TKIs went on to receive osimertinib in the 2L setting, but overall, only a third of patients had received molecular testing at progression. Improved testing frequency is vital to inform treatment decisions.

Background: PTL is a prognostic factor for mCRC. Recent data suggest PTL is also predictive of survival benefit with cetuximab (CET) and bevacizumab (BEV). This study evaluated the prognostic and predictive effect of PTL in patients with KRAS WT mCRC who initiated first-line (1L) therapy with CET vs BEV in the real world. Methods: This retrospective study selected patients with KRAS WT mCRC who initiated 1L therapy with CET or BEV + FOLFIRI or FOLFOX between January 2013 and April 2017 from Flatiron Health’s electronic health record-derived database. PTL was abstracted from patients’ charts. Left-sided PTL (LPTL): splenic flexure to rectum; right-sided PTL (RPTL): cecum to splenic flexure. Propensity score matching was used to balance treatment cohorts on baseline characteristics. Kaplan Meier and Cox regression methods were used for survival analyses. Results: 1,312 patients met the selection criteria. Of 248 CET + FOLFIRI or FOLFOX patients, 164 had LPTL and 84 had RPTL; of 1,064 BEV + FOLFIRI or FOLFOX patients, 679 had LPTL and 385 had RPTL. CET LPTL and RPTL patients were more likely to receive FOLFIRI vs BEV patients (LPTL: 64.0% vs 24.3%; PPPPPP=.378), and 17.0 months (95% CI, 12.0–32.6) for CET RPTL vs 18.8 months (95% CI, 15.8–22.3) for BEV RPTL patients (HR, 1.00; 95% CI, 0.68–1.46; P=.996). The interaction of treatment and PTL was not significant in the Cox regression. Conclusions: This study found a prognostic effect of PTL but not a predictive effect. LPTL patients had significantly longer OS vs RPTL patients. However, the treatment effect for CET vs BEV by PTL was not significantly different. Future research is needed to examine differences between real-world and clinical trial populations that may have contributed to divergent results.

Background In MONARCH 1 (NCT02102490), abemaciclib demonstrated promising single-agent activity and tolerability in a population of heavily pretreated women with refractory HR+, HER2- metastatic breast cancer (MBC).1 Confirmed objective response rate (ORR) was 19.7% (95% CI: 13.3, 27.5) and at 18 months minimum follow-up median overall survival (OS) was 22.3 months. Due to the single-arm trial design of MONARCH 1, there is a need to view these results in clinical context relative to available treatment options. This study compared the OS results of abemaciclib in MONARCH 1 vs that in a real-world single-agent chemotherapy cohort with similar patient and disease characteristics. Methods MONARCH 1 study design and key eligibility criteria were previously described.1 The real-world cohort was based on Flatiron Health electronic health records-derived, nationally representative (USA-based) database comprising patient-level structured and unstructured data, curated via technology-enabled abstraction, for patients with MBC between January 1, 2011 through February 28, 2018. A real-world single-agent chemotherapy cohort was created based on the key eligibility criteria of MONARCH 1 and included patients diagnosed with HR+, HER2- MBC who received single-agent chemotherapy (eribulin, capecitabine, gemcitabine, or vinorelbine) following 1-2 prior chemotherapy regimens in the metastatic setting, had an ECOG PS of 0-1, and no prior CDK4 & 6 therapy. The index date was the start of the eligible single-agent chemotherapy, and patients were followed from the index date until date of death, loss to follow-up, or end of the database, whichever occurred earlier. OS results were adjusted using 2 methods (Mahalanobis distance matching and entropy balancing with bootstrapping) to account for baseline demographic and clinical differences between the real-world and trial cohorts. Results A real-world cohort (n=281) with eligibility criteria similar to the MONARCH 1 population (n=132) was identified. A subsequent matching based on Mahalanobis distance was performed to match MONARCH 1 population (n=108) with the real-world cohort (n=108). The matched cohorts demonstrated similar patient and disease characteristics. Median OS was 22.3 months in the abemaciclib arm vs 13.6 months in the matched cohort with an estimated hazard ratio (HR) of 0.54 (95% CI: 0.37, 0.77). Results of a sensitivity analysis performed using entropy balancing were consistent with an adjusted median OS of 12.7 months in the real-world cohort (n=281)with HR of 0.57 (95% CI from bootstrapping: 0.44, 0.78). Conclusion Methodological advances to adjust for potential biases, and improvements in data quality, have evolved enabling the ability to leverage a real-world cohort as an external comparator arm. This study demonstrates the ability to create a real-world chemotherapy cohort suitable to serve as a comparator for MONARCH 1. These exploratory results suggest a survival advantage and adequately place the clinical benefit of abemaciclib monotherapy in clinical context. References Dickler et al, CCR 2017 Citation Format: Rugo H, Dieras V, Cortes J, Patt D, Wildiers H, O'Shaughnessy J, Zamora E, Yardley DY, Carter GC, Sheffield KM, Li L, Andre VA, Derbyshire RE, Li XI, Frenzel M, Huang Y-J, Dickler MN, Tolaney SM. Real-world survival of heavily pretreated patients with refractory HR+, HER2- metastatic breast cancer receiving single-agent chemotherapy - A comparison with MONARCH 1 [abstract]. In: Proceedings of the 2018 San Antonio Breast Cancer Symposium; 2018 Dec 4-8; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2019;79(4 Suppl):Abstract nr P6-18-19.

Background: Evidence suggests that there are clinical features associated with a less favorable prognosis among patients with HR+/HER2- metastatic breast cancer (MBC) such as metastases to non-bone sites, including liver and lung, and negative progesterone receptor (PgR-) status. The objective of this study was to compare baseline characteristics and outcomes between those with and without these clinical factors among a cohort of HR+/HER2- MBC patients treated with a CDK4&6 inhibitor (CDK4&6i). Methods: This was a retrospective analysis of the Flatiron Health electronic health records-derived database for US patients diagnosed with MBC between 1/1/2011 and 9/30/2017. The study included a random sample of patients with HR+/HER2- MBC who were treated with a CDK4&6i on or after 6/30/2016. Baseline variables, including demographics, comorbidities, and sites of metastasis, were recorded at start of the first CDK4&6i containing line of therapy in the metastatic setting on or after this date. Dates of real-world progression were abstracted from patient charts. Descriptive statistics and appropriate statistical tests were used to compare baseline characteristics between patients with or without select clinical factors associated with unfavorable outcomes. In patients who received a CDK4&6i-based therapy, Kaplan–Meier methods and univariable Cox proportional hazards models were used to assess real-world progression free survival (rwPFS) by line from start of line to the date of first progression or death within line (unadjusted for treatment and other potential confounders). Results: 518 patients were included in this study. Median age at metastatic diagnosis was 66y (IQR; 59-73y); 99% female and 11.4% had PgR- status. At baseline, 20.5%, 46.3%% and 65.8% of patients had liver, visceral (defined as liver and/or lung), and non-bone only metastases, respectively. Among a total of 207 patients who received a CDK4&6i as initial therapy in the metastatic setting, 69.1% received it in combination with an aromatase inhibitor, 29.5% received it in combination with fulvestrant, and 1.4% as monotherapy. Within the same group, 58 had disease progression or died during first line (1L); median rwPFS measured from start of 1L was not reached (95% CI: 10.7 months, NA). Univariable analyses revealed the presence of liver metastases was associated with a higher risk of progression or death compared to no liver metastases (HR: 2.04, 95% CI: 1.13 - 3.68). Having non bone-only metastases was associated with a higher risk of progression or death compared to having bone-only metastases (HR: 2.23, 95% CI: 1.20 – 4.15). Univariable analyses did not reveal any statistically significant differences in first-line rwPFS by PgR status or presence of visceral metastases. Results from other lines of therapy are forthcoming. Conclusion: In a real world data set, and consistent with prior prospective data, presence of liver and non-bone only metastases were associated with a higher risk of progression among patients with HR+/HER2- MBC receiving initial therapy with a CDK4&6i. The heterogeneity of prognoses among this population reinforces the need to consider these clinical features in treatment decisions for optimal patient outcomes. Citation Format: Saverno KR, Carter GC, Li L, Battiato LA, Huang Y-J, Smyth EN, Price GL, Sheffield KM, Baxi SS, Kuk D, Seidman AD. Influence of prognostic factors on outcomes among metastatic breast cancer patients treated with CDK4&6 inhibitors in routine clinical practice [abstract]. In: Proceedings of the 2018 San Antonio Breast Cancer Symposium; 2018 Dec 4-8; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2019;79(4 Suppl):Abstract nr P2-08-38.

Aim: To predict optimal treatments maximizing overall survival (OS) and time to treatment discontinuation (TTD) for patients with metastatic breast cancer (MBC) using machine learning methods on electronic health records. Patients/methods: Adult females with HR+/HER2- MBC on first- or second-line systemic therapy were eligible. Random survival forest (RSF) models were used to predict optimal regimen classes for individual patients and each line of therapy based on baseline characteristics. Results: RSF models suggested greater use of CDK4 & 6 inhibitor-based therapies may maximize OS and TTD. RSF-predicted optimal treatments demonstrated longer OS and TTD compared with nonoptimal treatments across line of therapy (hazard ratios = 0.44∼0.79). Conclusion: RSF may help inform optimal treatment choices and improve outcomes for patients with HR+/HER2- MBC.

The FDA is preparing guidance about using real-world evidence (RWE) to support decisions about product effectiveness. Several ongoing efforts aim to replicate randomized clinical trial (RCT) results using RWE with the intent of identifying circumstances and methods that provide valid evidence of drug effects. Lack of agreement may not be due to faulty methods but rather to the challenges with emulating RCTs, differences in healthcare settings and patient populations, differences in effect measures and data analysis, bias, and/or the efficacy–effectiveness gap. In fact, for some decisions, RWE may lead to better understanding of how treatments work in usual care settings than a more constrained view from RCTs. Efforts to reconcile the role and opportunities for generating complementary evidence from RWE and RCTs will advance regulatory science.

Our aim was to develop and validate a practical US healthcare claims algorithm for identifying incident lung cancer that improves on positive predictive value (PPV) and sensitivity observed in past studies.Patients newly diagnosed with lung cancer in Surveillance, Epidemiology, and End Results (SEER) (gold standard) were linked with Medicare claims. A 5% Medicare "other cancer" sample and noncancer sample served as controls. A split-sample validation approach was used. Rules-based, regression, and machine learning models for developing algorithms were explored. Algorithms were developed in the model building subset. Rules-based algorithms and those with the highest F scores were evaluated in the validation subset. F scores were compared for 1000 bootstrap samples. Misclassification was evaluated by calculating the odds of selection by the algorithm among true positives and true negatives.A practical single-score algorithm derived from a logistic regression model had sensitivity = 78.22% and PPV = 78.50% (F score: 78.36). The algorithm was most likely to misclassify older patients (ages ≥80 years) or with missing data in the SEER registry, shorter follow-up time in Medicare (3 months), insurance through Veterans Affairs,1 cancer in SEER, or certain Charlson comorbidities (dementia, chronic pulmonary disease, liver disease, or myocardial infarction).In this dataset, a practical point-based algorithm for identifying incident lung cancer demonstrated significant and substantial improvement (7.9% and 23.9% absolute improvement in sensitivity and PPV, respectively) compared with a current standard.

Purpose Results of a study in which population-based body weight and body surface area (BSA) data were used for vial size optimization to reduce drug waste associated with administration of the i.v. anticancer agent olaratumab are reported. Methods A retrospective observational study was conducted to determine weight and BSA distributions in a large sample of U.S. oncology patients using data from a large electronic medical record database. Body weight and BSA values at the time of initial systemic anticancer therapy were used to compute olaratumab dose requirements in a cohort of patients with soft tissue sarcoma; those data were analyzed to derive estimates of drug waste likely to result from the use of various proposed olaratumab vial sizes in combination with an existing 500-mg size. Weight and BSA distributions were calculated for additional cohorts of patients with 7 other cancer types. Results Median weight values in men ( n = 1,179) and women ( n = 1,078) with soft tissue sarcoma were 82.55 kg (interquartile range [IQR], 72.58–95.53 kg) and 68.69 kg (IQR, 58.51–84.28 kg), respectively. Modeling of olaratumab dosing scenarios indicated that use of the 500-mg vial only would result in estimated average drug waste of 234 mg per patient per administration; analysis of various potential vial size combinations showed that waste could be reduced by 87.6% with the addition of a 190-mg vial size. Conclusion Analysis of real-world patient weight and BSA data allowed olaratumab vial size optimization to enable maximal dosing flexibility with minimal drug waste.

e18581 Background: While most patients (pts) with HR+, HER2- early breast cancer (EBC) do not experience disease recurrence, those with high risk clinicopathologic features may have recurrence within the first few years on adjuvant endocrine therapy (AET). This study estimates risk of recurrence in pts with EBC based on clinicopathologic features and evaluates the medical need for more efficacious treatments using US oncology practice data. Methods: This retrospective study used the nationwide Flatiron Health electronic health record derived deidentified database. The cohort included pts with HR+, HER2- stage I-III breast cancer, diagnosed Jan 2011-Mar 2020, who received surgery and AET. Clinicopathologic features were used to identify a ‘high risk (HiR) group’ (≥ 4 positive axillary lymph nodes (LN), or 1-3 positive axillary LN and ≥ 1 of the following: Grade 3, tumor size ≥ 5 cm, or Ki-67 ≥ 20%) and ‘low risk (LoR) group’ (pts who do not meet above criteria, including a subset with node negative (N0) disease). Cox proportional hazards regression models compared invasive disease-free survival (IDFS) and distant relapse-free survival (DRFS) from AET initiation between groups according to a sequential gatekeeping strategy and stepwise analysis: first compare HiR group to N0 pts; if significant then compare HiR to LoR group. Results: 557 (13.8%) pts were in the HiR group and 3,471 (86.2%) in the LoR group (including 2,867 N0 pts). The study population (median age 64 yrs) was predominantly female (99.2%), white (69.4%) and postmenopausal (75.6%) with median follow-up of 39.6 months. Pts in the HiR group were younger and more likely premenopausal, have a BRCA mutation, invasive lobular carcinoma and less likely to have received an Oncotype DX test compared to LoR pts. Of the 557 HiR pts, 231 (41.5%) had ≥ 4 positive LN and 326 (58.5%) had 1-3 positive axillary LN with additional risk factor(s): tumor size ≥ 5 cm (11.7%), histologic grade 3 (32.0%), and/or Ki-67 ≥ 20% (31.6%). Most HiR pts received radiotherapy (82.4%) and chemotherapy (68.1%). Significant differences in IDFS and DRFS were observed between HiR group and N0 and LoR groups (logrank test p < .0001 for all). The 2-year IDFS rate was 88.1% in the HiR group, compared to 97.4% in N0 pts and 97.1% in the LoR group; 2-year DRFS rates were 89.0% compared to 97.9% and 97.7%, respectively. Pts in the HiR group had significantly higher hazard of invasive disease recurrence or death compared to N0 (HR = 3.42, 95% CI: 2.69-4.34, p < .0001) and LoR group (HR = 3.07, 95% CI: 2.46-3.84, p < .0001). Similar results observed for DRFS (HiR vs N0: HR = 3.46, 95% CI: 2.70-4.44, p < .0001; HiR vs LoR HR = 3.16, 95% CI: 2.50-3.98, p < .0001). Conclusions: Approximately 12% of pts with EBC and high risk clinicopathologic features experienced invasive disease recurrence or death within 2 years of initiating AET. Optimal use of standard therapies and novel treatment options are needed to prevent early recurrence and metastases in these pts.

279 Background: Several therapies have recently gained regulatory approval in the United States (US) as second-line (2L) treatment options for patients with advanced unresectable or metastatic hepatocellular carcinoma (HCC). Treatment patterns and associated outcomes in a real-world population, especially in the contemporary era, remain understudied. Methods: This retrospective study utilized electronic health record data collected during routine patient care in outpatient oncology practices in the US. Adult patients diagnosed with advanced/ metastatic HCC between April 2017 and January 2020 were identified from the Concerto HealthAI database. Patients who survived at least one month from the end of first-line (1L) systemic therapy but did not initiate 2L therapy were classified as having received supportive care alone (SCA). Demographics, patient and disease characteristics, treatment patterns, and outcomes were described descriptively. Median overall survival (OS) from initiation of 2L therapy or end of 1L therapy for patients receiving SCA until death was estimated by the Kaplan-Meier method. Results: A total of 586 patients with advanced/ metastatic HCC were identified in the database. 330 patients received 1L therapy, and of those patients 63% (N= 207) received systemic 2L therapy (n= 105) or SCA (n= 102). At first diagnosis of advanced/ metastatic HCC, the median age was 64 years, and 86% were male. Of patients with ECOG status available at diagnosis (67%), 45% had ECOG status 0-1. The most common 1L agents prescribed were sorafenib (n= 126, 61%), lenvatinib (n= 28,14%) and sorafenib + nivolumab (n= 13, 6%) The most frequent agents prescribed in 2L were nivolumab (n= 44, 42%), sorafenib (n=18,17%), and lenvatinib (n=9, 9%). The median OS of patients receiving any systemic 2L therapy was 7.7 months (95% confidence interval 5.7-11.1) from time of receiving 2L therapy, whereas the median OS of patients receiving SCA was 5.0 months (95% confidence interval 3.3-7.1) from time of end of 1L therapy. Conclusions: In this contemporary national real-world cohort of patients with advanced/ metastatic HCC, a third of patients who received 1L therapy subsequently received 2L therapy. Next steps include investigating factors associated with non-receipt of 2L therapy, sequencing of therapies when multiple lines of therapies are received, and evaluating outcomes by type of agent received in 2L and beyond.

Objectives Current research on the perceptions of overdiagnosis or overdetection of breast cancer has largely been conducted outside of the USA and with women younger than 70 years. Therefore, we explored older women’s perceptions about the concept of overdetection of breast cancer and its influence on future screening intentions. Design Mixed-methods analysis using purposive sampling based on race/ethnicity, age and educational level. Semistructured interviews, including two hypothetical scenarios illustrating benefits and harms of screening and overdetection, were analysed using inductive and deductive thematic approaches. An inferential clustering technique was used to assess overall patterns in narrative content by sociodemographic characteristics, personal screening preferences or understanding of overdetection. Setting Houston/Galveston, Texas, USA. Participants 59 English-speaking women aged 70 years and older with no prior history of breast cancer. Results Very few women were familiar with the concept of overdetection and overtreatment. After the scenarios were presented, half of the women still demonstrated a lack of understanding of the concept of overdetection. Many women expressed suspicion of the concept, equating it to rationing. Women who showed understanding of overdetection were more likely to express an intent to discontinue screening, although 86% of the women stated that hearing about overdetection did not influence their screening decision. Themes identified did not differ by race/ethnicity, education, age or screening preferences. Differences were identified between women who understood overdetection and women who did not (r=0.23, p Conclusions Many older women did not understand the concept of overdetection, in addition to being suspicious of or resistant to the concept. Providing older women with descriptions of overdetection may not be sufficient to influence screening intentions.

Aim: To develop a claims-based prediction model of poor performance status (PS) in commercially insured and Medicare supplemental beneficiaries with cancer. Patients & methods: Retrospective analysis was conducted of electronic medical records (EMR) from community oncology practices linked to MarketScan claims. Multivariable logistic regression predicted PS scores from the EMR using claims-based diagnostic and procedure codes. Results: The study included 8442 patients diagnosed with cancer from 2007 to 2015. Overall, 8.1% of patients had poor EMR-based PS. Bootstrapping results from the final model showed sensitivity and specificity of approximately 75% with a predicted probability cutpoint = 0.078, c-statistic = 0.821 and pseudo-R 2 = 0.25. Conclusion: Patients with poor PS can be identified in claims data. This prediction model enables future studies evaluating cancer treatments and outcomes to account for PS.

Objective and background Minimally invasive breast biopsy (MIBB) rates remain well below guideline recommendations of more than 90% and vary across geographic areas. Our aim was to determine the variation in use attributable to the surgeon and facility and determine the patient, surgeon, and facility characteristics associated with the use of MIBB. Methods We used 100% Texas Medicare claims data (2000-2008) to identify women older than 66 years with a breast biopsy (open or minimally invasive) and subsequent breast cancer diagnosis/operation within 1 year. The percentage of patients undergoing MIBB as the first diagnostic modality was estimated for each surgeon and facility. Three-level hierarchical generalized linear models (patients clustered within surgeons within facilities) were used to evaluate variation in MIBB use. Results A total of 22,711 patients underwent a breast cancer operation by 1226 surgeons at 525 facilities. MIBB was the initial diagnostic modality in 62.4% of cases. Only 7.0% of facilities and 12.9% of surgeons used MIBB for more than 90% of patients. In 3-level models adjusted for patient characteristics, the percentage of patients who received MIBB ranged from 7.5% to 96.0% across facilities (mean = 50.1%, median = 49.2%) and from 8.0% to 87.0% across surgeons (mean = 50.3%, median = 50.9%). The variance in MIBB use was attributable to facility (8.8%) and surgeon (15.4%) characteristics. Lower surgeon and facility volume, longer surgeon years in practice, and smaller facility bed size were associated with lower rates of MIBB use. Conclusions Identification of surgeon and facility characteristics associated with low use of MIBB provides potential targets for interventions to improve MIBB rates and decrease variation in use. Type of study Retrospective cohort.

The decision regarding elective cholecystectomy in older patients with symptomatic cholelithiasis is complicated. We developed and validated a prognostic nomogram to guide shared decision making for these patients.We used Medicare claims (1996-2005) to identify the first episode of symptomatic cholelithiasis in patients older than 65 years who did not undergo hospitalization or elective cholecystectomy within 2.5 months of the episode. We described current patterns of care and modeled their risk of emergent gallstone-related hospitalization or cholecystectomy at 2 years. Model discrimination and calibration were assessed using a random split sample of patients.We identified 92,436 patients who presented to the emergency department (8.3%) or physician's office (91.7%) and who were not immediately admitted. The diagnosis for the initial episode was biliary colic/dyskinesia (65.3%), acute cholecystitis (26.6%), choledocholithiasis (5.7%), or gallstone pancreatitis (2.4%). The 2-year emergent gallstone-related hospitalization rate was 11.1%, with associated in-hospital morbidity and mortality rates of 56.5% and 6.5%. Factors associated with gallstone-related acute hospitalization included male sex, increased age, fewer comorbid conditions, complicated biliary disease on initial presentation, and initial presentation to the emergency department. Our model was well calibrated and identified 51% of patients with a risk less than 10% for 2-year complications and 5.4% with a risk more than 40% (C statistic, 0.69; 95% confidence interval, 0.63-0.75).Surgeons can use this prognostic nomogram to accurately provide patients with their 2-year risk of developing gallstone-related complications, allowing patients and physicians to make informed decisions in the context of their symptom severity and its impact on their quality of life.

KRAS (Kirsten Rat Sarcoma) is the most common oncogenic mutation detected in patients with non-small cell lung cancer (NSCLC). However, the role of KRAS as either a prognostic factor or predictive factor (modifier of treatment effects) in NSCLC is not well established at this time. This systematic literature review (SLR) and meta-analysis synthesized the available evidence regarding the role of KRAS mutation as a predictive factor and/or prognostic factor of survival and response outcomes in patients with advanced/metastatic (stage IIIB-IV) NSCLC. Relevant clinical trials and observational studies were identified by searching MEDLINE, Embase and Cochrane Register of Controlled Trials. Meta-analyses were performed using data extracted from multivariable and univariable analyses from clinical studies to assess the empirical evidence of KRAS mutation status as a prognostic or/and predicitive factor. 43 selected studies were identified by the SLR and included in this meta-analysis. Pairwise meta-analyses of hazard ratios (HRs) reported in randomized controlled trials (RCTs) did not demonstrate a significant prognostic effect of mutant KRAS on overall survival (OS) (HR=1.10; 95% CI [0.88, 1.38]) or progression free survival (PFS) (HR=1.03; 95% CI [0.80, 1.33]). However, when conducting meta-analyses on HRs reported in observational studies, a statistically significant negative prognostic effect of mutant KRAS was observed (OS HR=1.71; 95% CI [1.07, 2.84]; PFS HR=1.18; 95% CI [1.02, 1.36]). Meta-analyses of objective response rate (ORR) in RCTs demonstrated a negative prognostic effect of mutant KRAS (RR=0.38; 95% CI [0.16, 0.63]). Limited data were available to evaluate the role of KRAS mutation as a predictive factor. In conclusion, this research offers evidence that KRAS mutation may be a negative prognostic factor for survival and response outcomes in patients with advanced/metastatic NSCLC, but further research is needed to address conflicting results on the importance of KRAS mutations as a predictive factor.

There is a paucity of data on the current management and outcomes of liver-directed therapy (LDT) in older patients presenting with stage IV colorectal cancer (CRC). The aim of the study was to evaluate treatment patterns and outcomes in use of LDT in the setting of improved chemotherapy.We used Cancer Registry and linked Medicare claims to identify patients aged ≥66 y undergoing surgical resection of the primary tumor and chemotherapy after presenting with stage IV CRC (2001-2007). LDT was defined as liver resection and/or ablation-embolization.We identified 5500 patients. LDT was used in 34.9% of patients; liver resection was performed in 1686 patients (30.7%), and ablation-embolization in 554 patients (10.1%), with 322 patients having both resection and ablation-embolization. Use of LDT was negatively associated with increasing year of diagnosis (odds ratio [OR] = 0.96, 95% confidence interval [CI] 0.93-0.99), age85 y (OR = 0.61, 95% CI 0.45-0.82), and poor tumor differentiation (OR = 0.73, 95% CI 0.64-0.83). LDT was associated with improved survival (median 28.4 versus 21.1 mo, P 0.0001); however, survival improved for all patients over time. We found a significant interaction between LDT and period of diagnosis and noted a greater survival improvement with LDT for those diagnosed in the late (2005-2007) period.Older patients with stage IV CRC are experiencing improved survival over time, independent of age, comorbidity, and use of LDT. However, many older patients deemed to be appropriate candidates for resection of the primary tumor and receipt of systemic chemotherapy did not receive LDT. Our data suggest that improved patient selection may be positively impacting outcomes. Early referral and optimal selection of patients for LDT has the potential to further improve survival in older patients presenting with advanced colorectal cancer.

Multimodality therapy with chemotherapy and operative resection is recommended for patients with locoregional pancreatic cancer but is not received by many patients.To evaluate patterns in the use and timing of chemotherapy and resection and factors associated with receipt of multimodality therapy in older patients with locoregional pancreatic cancer.We used Surveillance, Epidemiology, and End Results-linked Medicare data (1992-2007) to identify patients with locoregional pancreatic adenocarcinoma. Multimodality therapy was defined as receipt of both chemotherapy and pancreatic resection. Logistic regression was used to determine factors independently associated with receipt of multimodality therapy. Log-rank tests were used to identify differences in survival for patients stratified by type and timing of treatment.We identified 10,505 patients with pancreatic adenocarcinoma. 5,358 patients (51.0%) received either chemotherapy or surgery, with 1,166 patients (11.1%) receiving both modalities. Resection alone was performed in 1,138 patients (10.8%), and chemotherapy alone was given to 3,054 (29.1%) patients. In patients undergoing resection as the initial treatment modality, 49.4% never received chemotherapy; 97.4% of patients who underwent chemotherapy as the initial treatment modality never underwent resection. The use of multimodality therapy increased from 7.4% of patients in 1992-1995 to 13.8% of patients in 2004-2007 (P.0001). The 2-year survival was 41.0% for patients receiving multimodality therapy, 25.1% with resection alone, and 12.5% with chemotherapy alone (P.0001). Of the patients receiving multimodality therapy, chemotherapy was delivered in the adjuvant setting in 93.1% and in the neoadjuvant setting in 6.9%, with similar 2-year survival with either approach (neoadjuvant vs adjuvant, 46.9% vs 40.6%; P = .16). Year of diagnosis, white race, less comorbidity, and no vascular invasion were independently associated with receipt of multimodality therapy.Only half of older patients with locoregional pancreatic cancer receive any treatment, and fewer than one quarter of treated patients receive multimodality therapy. Nearly all patients receiving chemotherapy as the initial treatment modality did not undergo resection, whereas half of those undergoing resection first received chemotherapy. When multimodality therapy is used, the vast majority of patients had chemotherapy in the adjuvant setting with a similar survival, regardless of approach.

Our objective was to determine the probability threshold for recurrent symptoms at which elective cholecystectomy compared to observation in older patients with symptomatic cholelithiasis is the more effective and cost-effective option. We built a decision model of elective cholecystectomy versus observation in patients >65 presenting with initial episodes of symptomatic cholelithiasis that did not require initial hospitalization or cholecystectomy. Probabilities for subsequent hospitalization, emergency cholecystectomy, and perioperative complications were based on previously published probabilities from a 5 % national sample of Medicare patients. Costs were estimated from Medicare reimbursements and from the Healthcare Cost and Utilization Project. Utilities (quality-adjusted life years, QALYs) were obtained from established literature estimates. Elective cholecystectomy compared to observation in all patients was associated with lower effectiveness (−0.10 QALYs) and had an increased cost of $3,422.83 per patient at 2-year follow-up. Elective cholecystectomy became the more effective option when the likelihood for continued symptoms exceeded 45.3 %. Elective cholecystectomy was both more effective and less costly when the probability for continued symptoms exceeded 82.7 %. An individualized shared decision-making strategy based on these data can increase elective cholecystectomy rates in patients at high risk for recurrent symptoms and minimize unnecessary cholecystectomy for patients unlikely to benefit.

Date Presented 04/06/19 Motion tracking sensors were added to a commercial SaeboGlove, enabling patients to engage in manual practice of instrumental activities of daily living in a computer-generated virtual world. Sensor-derived performance in completing functional tasks in the virtual environment was compared to real-world performance assessed using gold-standard measures. Statistical analysis of data collected during use by 15 stroke patients confirms the concurrent validity of the computer-generated measures. Primary Author and Speaker: Allison Ellington Additional Authors and Speakers: Richard Adams Contributing Authors: Kate Armstead, Kristen Sheffield, Heather Standish

2035 Background: BM in NSCLC pts are associated with significant morbidity and mortality. This analysis describes the frequency and timing of BM development, pt characteristics, systemic txs, and OS in NSCLC pts with and without BM. Methods: This retrospective observational study identified pts from the Flatiron-Foundation Medicine NSCLC Clinico-Genomic Database diagnosed from 1 Jan 2011 to 31 Oct 2017 with adv NSCLC and a tumor sample analyzed via FoundationOne. Tx pattern data were summarized by period (1 Jan 2011-1 Mar 2015; 2 Mar 2015-31 Dec 2017), therapy class (eg, anti-VEGF and EGFR, platinum-based), and BM occurrence. Descriptive statistics were used to summarize data; Chi-square and t-tests assessed statistically significant differences. OS was measured by site of met (BM only vs no-BM only vs BM and no-BM) via K-M methods from adv diagnosis until death or last activity date (censored). Results: Of 3257 pts, 1018/3257 (31.3%) had BM during follow-up; 726/1018 (71.3%) presented with BM within 30 days of adv diagnosis. The median age at adv diagnosis was 66.2 yrs. Relative to pts without BM, BM pts were younger, more likely to be female, of Asian descent, have stage IV disease, ≥2 met sites (including BM) at initial presentation, ≥3 met sites (including BM) during follow-up, and non-squamous histology (all p < 0.01). Approximately 78% (n = 2534) were treated with ≥1 systemic tx; platinum-based chemo-combinations were the most common 1st line tx, regardless of BM status. Increased use of PD-1/L1 tx was seen in 1st, 2nd, and 3rdline during the latter vs earlier period. No statistically significant difference in OS was observed in pts with BM only (17.1 mos; 95% CI 12.5-29.9), no-BM only (21 mos; 95% CI 19.4-22.8), or BM and no-BM (20.4 mos; 95% CI 18.9-23.3) (log rank p = 0.3027). Conclusions: In met NSCLC pts with a tumor sample that was molecularly profiled, OS was comparable, regardless of site(s) of disease; additional multivariate analyses including molecular profiles are needed. BM screening at initial diagnosis is important given the frequency in NSCLC. Future studies should assess whether the shift in systemic tx patterns impact the development and clinical outcomes.

2014 Background: Molecular alterations (MA) found in brain (Br) mets of NSCLC pts can differ from primary and/or other met sites, which may explain why therapies targeting primary tumors are less effective at preventing and treating intracranial disease. We analyzed the frequency of known driver genes in adv NSCLC pts and the association with overall survival (OS). Methods: This retrospective observational study identified pts from the Flatiron- Foundation Medicine NSCLC Clinico-Genomic Database who were diagnosed with adv NSCLC from 1 Jan 2011 to 31 Oct 2017 and had tumor tissue analyzed at any time following initial diagnosis via targeted DNA sequencing by FoundationOne. Descriptive statistics summarized MA from lung and met sites (Br and non-brain [NB]). OS was measured from adv diagnosis to death or last activity date (censored). Multivariable Cox proportional hazard regression model was used for time-to-event analysis. Results: Of 3257 pts, data were available from lung (n = 1621), Br (n = 180), and NB sites (n = 377): liver (n = 167), bone (n = 124), adrenal (n = 63), and spine (n = 23). Median age at adv diagnosis was 66.2 yrs. TP53(63.3%), KRAS(28.8%), EGFR(15.6%), STK11 (13.5%), and CDKN2A(8.5%) were frequently mutated genes in lung samples. Genes for Br vs NB sites included TP53(70.6%; 64.7%), KRAS(36.1%; 26.5%), EGFR (9.4%; 18.8%), STK11 (18.9%; 12.7%), and CDKN2A(6.1%; 10.1). KEAP1alterations were also present in 10% (Br), 7.4% (NB), and 6% of lung samples. In treated pts, lack of alterations in select genes ( STK11, TP53, KEAP1) was associated with longer OS, whereas lack of other alterations ( ARID1A, EGFR, ALK, ROS1) was associated with a shorter OS (p < 0.05). Patients with select mutations co-occurring with KRAS had higher risk of death compared to those with KRAS only (p < 0.05). Conclusions: Based on pts with NSCLC whose tumor tissue underwent DNA sequencing, the most frequently altered genes in lung and Br samples included TP53, KRAS, EGFR, STK11, and CDKN2A, with some being significantly associated with OS. Prognosis of NSCLC pts depends on clinical, demographic, and genomic factors and should be carefully considered to optimize clinical outcome.

Trends in the use of modern chemotherapeutic regimens, primary tumor resection, and the timing of chemotherapy and resection in older patients with stage IV colorectal cancer have not been evaluated. We used Cancer Registry- and Medicare-linked data (2000–2009) to describe time trends in resection of the primary tumor and receipt of chemotherapy in patients ≥66 presenting with stage IV colorectal cancer (N = 16,168). The mean age was 77.8 ± 7.3 years; 53.8 % were women and 82.9 % were white. Primary cancer sites were colon in 83.4 % and rectum in 16.6 %. Resection of the primary tumor decreased from 64.6 to 57.1 % (P

BACKGROUND A previous observational study reported that endoscopic ultrasound (EUS) is associated with improved survival in older patients with pancreatic cancer. The objective of this study was to reevaluate this association using different statistical methods to control for confounding and selection bias. METHODS Surveillance, Epidemiology, and End Results (SEER)-Medicare linked data (1992-2007) was used to identify patients with locoregional pancreatic cancer. Two-year survival in patients who did and did not receive EUS was compared by using standard Cox proportional hazards models, propensity score methodology, and instrumental variable analysis. RESULTS EUS was associated with improved survival in both unadjusted (hazard ratio [HR] = 0.67, 95% confidence interval [CI] = 0.63-0.72) and standard regression analyses (HR = 0.78, 95% CI = 0.73-0.84) which controlled for age, sex, race, marital status, tumor stage, SEER region, Charlson comorbidity, year of diagnosis, education, preoperative biliary stenting, chemotherapy, radiation, and pancreatic resection. Propensity score adjustment, matching, and stratification did not attenuate this survival benefit. In an instrumental variable analysis, the survival benefit was no longer observed (HR = 1.00, 95% CI = 0.73-1.36). CONCLUSIONS These results demonstrate the need to exercise caution in using administrative data to infer causal mortality benefits with diagnostic and/or treatment interventions in cancer research. Cancer 2013;119:3861–3869. © 2013 American Cancer Society.

Current guidelines recommend minimally invasive breast biopsy (MIBB) as the gold standard for the diagnosis of breast lesions. The purpose of this study was to describe geographic patterns and time trends in the use of MIBB in Texas.We used 100% Texas Medicare claims data (2000-2008) to identify women older than 66 years of age who underwent breast biopsy. Biopsies were classified as open or MIBB. Time trends, racial/ethnic variation, and geographic variation in the use of biopsy techniques were examined.A total of 87,165 breast biopsies were performed on 75,518 breast masses in 67,582 women; 65.8% of the initial biopsies were MIBB. Radiologists performed 70.3% and surgeons performed 26.2% of MIBB. Surgeons performed 94.2% of open biopsies. Hispanic women were less likely to undergo MIBB (55.9%) compared with white (66.6%) and black (68.9%) women (p0.0001). Women undergoing MIBB were also more likely to live in metropolitan areas and have higher income and educational levels (p0.0001). The rate of MIBB increased from 44.4% in 2001 to 79.1% in 2008 (p0.0001). There are clear geographic patterns in MIBB use, with highest use near major cities. Although rates are increasing overall, rates of improvement in the use of MIBB vary considerably across geographic regions and remain persistently low in more rural areas.Despite an increase in the use of MIBB over time, MIBB use was consistently lower than recommended. We must identify specific barriers in rural areas to effectively change practice and achieve the statewide goal of 90% MIBB.

Venous thromboembolic events after saphenous vein ablation procedures for varicose veins have been reported. Current knowledge of these events is based on single-institution studies or studies with small numbers of patients.The National Surgical Quality Improvement Program (NSQIP) database (2005-2009) was used to identify 3874 patients who underwent radiofrequency ablation (RFA) or endovenous laser ablation (EVLA) of the saphenous veins with or without stab phlebectomy. Outcome variables included documented postoperative deep vein thrombosis (DVT) or pulmonary embolism (PE). Bivariate and multivariate logistic regression analyses were performed to identify factors associated with venous thromboembolic events after ablation procedures.Procedures for lower extremity varicose veins included RFA in 2897 patients (74.8%) and EVLA in 977 (25.2%). Patients who underwent RFA were more likely to be older, obese, diabetic, hypertensive, and to have undergone procedures involving more than one vein (24% vs 4%; P .0001). Patients who underwent EVLA were more likely to have received general anesthesia (56.9% vs 40.8%; P .0001) and to have undergone concomitant stab phlebectomy (44.9% vs 31.7%; P .0001). The incidences of DVT (1.74% vs 1.52%; P = .63) and pulmonary embolus (0.07% vs 0%; P.99) were similar between EVLA and RFA. No significant predictors of DVT in the postoperative period were identified on bivariate or multivariate analyses. In the subgroup of 2514 patients who underwent ablation procedures without stab phlebectomy, those undergoing EVLA showed a trend toward a higher incidence of DVT (2.6% vs 1.4%; P = .057). After adjusting for patient demographics, DVT was 2.4 times more likely to develop in patients presenting with lower extremity ulcers than in those without ulcers (odds ratio, 2.4; 95% confidence interval, 1.01-6.11; P = .04). Although not statistically significant, the multivariate model found that when only ablation procedures were performed, EVLA was associated with an 83% increase in odds of DVT compared with RFA (odds ratio, 1.83; 95% confidence interval, 0.95-3.52; P = .06).The incidence of venous thromboembolic events after saphenous ablation is low. However, given that patients with lower extremity ulcers experienced an increased risk of DVT, care should be taken to ensure that the ablation catheter is positioned an appropriate distance from the saphenofemoral or sapheno-popliteal junction and that periprocedural preventative measures, such as anticoagulation prophylaxis, early ambulation, and lower extremity compression, are emphasized. The finding of a trend toward increased venous thromboembolic events in patients undergoing EVLA warrants further investigation in a large patient population.

To determine the frequency and predictors of cardiac stress testing before elective noncardiac surgery in Medicare patients with no indications for cardiovascular evaluation.The American College of Cardiology/American Heart Association guidelines indicate that patients without class I (American Heart Association high risk) or class II cardiac conditions (clinical risk factors) should not undergo cardiac stress testing before elective noncardiac, nonvascular surgery.We used 5% Medicare inpatient claims data (1996-2008) to identify patients aged ≥ 66 years who underwent elective general surgical, urological, or orthopedic procedures (N = 211,202). We examined the use of preoperative stress testing in the subset of patients with no diagnoses consistent with cardiac disease (N = 74,785). Bivariate and multivariate analyses were used to identify predictors of preoperative cardiac stress testing.Of the patients with no cardiac indications for preoperative stress testing, 3.75% (N = 2803) received stress testing in the 2 months before surgery. The rate of preoperative stress testing increased from 1.72% in 1996 to 6.44% in 2007 (P0.0001). A multivariate analysis adjusting for patient and hospital characteristics showed a significant increase in preoperative stress testing over time. Female sex [odds ratio (OR) 1.11; 95% CI: 1.02-1.21], presence of other comorbidities [OR 1.22; 95% confidence interval (CI): 1.09-1.35], high-risk procedure (OR 2.42; 95% CI: 2.04-2.89), and larger hospital size (OR 1.17; 95% CI: 1.03-1.32) were positive predictors of stress testing. Patients living in regions with greater Medicare expenditures (OR 1.24; 95% CI: 1.05-1.45) were also more likely to receive stress tests.In a 5% sample of Medicare claims data, 2803 patients underwent preoperative stress testing without any indications. When these results were applied to the entire Medicare population, we estimated that there are over 56,000 patients who underwent unnecessary preoperative stress testing. The rate of testing in patients without cardiac indications has increased significantly over time.

Obtaining cancer screening on patients with limited life expectancy has been proposed as a measure for low quality care for primary care physicians (PCPs). However, administrative data may underestimate life expectancy in patients who undergo screening.To determine the association between receipt of screening mammography or PSA and overall survival.Retrospective cohort study from 1/1/1999 to 12/31/2012. Receipt of screening was assessed for 2001-2002 and survival from 1/1/2003 to 12/31/2012. Life expectancy was estimated as of 1/1/03 using a validated algorithm, and was compared to actual survival for men and women, stratified by receipt of cancer screening.A 5 % sample of Medicare beneficiaries aged 69-90 years as of 1/1/2003 (n = 906,723).Receipt of screening mammography in 2001-2002 for women, or a screening PSA test in 2002 for men.Survival from 1/1/2003 through 12/31/2012.Subjects were stratified by life expectancy based on age and comorbidity. Within each stratum, the subjects with prior cancer screening had actual median survivals higher than those who were not screened, with differences ranging from 1.7 to 2.1 years for women and 0.9 to 1.1 years for men. In a Cox model, non-receipt of screening in women had an impact on survival (HR = 1.52; 95 % CI = 1.51, 1.54) similar in magnitude to a diagnosis of complicated diabetes or heart failure, and was comparable to uncomplicated diabetes or liver disease in men (HR = 1.23; 1.22, 1.25).Receipt of cancer screening is a powerful marker of health status that is not captured by comorbidity measures in administrative data. Because life expectancy algorithms using administrative data underestimate the life expectancy of patients who undergo screening, they can overestimate the problem of cancer screening in patients with limited life expectancy.

Depression has been associated with delayed presentation, inadequate treatment, and poor survival in patients with cancer.Using Surveillance, Epidemiology and End Results and Medicare linked data (1992-2005), we identified patients with pancreatic adenocarcinoma (N = 23,745). International classification of diseases, 9th edition, clinical modification codes were used to evaluate depression during the 3 to 27 months before the diagnosis of cancer. The effect of depression on receipt of therapy and survival was evaluated in univariate and multivariate models.Of patients with pancreatic cancer in our study, 7.9% had a diagnosis of depression (N = 1,868). Depression was associated with increased age, female sex, white race, single or widowed status, and advanced stage disease (P.0001). In an adjusted model, patients with locoregional disease and depression had 37% lower odds of undergoing surgical resection (odds ratio, 0.63; 95% confidence interval, 0.52-0.76). In patients with locoregional disease, depression was associated with lower 2-year survival (hazard ratio, 1.20; 95% confidence interval, 1.09-1.32). After adjusting for surgical resection, this association was attenuated (hazard ratio, 1.14; 95% confidence interval, 1.04-1.26). In patients who underwent surgical resection, depression was a significant predictor of survival (hazard ratio, 1.34; 95% confidence interval, 1.04-1.73). Patients with distant disease and depression had 21% lower odds of receiving chemotherapy (odds ratio, 0.79; 95% confidence interval, 0.70-0.90). After adjusting for chemotherapy for distant disease, depression was no longer a significant predictor of survival (hazard ratio, 1.03; 95% confidence interval, 0.97-1.09).The decreased survival associated with depression appears to be mediated by a lower likelihood of appropriate treatment in depressed patients. Accurate recognition and treatment of pancreatic cancer patients with depression may improve treatment rates and survival.

Controversy exists regarding the use of concurrent cholecystectomy during Roux-en-Y gastric bypass performed for morbid obesity.A decision model was developed to evaluate the cost-effectiveness of current strategies: routine concurrent cholecystectomy, Roux-en-Y gastric bypass alone with or without postoperative ursodiol therapy, and selective cholecystectomy based on preoperative findings on ultrasonography. Probabilities were obtained from a comprehensive literature review. Costs and hospital days were obtained from the Healthcare Cost and Utilization Project Nationwide Inpatient Sample. One-way sensitivity analyses were performed.The least expensive strategy was to perform RYGB alone without preoperative ultrasonography, with an average cost (over RYGB costs) of $537 per patient. RYGB with concurrent cholecystectomy had a cost of $631. Selective cholecystectomy based on preoperative ultrasonography was dominated by the other 2 strategies. Our model was most sensitive to the probability of developing gallbladder-related symptoms after RYGB alone. When the incidence of gallbladder-related symptoms was4.6%, the dominant strategy was to perform a RYGB alone without preoperative ultrasonography. For values6.9%, performing concurrent cholecystectomy at the time of the RYGB was superior to other strategies. When ursodiol was used, the least expensive strategy was to perform a concurrent cholecystectomy during RYGB.The main factor determining the most cost-effective strategy is the incidence of gallbladder-related symptoms after RYGB. The use of ursodiol was associated with an increase in cost that does not justify its use after RYGB. Finally, selective cholecystectomy based on preoperative ultrasonography was dominated by the other strategies in the scenarios evaluated.

Little is known about resource utilization (number of days in the hospital or medical care) between diagnosis and death in patients with pancreatic cancer.Using Surveillance, Epidemiology, and End Results (SEER)-Medicare linked data, we identified 25,476 patients with pancreatic cancer (1992-2005). Hospital and medical care days per person-month from the time of diagnosis were described, stratified by stage, treatment, and survival duration.Hospital/medical care days vary by length of survival and treatment strategy in patients with pancreatic cancer. For all stages, patients were in the hospital a mean of 6.4 days and received medical care a total of 9.0 days in the first month after diagnosis, decreasing to 1.7 and 3.7 days per month, respectively, by the end of the first year. Hospital/medical care days per month of life were higher in patients with shorter survival but increased sharply at the end of life in all patients, regardless of duration of survival. In patients with locoregional disease, resection was associated with a higher number of hospital/medical care days during the first 4 months after diagnosis, but fewer at the end of the first year. For distant disease, hospital days were similar but days in medical care were higher for patients receiving chemotherapy, increasing especially at the end of life.This study is the first to quantify hospital/medical care days in patients with pancreatic cancer by stage, treatment, and survival. This information will provide realistic expectations and allow for treatment decisions based on patient preferences.