Real-world treatment patterns and clinical outcomes for chemotherapy-based regimens in first-line MSI-H/dMMR metastatic colorectal cancer.

MICRO ABSTRACT: This retrospective observational study assessed real-world treatment patterns and clinical outcomes among first-line MSI-H/dMMR metastatic colorectal cancer patients. Of 150 patients in the study cohort, 38.7% were treated with chemotherapy and 61.3% with chemotherapy + EGFR/VEGF inhibitor (EGFRi/VEGFi). Clinical outcomes were better among patients who received chemotherapy + EGFR/VEGF inhibitor than those who received chemotherapy. INTRODUCTION: Prior to pembrolizumab approval in first-line (1L) treatment of MSI-H/dMMR metastatic colorectal cancer (mCRC), patients were managed with chemotherapy with or without an EGFRi or VEGFi, agnostic of biomarker testing or mutation status. This study assessed real-world treatment patterns and clinical outcomes among 1L MSI-H/dMMR mCRC patients treated with standard of care (SOC). PATIENTS AND METHODS: Retrospective observational evaluation of patients ≥18 years diagnosed with stage IV MSI-H/dMMR mCRC who received community-based oncology care. Eligible patients were identified (01-Jun-2017 - 29-Feb-2020) and followed longitudinally until 31-Aug-2020/the last patient record/date of death. Descriptive statistics and Kaplan-Meier analyses were conducted. RESULTS: Of 150 1L MSI-H/dMMR mCRC patients, 38.7% were treated with chemotherapy and 61.3% with chemotherapy + EGFRi/VEGFi. Accounting for censoring, the overall median real-world time to treatment discontinuation (95% CI) was 5.3 (4.4, 5.8) months; 3.0 (2.1, 4.4) and 6.2 (5.5, 7.6) months in the chemotherapy and chemotherapy + EGFRi/VEGFi cohorts, respectively. The combined median overall survival was 27.7 (23.2, not reached [NR]) months; 25.3 (14.5, NR) and 29.8 (23.2, NR) months in the chemotherapy and chemotherapy + EGFRi/VEGFi cohorts, respectively. The overall median real-world progression-free survival was 6.8 (5.3, 7.8) months; 4.2 (2.8, 6.1) and 7.7 (6.1, 10.2) months in the chemotherapy and chemotherapy + EGFRi/VEGFi cohorts, respectively. CONCLUSIONS: 1L MSI-H/dMMR mCRC patients receiving chemotherapy with EGFRi/VEGFi had better outcomes than those receiving only chemotherapy. An unmet need and opportunity to improve outcomes exists in this population that may be addressed by newer treatments like immunotherapies.

Adjuvant and neoadjuvant treatment patterns among resectable pancreatic cancer patients in the USA.

Aim: Chemotherapy is standard before and/or after pancreatic cancer resection, yet benefits of pre-resection chemotherapy are unclear. Real-world pre- and post-resection treatment patterns were evaluated retrospectively. Methods: Neoadjuvant (3-months pre-surgery) and adjuvant (6-months post-surgery) treatment claims from 1 January 2016 to 31 December 2019 in US adults with resectable pancreatic cancer were analyzed. Results: Of the 737 patients, 29% received no chemotherapy in either setting; 22% received chemotherapy in both settings. In the neoadjuvant and adjuvant settings, 69 and 33% of patients, respectively, received no treatment at all. FOLFIRINOX and gemcitabine monotherapy were the most common chemotherapies in the neoadjuvant and adjuvant settings, respectively. Adjuvant FOLFIRINOX increased post-2018, whereas gemcitabine-based regimens decreased. Conclusion: Several chemotherapy regimens were used in both settings. Treatment patterns differed between the two settings.

Some patients diagnosed with pancreatic cancer can undergo surgery to remove the tumor. Standard of care is to treat the patient with chemotherapy after the surgery. Chemotherapy is sometimes given before the surgery, yet it is unknown if this pre-treatment is beneficial. This study used insurance claim data from patients with pancreatic cancer in USA to evaluate real-world pre- and post-surgery chemotherapy patterns. Of the 737 analyzed patients, almost a third did not receive chemotherapy at all whereas one-fifth received chemotherapy both pre- and post-surgery. More patients received chemotherapy post-surgery than pre-surgery. Several different chemotherapy regimens were used, but the most common regimens used recently were those that had evidence from clinical trials. Chemotherapy was given more often to patients less than 65 years old than those 65 years or older, indicating more aggressive treatment in younger patients. Overall, the study indicates that a variety of treatments are being used and treatment patterns differ pre- and post-surgery. However, our study also shows that treatment strategies continue to evolve as our understanding of treatment impact and outcomes improves.

Systematic literature review and network meta-analysis of pembrolizumab versus other interventions for previously untreated, unresectable or metastatic, MSI-high or MMR-deficient CRC.

Aim: To compare pembrolizumab with competing interventions for previously untreated, unresectable or metastatic microsatellite instability-high or mismatch repair-deficient colorectal cancer. Method: Trials were identified via a systematic literature review and synthesized using a Bayesian network meta-analysis with time-varying hazard ratios (HRs). Results: Using intention-to-treat data, HRs for overall survival were generally in favor of pembrolizumab but not statistically significant; however, statistical significance was reached versus all comparators by month 16 when accounting for crossover. Estimated HRs for progression-free survival significantly favored pembrolizumab versus all comparators by month 12. Pembrolizumab was also superior to all comparators in terms of grade ≥3 adverse events. Conclusion: These analyses suggest that pembrolizumab is a highly efficacious and safe treatment in this population.

Experience of mismatch repair/microsatellite instability (MMR/MSI) testing among patients with advanced/metastatic colorectal cancer in the US.

Objective: We assessed knowledge and awareness of MMR/MSI testing among advanced/metastatic CRC patients in the US who had previously taken the test.Methods: A non-interventional, cross-sectional online survey was conducted among 150 US CRC patients invited through a research panel. Eligible patients had to be ≥18 years, with stage III or IV CRC (self-reported), had undergone MMR/MSI testing for CRC in past 12 months and could recall the test, and provided informed consent. Descriptive analyses were performed.Results: 81.3% of patients received MMR/MSI testing information from their doctor. Of 64.7% of patients who were a member of a patient support group, 86.6% received information from their groups. Most patients (82.7%) also searched for information on their own (internet searches). Most patients (93.5 to 96.9%) were satisfied with information received from these sources. Reasons for having testing done included increasing knowledge about their cancer (69.3%), being beneficial to determining treatment options (60.7%), and doctor recommendation (62.7%). Key barriers to testing included personal reservations regarding benefits of the test (29.3%), insurance coverage (27.3%), and out-of-pocket costs (18.7%); 45.3% reported no barriers.Conclusions: Patients were well informed about MMR/MSI testing. Increased education of testing benefits and addressing financial barriers may help to further improve testing rates.

Quantifying Unmet Need in Statin-Treated Hyperlipidemia Patients and the Potential Benefit of Further LDL-C Reduction Through an EHR-Based Retrospective Cohort Study.

BACKGROUND: Statins are effective in helping prevent cardiovascular disease (CVD). However, studies suggest that only 20%-64% of patients taking statins achieve reasonable low-density lipoprotein cholesterol (LDL-C) thresholds. On-treatment levels of LDL-C remain a key predictor of residual CVD event risk. OBJECTIVES: To (a) determine how many patients on statins achieved the therapeutic threshold of LDL-C < 100 mg per dL (general cohort) and < 70 mg per dL (secondary prevention cohort, or subcohort, with preexisting CVD); (b) estimate the number of potentially avoidable CVD events if the threshold were reached; and (c) forecast potential cost savings. METHODS: A retrospective, longitudinal cohort study using electronic health record data from the Indiana Network for Patient Care (INPC) was conducted. The INPC provides comprehensive information about patients in Indiana across health care organizations and care settings. Patients were aged > 45 years and seen between January 1, 2012, and October 31, 2016 (ensuring study of contemporary practice), were statin-naive for 12 months before the index date of initiating statin therapy, and had an LDL-C value recorded 6-18 months after the index date. Subsequent to descriptive cohort analysis, the theoretical CVD risk reduction achievable by reaching the threshold was calculated using Framingham Risk Score and Cholesterol Treatment Trialists' Collaboration formulas. Estimated potential cost savings used published first-year costs of CVD events, adjusted for inflation and discounted to the present day. RESULTS: Of the 89,267 patients initiating statins, 30,083 (33.7%) did not achieve the LDL-C threshold (subcohort: 58.1%). In both groups, not achieving the threshold was associated with patients who were female, black, and those who had reduced medication adherence. Higher levels of preventive aspirin use and antihypertensive treatment were associated with threshold achievement. In both cohorts, approximately 64% of patients above the threshold were within 30 mg per dL of the respective threshold. Adherence to statin therapy regimen, judged by a medication possession ratio of ≥ 80%, was 57.4% in the general cohort and 56.7% in the subcohort. Of the patients who adhered to therapy, 23.7% of the general cohort and 50.5% of the subcohort had LDL-C levels that did not meet the threshold. 10-year CVD event risk in the at-or-above threshold group was 22.78% (SD = 17.24%) in the general cohort and 29.56% (SD = 18.19%) in the subcohort. By reducing LDL-C to the threshold, a potential relative risk reduction of 14.8% in the general cohort could avoid 1,173 CVD events over 10 years (subcohort: 15.7% and 454 events). Given first-year inpatient and follow-up costs of $37,300 per CVD event, this risk reduction could save about $1,455 per patient treated to reach the threshold (subcohort: $1,902; 2017 U.S. dollars) over a 10-year period. CONCLUSIONS: Across multiple health care systems in Indiana, between 34% (general cohort) and 58% (secondary prevention cohort) of patients treated with statins did not achieve therapeutic LDL-C thresholds. Based on current CVD event risk and cost projections, such patients seem to be at increased risk and may represent an important and potentially preventable burden on health care costs. DISCLOSURES: Funding support for this study was provided by Merck (Kenilworth, NJ). Chase and Boggs are employed by Merck. Simpson is a consultant to Merck and Pfizer. The other authors have nothing to disclose.

Mismatch Repair/Microsatellite Instability Testing Practices among US Physicians Treating Patients with Advanced/Metastatic Colorectal Cancer.

The study objective was to assess US physicians' Mismatch Repair/Microsatellite Instability (MMR/MSI) testing practices for metastatic colorectal cancer (mCRC) patients. A non-interventional, cross-sectional online survey was conducted among 151 physicians (91 oncologists, 15 surgeons and 45 pathologists) treating mCRC patients in the US. Eligible physicians were US-based with at least 5 years of experience treating CRC patients, had at least one mCRC patient in their routine care in the past 6 months, and had ordered at least one MMR/MSI test for CRC in the past 6 months. Descriptive and logistic regression analyses were performed. Awareness of specific MMR/MSI testing guidelines was high (n = 127, 84.1%). Of those, 93.7% (119/127) physicians had awareness of specific published guidelines with majority 67.2% (80/119) being aware of National Comprehensive Cancer Network (NCCN) guidelines. Universal testing for all CRC patients was performed by 68.9% (104/151) physicians, while 29.8% (45/151) selectively order the test for some CRC patients. Key barriers for testing included insufficient tissue sample (48.3%, 73/151), patient declined to have the test done (35.8%, 54/151) and insurance cost concerns for patients (31.1%, 47/151), while 27.2% (41/151) reported no barriers. The survey demonstrated high awareness and compliance with MMR/MSI testing guidelines although universal testing rates seem to be suboptimal.

Antiplatelet Therapy and Clinical Outcomes Following Myocardial Infarction Among Patients in a U.S. Employer-Based Insurance Database.

BACKGROUND: Estimates of residual cardiovascular risks among patients who have experienced a recent acute myocardial infarction (MI) are predominantly derived from secondary prevention trial populations, patient registries, and population-based cohorts. OBJECTIVE: To generate real-world evidence of antiplatelet treatment and recurrent events following MI in patients on antiplatelet treatment among commercial, employer-based insured patients in a large administrative database. METHODS: This was a retrospective cohort claims database study using the Truven Health MarketScan Commercial Claims and Encounters and Medicare Supplemental databases between 2007-2011. Patients with an acute MI hospitalization with a discharge date between 2008 and 2010 were included. Excluded were those patients with documentation of stroke, transient ischemic attack (TIA), or severe bleeding at or before index hospitalization and with concomitant use of anticoagulant therapy following index hospitalization. Patients treated with clopidogrel following the index MI hospitalization were followed up to 1 year for repeat MI, stroke, and coronary revascularization. RESULTS: Among 33,943 post-MI continuous clopidogrel users without history of stroke, TIA, or bleeding, 22% had diabetes, whereas angina and renal impairment were less prevalent (5% and 7%, respectively). Over the 1-year follow-up, 2.4% experienced a repeat MI or stroke, and 8.2% underwent coronary revascularization. Angina, diabetes, and renal impairment were associated with elevated 1-year risk of repeat MI or stroke. CONCLUSIONS: This study suggests that there is residual cardiovascular risk, although relatively low, in an insured, secondary prevention population on antiplatelet treatment following an MI. In patients with MI, identifying angina, diabetes, and renal impairment may aid risk stratification and guide the effective management of these higher-risk patients. DISCLOSURES: Funding for this research was provided by Merck & Co. Although Merck & Co. formally reviewed a penultimate draft, the opinions expressed are those of the authorship and may not necessarily reflect those of the company. Reed Chase, Wu, Mavros, Heithoff, and Hanson are employees of Merck Sharp & Dohme, a subsidiary of Merck & Co., and may own stock and/or hold stock options in the company. Patel was an employee of Merck & Co. during the conduct of this study and preparation of the manuscript. Simpson is a paid consultant for Merck, Pfizer, and Amgen and has received speaker's fees from Merck and Pfizer. Study concept and design were contributed by all authors except Hanson. Heifhoff and Patel collected the data, and data interpretation was performed by Simpson, Mavros, Patel, Wu, and Hanson. The manuscript was written by Hanson, Mavros, and Patel and revised by Heithoff, Wu, Simpson, and Reed Chase.

State transition model: vorapaxar added to standard antiplatelet therapy to prevent thrombosis post myocardial infarction or peripheral artery disease.

OBJECTIVE: To evaluate long-term health benefits and risks of adding vorapaxar (VOR) to the standard care antiplatelet therapy (SC) of aspirin and/or clopidogrel, among a population with a recent myocardial infarction (MI) and/or peripheral artery disease (PAD). RESEARCH DESIGN AND METHODS: In a state-transition model, patients transition between health states (event-free, recurrent MI, stroke, death), while at risk of experiencing non-transition-related revascularization and non-fatal bleeding events. Risk equations developed from the TRA 2°P-TIMI 50 trial's patient-level data were used to predict cardiovascular (CV) outcomes over longer time horizons. Additional sources, including trials and US-based observational studies, informed the inputs for short-term CV risk, non-CV death, and health-related quality of life. Survival and quality-adjusted life-years (QALYs) were estimated over a lifetime horizon, discounted at 3% per year. RESULTS: Within a cohort of 7361 patients with recent MI and/or PAD, VOR + SC relative to SC alone yielded 176 fewer CV events (MIs, strokes, or CV deaths), but 27 more major bleeding events. VOR + SC was associated with increased life expectancy and health benefits (19.93 undiscounted life-years [LYs], 9.57 discounted QALYs vs. 19.61 undiscounted LYs, 9.41 discounted QALYs). The results were most sensitive to scenarios varying time of vorapaxar initiation, and the assumptions in the 90 day period post-MI. Additional analyses showed that add-on vorapaxar provides consistent incremental benefits in high-risk subgroups. CONCLUSION: This study contributes to the growing literature on secondary prevention add-on therapy, as results from these modeling analyses suggest that adding vorapaxar to SC for patients at high atherothrombotic risk can provide long-term health benefits.

Comparative Assessment of Medical Resource Use and Costs Associated with Patients with Symptomatic Peripheral Artery Disease in the United States.

BACKGROUND: There is growing concern about appropriate disease management for peripheral artery disease (PAD) because of the rapidly expanding population at risk for PAD and the high burden of illness associated with symptomatic PAD. A better understanding of the potential economic impact of symptomatic PAD relative to a matched control population may help improve care management for these patients. OBJECTIVE: To compare the medical resource utilization, costs, and medication use for patients with symptomatic PAD relative to a matched control population. METHODS: In this retrospective longitudinal analysis, the index date was the earliest date of a symptomatic PAD record (symptomatic PAD cohort) or any medical record (control cohort), and a period of 1 year pre-index and 3 years post-index was the study time frame. Symptomatic PAD patients and control patients (aged ≥ 18 years) enrolled in the MarketScan Commercial and Encounters database from January 1, 2006, to June 30, 2010, were identified. Symptomatic PAD was defined as having evidence of intermittent claudication (IC) and/or acute critical limb ischemia requiring medical intervention. Symptomatic PAD patients were selected using an algorithm comprising a combination of PAD-related ICD-9-CM diagnostic and diagnosis-related group codes, peripheral revascularization CPT-4 procedure codes, and IC medication National Drug Code numbers. Patients with stroke/transient ischemic attack, bleeding complications, or contraindications to antiplatelet therapy were excluded from the symptomatic PAD group but not the control group. A final 1:1 symptomatic PAD to control population with an exact match based on age, sex, index year, and Charlson Comorbidity Index (CCI) was identified. Descriptive statistics comparing patient demographics, comorbidities, medical resource utilization, cost, and medication use outcomes were generated. Generalized linear models were developed to compare the outcomes while controlling for residual difference in demographics, comorbidities, pre-index resource use, and pre-index costs. RESULTS: 3,965 symptomatic PAD and 3,965 control patients were matched. In both cohorts, 54.7% were male, with a mean age (SD) of 69.0 (12.9) years and a CCI score of 1.3 (0.9). Symptomatic PAD patients had more cardiovascular comorbidities than control patients (27.7% vs. 12.6% coronary artery disease, 27.1% vs. 15.9% hyperlipidemia, and 49.8% vs. 28.2% hypertension) in the pre-index period. Post-index rates of ischemic stroke, non-ST segment elevation myocardial infarction, unstable angina, and cardiovascular- or PAD-related procedures (limb amputations, endovascular procedures, open surgical procedures, percutaneous coronary intervention, and coronary artery bypass graft) were higher among symptomatic PAD patients versus control patients. All-cause annualized inpatient admissions (0.46 vs. 0.22 admissions), emergency department/urgent care days (0.27 vs. 0.22 days), and office visit days (12.5 vs. 10.2 days) were higher among symptomatic PAD versus control patients post-index. Annualized all-cause inpatient costs ($8,494 vs. $3,778); outpatient costs ($8,459 vs. $5,692); and total costs ($20,880 vs. $12,501) were higher among symptomatic PAD versus control patients post-index. Only 17.8% of symptomatic PAD patients versus 6.6% of control patients were on clopidogrel pre-index. In the post-index period, clopidogrel prescriptions in the symptomatic PAD population increased to 38.0%. Results were consistent in the regression models with the symptomatic PAD population having a higher number of all-cause post-index inpatient admissions, emergency department/urgent care days, office visit days, inpatient costs, outpatient costs, and total costs versus control patients (P ≤ 0.026). CONCLUSIONS: Symptomatic PAD patients have significantly higher medical resource use and costs when compared with a matched control population. As the prevalence of symptomatic PAD increases, there will be a significant impact on the population and health care system. The rates of use of evidence-based secondary prevention therapies, such as antiplatelet medication, were low. Therefore, greater effort must be made to increase utilization rates of appropriate treatments to determine if the negative economic and clinical impacts of symptomatic PAD can be minimized. DISCLOSURES: This study was funded by Merck & Co., Kenilworth, New Jersey. Chase and Heithoff are employees of Merck & Co., Kenilworth, New Jersey, and Upper Gwynedd, Pennsylvania. Friedman and Navaratnam are paid consultants for Merck & Co. Simpson is a paid consultant for Merck, Pfizer, and Amgen and has received speaker's fees from Merck and Pfizer. Study concept and design were contributed by Chase, Navaratnam, and Heilhoff, along with Simpson and Friedman. Friedman collected the data, which was interpreted by Simpson and Navaratnam, along with Friedman. The manuscript was written by Navaratnam and Friedman, along with Chase, Heilhoff and Simpson, and revised by all of the authors.

Resource use and costs in high-risk symptomatic peripheral artery disease patients with diabetes and prior acute coronary syndrome: a retrospective analysis.

OBJECTIVES: As the prevalence of peripheral artery disease (PAD) increases there is growing concern about the associated healthcare burden. This burden has not been well-characterized in high-risk patients with concurrent diabetes and/or acute coronary syndrome (ACS). The objective of this analysis was to assess comorbidities, medication use, outcomes, services and costs for 3 high-risk symptomatic PAD groups. METHODS: This retrospective longitudinal analysis used the MarketScan Commercial Claims and Encounters Database (2005-2013). The 3 high-risk symptomatic PAD groups were (1) symptomatic PAD with/without diabetes, (2) symptomatic PAD with/without prior ACS, and (3) symptomatic PAD with/without diabetes and prior ACS. The study time frame was a period of 1-year before the earliest date of a symptomatic PAD record and 3 years post. RESULTS: In all, 16,663 symptomatic PAD patients were identified across the three risk groups. Mean age ranged from 66.4-67.4 years; the majority (55.0%-63.3%) were men. At 3 years post index, patients with symptomatic PAD and a risk factor had significantly higher use of beta-blockers, ACE inhibitors and statins (P<0.0007), and higher rates of all-cause and symptomatic PAD-related medical services, diagnoses and procedures (P<0.05). Clopidogrel and statins were used by ≤ 41.2% and ≤ 66.7% of symptomatic PAD patients without risk, respectively, and ≤ 68.9% and ≤ 80.2% of patients with risks. All cause and symptomatic PAD-related treatment costs (P<0.0001) were higher for symptomatic PAD patients with risks versus patients without risks where annualized all-cause cost differences ranged from $7,482 to $13,504 and annualized PAD-related cost differences ranged from $605 to $1,997. CONCLUSIONS: Symptomatic PAD patients with diabetes and/or prior ACS have significantly higher medical resource use and costs compared to symptomatic PAD patients without these risk factors. The utilization rate of secondary prevention therapies is suboptimal; therefore, greater effort must be made to increase utilization and optimize treatment to minimize the impact of symptomatic PAD.