Impact of Dosing Frequency of Oral Oncolytics on Refill Adherence Among Patients with Hematological Malignancies

Background : With advances in oral oncolytics for hematologic malignancies, it is important to consider dosing frequency and treatment (tx) adherence, as prior data have shown poor adherence to oral cancer medications may result in inferior tx outcomes (Huang WC, Expert Rev Anticancer Ther, 2016; Muluneh B, J Oncol Pract, 2018). There is limited evidence regarding the impact of dosing frequency on tx adherence among patients with hematological malignancies treated with oral oncolytics. The objective of this study was to characterize real-world demographic and clinical characteristics, and compare refill adherence, among patients with hematological malignancies receiving once-daily (QD) versus twice-daily (BID) oral oncolytics. Methods : This retrospective cohort study used multi-year (2012-2020) commercial claims data from Optum's de-identified Clinformatics ® Data Mart Database and included adults (≥18 yr) with a diagnosis of a hematological malignancy identified using ICD-9-CM and ICD-10-CM codes. The exposure of interest was receipt of an oral oncolytic, and the date of the first observed oral oncolytic (QD or BID) was considered the index date. All patients were required to have continuous health plan enrollment for ≥6 mo prior and ≥6 mo after the index date. The 6-mo period prior to the index date was considered the baseline period for determining patient demographics, clinical characteristics, and prior medication use. To minimize the effect of the differences in observable baseline patient characteristics between the QD and BID groups on refill adherence, 1:1 propensity score (PS) matching was used. Tx refill adherence to QD and BID oral oncolytics was measured using two established metrics: proportion of days covered (PDC) and medication possession ratio (MPR). PDC, a conservative measure of refill adherence, was considered for primary analysis as it measures total days of drug coverage within a pre-specified follow-up period; whereas MPR which was included for sensitivity analysis, measures total drug supplied within the pre-specified follow-up period. PDC and MPR were measured at pre-defined time periods of 3 and 6 mo, and from the index date until the end of the follow-up period (variable-length follow-up). Patients with drug coverage for ≥80% (PDC or MPR ≥0.8) of pre-defined time periods were considered tx refill adherent. Results: The study identified 5,874 adults with hematological malignancies, of whom 4,938 (84.1%) received QD oral oncolytics and 936 (15.9%) received BID oral oncolytics. Before 1:1 PS matching, there were significant differences between the two groups in terms of mean age (67.5 yr QD vs 61.6 yr BID, P<0.001), insurance type (Medicare, 65.4% QD vs 46.8% BID, P<0.001), being previously untreated (67.6% QD vs 63.7% BID, P=0.019), and Charlson's comorbidity score (mean: 1.61 QD vs 1.44 BID, P<0.001). After 1:1 PS matching, demographics, baseline comorbidities, cancer histology, and line of therapy were well-balanced. The matched cohort comprised 936 patients receiving QD oral oncolytics and 936 patients receiving BID oral oncolytics. Table 1 summarizes refill adherence among patients with hematological malignancies receiving QD versus BID oral oncolytics. The proportion of patients with ≥80% of drug coverage during follow-up was higher for QD versus BID recipients at 3 mo: numerically higher by PDC (70.8% vs 66.9%, P=0.065) and statistically significantly higher by MPR (72% vs 67.8%, P=0.049). The proportion of adherent patients was significantly higher for QD vs BID for both PDC and MPR at 6 mo (PDC: 62% vs 56.8%, P=0.024; MPR: 62.7% vs 57.5%, P=0.021) and at variable-length follow-up (PDC: 82.4% QD vs 77.7% BID, P=0.011; MPR: 84.9% QD vs 80.9%, P=0.020). These results suggest QD dosing is associated with improved tx adherence to oral hematological oncolytics compared to BID dosing. Conclusions: This study demonstrates significantly higher refill adherence in patients receiving QD versus BID oral hematological oncolytics at 6 mo and variable-length follow-up, highlighting the potential benefit of dosing convenience in improving adherence to oral oncolytics in the real-world setting. As suboptimal tx adherence may result in reduced tx effectiveness, real-world characterization of refill adherence rates of oral oncolytics can better inform on tx effectiveness outside of a controlled clinical trial environment. Figure 1 Figure 1. Disclosures Challagulla: Pharmacyclics LLC, an AbbVie Company: Current Employment; AbbVie: Current equity holder in publicly-traded company. Kebede: Pharmacyclics LLC, an AbbVie Company: Consultancy; ObsEva: Other. Rege: Pharmacyclics LLC, an AbbVie Company (paid to institution): Consultancy. Volodarsky: AbbVie: Current equity holder in publicly-traded company; Pharmacyclics LLC, an AbbVie Company: Current Employment. Osei-Bonsu: AbbVie: Current equity holder in publicly-traded company; Pharmacyclics LLC, an AbbVie Company: Current Employment. Karve: AbbVie: Current Employment, Current equity holder in publicly-traded company.

Physician-pharmacy integration and oral cancer drug use and quality.

39 Background: Public reports suggest increasing integration of in-house specialty pharmacies by independent and system-based oncology practices. Understanding the impact of such integration has important implications for state-level regulations limiting physicians’ ability to launch pharmacies in certain states and policies governing pharmacy network design. In this analysis, I document the growth of in-house pharmacies and estimate the impact of this growth on oral cancer drug use and quality. Methods: I used 2006-2017 data from Medicare Fee-for-Service and Part D claims, pharmacy names and characteristics from health plan pharmacy network lists and the National Plan and Provider Enumeration System, and a unique Health System and Practice Dataset, developed by National Bureau of Economic Research and Harvard University researchers, that tracks practice ownership relationships. I first linked physician organizations and pharmacies that they operate using a novel claims-based algorithm combining information on pharmacy characteristics, similarities in names of practices and pharmacies, and the share of total pharmacy spending attributable to a single practice or system. I then used an event study approach to compare oral oncolytic use and quality at practices launching a pharmacy between 2009 to 2014 compared with matched controls. Outcomes included total spending on oral oncolytics, use of oral drugs when an intravenous equivalent exists (capecitabine and 5-fluoruracil), timeliness of new prescription fills (# days from first fill to last office visit), medication adherence, and early discontinuation of lenalidomide, tyrosine kinase inhibitors, aromatase inhibitors, tamoxifen, enzalutamide, and abiraterone. Results: The number of independent or system-based oncology practices with an in-house pharmacy filling any oncology prescriptions increased from 135 in 2006 to 442 in 2017. In that time, the share of Medicare Part D spending on oral oncolytics filled at in-house pharmacies increased from 4% in 2006 to 27% in 2017. The launch of an in-house pharmacy was not associated with an overall increase in spending on oral oncolytics, but was associated with a 4.5 percentage point (p =.01) increase in the use of capecitabine relative to 5-fluorouracil, within 2 years of launch. In-house pharmacies were associated with a modest decrease in the time to fill an initial prescription (2.4 days, p <.001) within 2 years of launch, but no improvements in adherence or reductions in early discontinuation. Conclusions: There has been substantial growth in the use of in-house pharmacies in oncology in recent years. Having an in-house pharmacy only had modest effects on cost and quality. Policymakers should therefore approach claims that in-house pharmacies meaningfully impact cost and quality with caution.

Improving oral oncolytic education in a safety-net outpatient hematology-oncology practice.

266 Background: Oral oncolytics (OO) offer convenient administration and reduce the burden of cancer treatment, while creating particular challenges regarding safety monitoring and adherence. A baseline review of oral oncolytic education (OOE) at our safety-net institution identified that none of the patients who started OO therapy from September to December 2019 had complete documentation of OOE and a care plan. This results in potential increased risk of toxicity, non-adherence to therapy, and poor adherence to follow-up schedule for lab monitoring, dose adjustment, and toxicity assessment. Therefore, we sought to increase the percentage of completed components of an OOE and care plan that are documented in the EHR prior to new oral oncolytic initiation to 60% over a 6-month period. Methods: A multidisciplinary Quality Training Program team consisting of 2 physicians, an oncology pharmacist, and an oncology RN specialist was created. With stakeholder engagement, we identified barriers to quality OOE and documentation, including: unfamiliarity of staff with ASCO-ONS standards, adoption of a new EMR, lack of standardized structure and documentation for OOE, and limited number of staff. PDSA cycle 1 defined RN role as staff in charge of oral oncolytic prior-auth, coordination, and education process, reinforced communication of providers with RNs, and defined the components of oral oncolytic education and care plan that meets QOPI & ASCO-ONS standards. PDSA cycle 2 implemented a new simplified workflow which included (1) EHR worksheet to document oral oncolytic education, (2) in-person RN teaching, (3) printed education materials, pill box, and thermometer, and (4) 1-week follow up calls. Results: Our baseline data revealed that only 55% of patients had any documentation of OOE. Content of documented OOE varied significantly with only a mean of 37% ASCO-ONS safety standards being documented. During PDSA cycle 1 documentation improved to a mean 54% standards, and with PDSA cycle 2 82% standards of an OOE documented. Overall documentation of OOE, increased to 83% by PDSA cycle 2. Symptom check 1-week follow-up calls increased from 22% at baseline to 78% after PDSA cycle 2. Conclusions: Over a 6-month period, we improved OOE and documentation by meeting our goal of increasing the number of documented components from 40% to 82%. Review of processes with stakeholders is imperative to practice improvement. Implementation of an EHR tool is an easy way to improve quality standardized OOE and has the potential to increase OO adherence and decrease toxicity.

Technology interventions to support adherence to oral oncolytic agents: A systematic review and meta-analysis.

320 Background: The increase in patients receiving oral oncolytics requires oncology health care professionals to have processes and interventions that support patient adherence. Because adherence to oral oncolytics is a priority for achieving optimal outcomes, the ASCO QOPI Standards emphasize the need to assess for adherence at meaningful intervals as well as implement interventions to promote adherence. Technology-based interventions have the potential to assess and support adherence. The objective of this review is to evaluate the overall effect of any technology-based intervention, as well as compare the use of interactive technology rather than non-interactive technology to improve oral oncolytic adherence. This review will serve as the evidence base for a clinical practice guideline on oral oncolytic adherence. Methods: A medical librarian searched EMBASE, PubMed, and CINAHL for comparative studies published in English from January 2000 to May 2021. Two reviewers screened titles and abstracts, and eligible full text articles independently and in duplicate using Covidence. When possible, quantitative findings were pooled in a meta-analysis. Risk of bias assessment for randomized controlled trials was done using the Cochrane Collaboration risk-of-bias 2.0 tool and for observational studies, the ROBINS-I instrument was used. The certainty of evidence was assessed using the GRADE (Grading of Recommendations Assessment, Development and Evaluation) approach. Results: Out of 663 studies, we identified 14 as eligible for analysis. Of the six RCTs (n = 737) that compared any technological intervention to no intervention, there was some heterogeneity across interventions (e.g., text messaging, mobile app, computer program) and reported outcome measures for adherence, including adherence rates, relative dose intensity (RDI), and number of weeks adherent. Patients using any technology rather than no technology may have higher adherence rates (MD: 8.81; 95% CI: 3.82, 13.81); however, there may be little effect on RDI (MD: -0.01; 95% CI: -0.04, 0.02) and number of weeks adherent (MD: -0.70; 95% CI: -1.96, 0.56), respectively. One RCT (n = 444) reported on adolescents receiving interactive and non-interactive interventions. There may be little effect on adherence rates among patients receiving interactive technology interventions rather than non-interactive education intervention (MD: 1.5; 95% CI, −0.2, 3.2). Conclusions: Better systems of oral oncolytic care are needed to support patients and their caregivers. Technology-based interventions may improve medication adherence in cancer patients on oral oncolytics; however, we are uncertain about the impact on other measure of adherence or the superiority of interactive rather than non-interactive technology interventions. Due to inconsistency in the evidence, additional research in this area is recommended.

Novel Tool to Monitor Adherence to Oral Oncolytics: A Pilot Study

PURPOSE Nonadherence is a significant issue in cancer care, especially as more oral therapies become available. Measuring and optimizing adherence to such therapies is challenging. In this study, we tested a novel technology that records real-time medication-taking behavior from a smart prescription bottle and can communicate with patients via text message to intervene in cases of nonadherence. METHODS We conducted a 28-patient pilot study to assess the feasibility of this technology in measuring and improving adherence in patients taking capecitabine, an oral chemotherapy agent with a complex, cyclical regimen. The study had a preintervention stage, during which patients were monitored, and an intervention stage, during which the text messaging intervention was enabled. RESULTS During preintervention, patients had an average self-adherence of 89%, and during post intervention, they had an average adherence of 90%. We defined three categories of patients by change in adherence: category 1 (> 8%), category 2 (−8% to 8%), and category 3 (< −8%). Patients in category 1 tended to live in regions with lower average household income (mean = $58,937 in US dollars [USD]) than those in category 2 (mean = $77,482 USD) and category 3 (mean = $90,972 USD). Of poststudy survey respondents, most indicated that they would want to continue using this technology and that they would recommend it to others. CONCLUSION This novel technology is able to monitor, measure, and intervene for patients taking capecitabine in real time. Adherence overall was high, and some patients appeared to benefit more from text-message interventions. Future work should focus on patients deemed high risk for nonadherence.

Five Year Analysis Assessing the Trend in Prescribing and Expenditures of Oral Oncolytics for Medicare Part D: 2013-2017

Introduction: Oral oncolytics are becoming a mainstay in oncology, representing first-line therapies for numerous different malignancies. In addition, the cost of oncology drugs has increased dramatically in recent years. Given the increasing number of oral oncolytics available, as well as the increase in medication costs in recent years, it is important to assess the trend in prescriptions and expenditures of these agents. Methods: A descriptive retrospective analysis of the Medicare Part D Provider Utilization and Payment Data Public Use File (PUF) was conducted for the years 2013 through 2017. Outcomes of interest included total aggregate prescriptions per year, total aggregate expenditures per year, mean expenditure per prescription per year, and mean expenditure per standardized 30-day prescription per year. Chi-square tests were conducted to assess statistical significance of differences in proportions of prescriptions as well as expenditures between 2013 and 2017. Results: The number of prescriptions for oral oncolytics dispensed to Medicare Part D beneficiaries increased from 7,017,902 in 2013 to 8,164,883 in 2017. Medicare Part D expenditures for oral oncolytics increased greater than 2.5-fold from $5,631,224,307 in 2013 to $14,422,681,331 in 2017 after adjusting for inflation. The mean expenditure per prescription for oral oncolytics increased from $802 in 2013 to $1,766 in 2017. Conclusions: This study found oral oncolytic utilization has been increasing in recent years with a slight, but statistically significant increase in the proportion of oncolytics for all Medicare prescriptions from 2013 through 2017.

The Use of Real-World Evidence for Oral Chemotherapies in Breast Cancer

Almost all patients with breast cancer will eventually receive chemotherapy drugs, the majority of which are administered as IV infusions. Real-world evidence indicates that while current treatment paradigms vary considerably from guideline recommendations, there is an increasing trend towards a preference for oral oncolytics among patients with breast cancer. Recent data have shown that oral anticancer therapeutics represent 25% of the oncology drug market share and that there is a high demand for these agents. Therefore, oral formulations of chemotherapy agents such as paclitaxel are currently under development. Although oral oncolytics are associated with several advantages over conventional intravenous drugs, maintaining adherence to therapy is a major barrier in achieving improved outcomes with these agents. Advanced practitioners can facilitate improved adherence to oral oncolytics by integrating evidence into practice to support better education and communication strategies to address patient concerns, overcome key hurdles, and ultimately, empower patients.

Providing uninterrupted oral oncolytic therapies during the COVID-19 pandemic.

226 Background: Uninterrupted utilization of oral oncolytics is critical to maximizing safety and efficacy of cancer treatment. The COVID-19 pandemic presented numerous challenges to delivering a continuous and safe supply of oral oncolytics to patients with cancer including potential loss of insurance coverage, patient lost income making copays more difficult, remote pharmacy staffing difficulties, and logistical challenges in safely distributing drug to cancer patients. Tennessee Oncology has an in-house Specialty Pharmacy that utilizes home delivery of oral oncolytics while coordinating care with providers during changing patient situations. Methods: We analyzed patients who received an oral oncolytic from our pharmacy in two periods: January-May 2019 and January-May 2020. We compared the aggregate patient copay amounts during these periods, the number of patients who utilized copay assistance or foundational financial support. For insights on continuation we also assessed the medication possession ratios (MPR, the sum of the day’s supply for all fills of a given drug in a particular period divided by the number of days in that period) during these time periods for five of our most commonly dispensed drugs. Results: The aggregate patient copay was similar between the two time periods. A 22% increase in the utilization of copay cards indicated patient’s insurance coverage was sustained. We also observed a 12% increase in the number of patients utilizing foundation support for prescriptions filled. MPRs for five commonly dispensed oral oncolytics were unchanged during COVID-19. Conclusions: Our in-house specialty pharmacy maintained delivery of oral oncolytics during the COVID-19 pandemic. Patient cost share was contained by our pharmacy staff proactively utilizing copay cards for all eligible patients and diligently securing foundational grant support. The pharmacy interventions allowed for affordability, uninterrupted pharmacy operations, and consistent medication supply. This led to continued medication adherence. MPR for the 5 top dispensed medications was consistent in a year-on-year comparison. [Table: see text]

The effects of COVID-19 on new oral oncolytic treatments.

102 Background: Dependable and timely dispensing and delivery of oral oncolytics to patients with a new indication for therapy is a central part of modern cancer care. The COVID-19 pandemic has presented numerous impediments and challenges to patients receiving oral therapy from many specialty pharmacies in a timely due to remote pharmacy staffing and drug shipment. Tennessee Oncology has an integrated URAC and ACHC accredited Specialty Pharmacy to ensure the seamless care for our patients prescribed oral oncolytics. We investigated the effect of COVID-19 on the number of patients initiating care with an oral oncolytic and the time to fill during the pandemic. Methods: We analyzed the number of overall new patients to the practice and new patients receiving oral oncolytics in two year-to-year comparisons: (1) January-March 2019 vs. January-March 2020 and (2) April-May 2019 vs. April-May 2020. We then compared the average pharmacy turnaround time (defined as the time of entry of a regimen in the electronic medical record that contained an oral oncolytic until the time that prescription was ready for shipment) and the average time from regimen entry until the patient received that medication. Prescriptions received and filled on the day of order entry were recorded as a one-day turnaround time. Results: A year to year increase of 7% in practice new-patient volume was associated with a 13% increase in new oral oncolytic patients from January-March 2020. Year to year April and May comparisons, noted a 33% decrease in new-patient volume to our practice with an associated 10% decrease in new oral oncolytic patients. Time to fill remained consistent in March and April 2020 at 1.84 days vs. 1.78 for 2019. The time from regimen entry to patient shipment receipt was also stable year to year (3.10 vs. 3.06 days). Conclusions: Our in-house Specialty Pharmacy was able to continue delivery of new prescriptions for oral oncolytics during the COVID-19 pandemic. There was a fall in the number of new patient dispensing in April-May 2020 that we attribute to a decrease in cancer diagnoses related to COVID-19 as reflected by a fall in total practice new patients. New patient on-boarding activities including prior authorizations, co-pay assistance, patient education were maintained and the measured time to fill from regimen entry to patient receipt were unchanged.