Oral Anticancer Therapies Research Articles

Implementing a drug interaction protocol for oral systemic anti-cancer therapy with focus on CDK4/6 inhibitors.

302 Background: Oral anti-cancer therapies (OACTs) are being increasingly used. Despite their convenience, OACTs introduce challenges with adherence, prescribing errors, and high incidence of drug-drug interactions (DDIs). Currently, there are limited guidelines for DDI checking. Cyclin-dependent kinase 4/6 inhibitors (CDK4/6i) have revolutionized the management of metastatic ER+/HER2- breast cancer. While an overall survival benefit has been demonstrated with Ribociclib, its use can be problematic due to frequent DDIs and the risk of QTc prolongation. DDIs are routinely checked in our center with two interaction checkers, but they are not always documented due to a lack of a standardized protocol. This study aims to evaluate current DDI checking practices, identify common DDIs, and implement a systematic DDI protocol. Methods: A retrospective review was conducted on patients (pts) prescribed CDK4/6i in our center from Jan 2023 to Apr 2024. Data on pt demographics, treatment, DDI documentation, toxicity, and survival were collected. Retrospective DDI checks using Lexi-Interact and Drugs.com were performed. Results: A total of 65 pts were included, with 38 on Ribociclib and 27 on Palbociclib. The median follow-up was 11.6 months (range: 1-71). The median age of pts on Ribociclib was 54 (range: 35-77), compared to 61 (range: 44-82) on Palbociclib. The median number of medications was three with Ribociclib and five with Palbociclib. Seven pts (26%) were prescribed Palbociclib due to contraindications to Ribociclib, including cardiac disease (n=2), QTc-prolonging medications (n=4), and advanced age (n=1). DDI checks were documented in 46% of Ribociclib and 14% of Palbociclib pts (p=0.0063). There was a weak negative correlation between DDI documentation and toxicity, stronger in the Palbociclib arm (-0.079 for Ribociclib vs. -0.335 for Palbociclib). Retrospective checks revealed DDIs in 50% of Ribociclib and 52% of Palbociclib pts. Major DDIs were identified in 21% of Ribociclib and 7% of Palbociclib pts (p=0.133). Common major DDIs involved opioids and QTc-prolonging medications, most frequently antidepressants. Grade ≥3 toxicity occurred in 49% of Ribociclib vs. 64% of Palbociclib pts (p=0.21). Ribociclib caused more rash, liver toxicity, and diarrhea, while Palbociclib had significantly more grade ≥3 neutropenia (48% vs. 21%, p=0.042). No QTc prolongation was observed. Dose reductions were more common with Palbociclib (48% vs. 32%, p=0.27). There was no significant difference in survival data. Conclusions: Our findings highlight the importance of systematic DDI checks in pts receiving OACTs. Implementing a standardized protocol could reduce adverse interactions and improve pt outcomes. Further studies are needed to validate these findings and develop DDI guidelines. A standardized DDI protocol has now been developed for our center, with plans to re-audit after implementation.

Harnessing the Power of Implementation Science to Improve the Quality of Care for Oral Anticancer Therapies.

Harnessing the Power of Implementation Science to Improve the Quality of Care for Oral Anticancer Therapies.

Effect of 5-Aminolevulinic Acid (5-ALA) in "ALADENT" Gel Formulation and Photodynamic Therapy (PDT) against Human Oral and Pancreatic Cancers.

Oral squamous-cell and pancreatic carcinomas are aggressive cancers with a poor outcome. Photodynamic therapy (PDT) consists of the use of photosensitizer-induced cell and tissue damage that is activated by exposure to visible light. PDT selectively acts on cancer cells, which have an accumulation of photosensitizer superior to that of the normal surrounding tissues. 5-aminolevulinic acid (5-ALA) induces the production of protoporphyrin IX (PpIX), an endogenous photosensitizer activated in PDT. This study aimed to test the effect of a new gel containing 5% v/v 5-ALA (ALAD-PDT) on human oral CAL-27 and pancreatic CAPAN-2 cancer cell lines. The cell lines were incubated in low concentrations of ALAD-PDT (0.05%, 0.10%, 0.20%, 0.40%, 0.75%, 1.0%) for 4 h or 8 h, and then irradiated for 7 min with 630 nm RED light. The cytotoxic effects of ALAD-PDT were measured using the MTS assay. Apoptosis, cell cycle, and ROS assays were performed using flow cytometry. PpIX accumulation was measured using a spectrofluorometer after 10 min and 24 and 48 h of treatment. The viability was extremely reduced at all concentrations, at 4 h for CAPAN-2 and at 8 h for CAL-27. ALAD-PDT induced marked apoptosis rates in both oral and pancreatic cancer cells. Elevated ROS production and appreciable levels of PpIX were detected in both cell lines. The use of ALA-PDT as a topical or intralesional therapy would permit the use of very low doses to achieve effective results and minimize side effects. ALAD-PDT has the potential to play a significant role in complex oral and pancreatic anticancer therapies.

Creating a national model to build anti-cancer stewardship and quality improvement initiatives.

e23219 Background: The Department of Veterans Affairs (VA) Pharmacy Benefits Management (PBM) Services created a national stewardship with focus on anti-cancer therapeutics within a disease-specific cohort. Building a model to focus on Veterans with a common malignancy is a novel approach. A toolkit was built containing resources to support initiatives to promote standardization of practice and monitor outcomes as a continual quality improvement process. This model was piloted in Veteran patients with Chronic Myeloid Leukemia (CML) since Tyrosine Kinase Inhibitors (TKIs) account for the second highest utilization among outpatient oral anti-cancer therapies in VA . Methods: Business rules identified Veterans Integrated Service Network (VISN) CML cohorts by using data and diagnostic coding (ICD-10; SNOMED CT) from the VA Electronic Health Record (EHR): primary care and hematology/oncology visits, inpatient stays, and problem lists. Medication Use Evaluations (MUEs) were developed: MUE #1: Veterans who received a drug other than imatinib as their initial VA prescription If new initiation, documented reason(s) for drug selection If continuation, prior drug therapy history MUE #2: Veterans who switched from first to second-line TKI Documented reason(s) for switch to 2L Documentation of adverse drug reaction (ADR) in the EHR. Results: 16 VISNs participated in the MUEs. Patient counts are each ~25% of the total CML cohort; ~50% of patients received imatinib 1L and have not switched to 2L. Responses for MUE #1 (N = 559) 293 (52%) continued therapy originally started outside VA with 71% of these patients (n = 208) without documentation of prior imatinib 266 (48%) newly initiated therapy with top documented reasons Intermediate/high risk scoring: 109 (41%) Reason not documented: 80 (30%) Cited FDA indication for CML without clinical justification: 35 (13%) Responses for MUE #2 (N = 576) Top documented reasons for switch from 1L to 2L therapy ADR: 325 (56%) Resistance / inadequate response: 132 (23%) Disease progression: 117 (20%) Only 59 (18%) who experienced an ADR had it documented in the EHR allergies / adverse reactions section. Conclusions: Disease-focused oncology stewardship in a national healthcare system is feasible. Imatinib remains the preferred TKI and accounts for the highest utilization. Oncology Stewardship activities based on the results include education on disease coding, an educational document on why to use imatinib in the 1L setting, and a medication safety article to emphasize documentation of ADRs. In our 1L to 2L MUE, ADRs were the most common reason for patients to be switched to 2L. Future activities include an education sheet on managing TKI ADRs and criteria for a potential treatment-free remission. Further interventions in TKI prescribing may be instituted in select sites. Following initiatives for CML, Anti-Cancer Stewardship Program will be expanded to other oncologic diseases.

A pharmacist-led interprofessional medication adherence program improved adherence to oral anticancer therapies: The OpTAT randomized controlled trial.

Oral anticancer therapies such as protein kinase inhibitors (PKIs) are increasingly prescribed in cancer care. We aimed to evaluate the impact of a pharmacist-led interprofessional medication adherence program (IMAP) on patient implementation (dosing history), persistence (time until premature cessation of the treatment) and adherence to 27 PKIs prescribed for various solid cancers, as well as the impact on patients' beliefs about medicines (BAM) and quality of life (QoL). Patients (n = 118) were randomized 1:1 into two arms. In the intervention arm, pharmacists supported patient adherence through monthly electronic and motivational feedback, including educational, behavioral and affective components, for 12 months. The control arm received standard care plus EM without intervention. All PKIs were delivered in electronic monitors (EMs). Medication implementation and adherence were compared between groups using generalized estimating equation models, in which relevant covariables were included; persistence was compared with Kaplan‒Meier curves. Information on all treatment interruptions was compiled for the analysis. Questionnaires to evaluate BAM and QoL were completed among patients who refused and those who accepted to participate at inclusion, 6 and 12 months post-inclusion or at study exit. Day-by-day PKI implementation was consistently higher and statistically significant in the intervention arm (n = 58) than in the control arm (n = 60), with 98.1% and 95.0% (Δ3.1%, 95% confidence interval (CI) of the difference 2.5%; 3.7%) implementation at 6 months, respectively. The probabilities of persistence and adherence were not different between groups, and no difference was found between groups for BAM and QoL scores. No difference in BAM or QoL was found among patients who refused versus those who participated. The intervention benefited mostly men (at 6 months, Δ4.7%, 95% CI 3.4%; 6.0%), those younger than 60 years (Δ4.0%, 95% CI 3.1%; 4.9%), those who had initiated PKI more than 60 days ago before inclusion (Δ4.5%, 95% CI 3.6%; 5.4%), patients without metastasis (Δ4.5%, 95% CI 3.4%; 5.7%), those who were diagnosed with metastasis more than 2 years ago (Δ5.3%, 95% CI 4.3%; 6.4%) and those who had never used any adherence tool before inclusion (Δ3.8%, 95% CI 3.1%; 4.5%). The IMAP, led by pharmacists in the context of an interprofessional collaborative practice, supported adherence, specifically implementation, to PKIs among patients with solid cancers. To manage adverse drug events, PKI transient interruptions are often mandated as part of a strategy for treatment and adherence optimization according to guidelines. Implementation of longer-term medication adherence interventions in the daily clinic may contribute to the improvement of progression-free survival. ClinicalTrials.gov NCT04484064.

How Patient-Centered is Education and Counseling of Patients on Oral Anticancer Therapy? A Multicenter Cross-sectional study

Background: In the last years, there has been an exponential increase in the number of oral anticancer therapies (OACT). However, no research has yet been conducted on the current quality of patient-centered care (PCC) for patients on OACT in Belgium. Moreover, there was no valid and reliable instrument available to assess PCC tailored to the context of OACT. Therefore, we developed and validated a new patient-reported experience measure (PREM), named the CONTACT-Patient-Centered Care Questionnaire (CONTACT-PCCQ).
 Aim: The aim of this study was to gain insight in the quality of PCC for patients on OACT using the CONTACT-PCCQ. It was examined which areas of patient-centered education and counseling are currently being performed adequately, according to patients, and which areas require improvement.
 Methods: This was a multicenter cross-sectional study. Patients were recruited in 11 hospitals in Belgium. They completed the CONTACT-PCCQ online or on paper. The CONTACT-PCCQ consists of 86 items, which all represent a key element (KE) in patient-centered education and counseling for patients on OACT. The items are divided into seven subscales: A1) medication counselling at the start of OACT, A2) follow-up of OACT, B) communication style, C) counseling by hospital treatment team, D) counseling by primary care healthcare professionals, E) psychosocial support, and F) involvement of family and friends. Patients were asked to indicate how they experienced the performance of each KE on a 5-point Likert rating scale. The answer options were dichotomized into ‘performed’ and ‘not performed’. Subsequently, the degree of performance of each item was defined by calculating the proportion of patients that indicated that the item was performed. On subscale-level, mean total scores were calculated.
 Findings: In total, 266 patients completed the CONTACT-PCCQ. Subscale C ‘Commitment and cooperation between healthcare professionals’, concerning care coordination in the hospital, had the highest mean subscale score. The lowest score was obtained on subscale D ‘Involvement of primary care’. The degree of performance of all items ranged from 22% to 95%. Items regarding specific topics in patient education (e.g., what do to in case of vomiting, which food to avoid during treatment) and adherence monitoring scored low. Low scores were also obtained on the items about the involvement of the community pharmacist and homecare nurse - in contrast to the items regarding the general practitioner. Some other items, e.g., regarding information about vaccinations and palliative care, were also scored low by patients. In general, KEs on communication style (e.g. HCPs left enough opportunity to ask questions, HCPs took sufficient time for a proper conversation) received high scores.
 Discussion and conclusion: This study gave insight in the overall quality of patient-centered education and counselling for patients on OACT. Three gaps in PCC were uncovered: unmet patient information needs due to shortcomings in patient education, inadequate adherence monitoring, and lacking collaboration with community pharmacists and home care nurses. These results enable hospitals and policy makers to set priorities in care quality improvement for patients on OACT.

Building Quality Improvement Initiatives through Anti-Cancer Stewardship in the Veterans Health Administration (VHA): CML Pilot

The Department of Veterans Affairs (VA) Pharmacy Benefits Management (PBM) Services created a national stewardship with focus on anti-cancer therapeutics within a disease-specific cohort . Directing stewardship initiatives to a cohort of Veterans with a common malignancy is a novel approach. A multidisciplinary team with National PBM and VISNs (Veterans Integrated Service Network) promotes standardization of practice with accountability to monitor outcomes as a continual quality improvement process. A toolkit was built to support stewardship activities and includes: near-real-time process to identify a national disease-specific Veteran cohortdisease validation processcentralized MUE data collectioneducational resourcessite for communication and training materials Tyrosine Kinase Inhibitors (TKIs) account for the second highest utilization among outpatient oral anti-cancer therapies in VHA . Imatinib has demonstrated persistent efficacy and is the preferred TKI on the VA National Formulary. Utilizing our toolkit, we developed two MUEs for our national CML cohort to determine why Veterans were not prescribed imatinib as 1L therapy and reasons for switching from first to second line therapy. Methods Business rules identified VISN CML cohorts by using data sources and diagnostic coding from the VA Electronic Health Record (EHR): primary care and hematology/oncology visits (ICD-10), inpatient stays (ICD-10), and problem lists (ICD-10; SNOMED CT). Retrospective chart review of two subsets: Veterans who received a drug other than imatinib as their initial VA prescriptionVeterans who received at least two unique drugs to treat CML Data abstracted for MUE #1: Disposition of TKI prescriptionIf new initiation, documented reason(s) for drug selectionIf continuation, prior drug therapy history Data abstracted for MUE #2: Documented reason(s) for switch to 2LIf adverse drug reaction (ADR) included as a reason, is it documented in the EHR? Analysis combined responses with prescription data from the EHR. Results Of the 18 VISNs, 9 participated in MUE data collection. 365 patients were identified as not having received imatinib 1L and 360 were identified as having received at least two unique drugs to treat CML. These counts are each approximately 30% of the total CML patient cohort. In the total cohort, ~50% of patients received imatinib 1L and have not switched to 2L. Responses for 1L TKI therapy (N=365) 199 (55%) continued therapy originally started outside VA with 67% of these patients (n=133) without documentation of prior imatinib therapy166 (45%) were newly initiating CML therapy with top documented reasons for drug selection: Intermediate or high risk (e.g., SOKAL risk scoring): 77 (46%)46 (28%)18 (11%)Dasatinib was the most prescribed 1L therapy in this cohort (64%; 235), followed by nilotinib (23%; 85), which had a higher prevalence when therapy was continuation (30%).53 patients (15%) had subsequent imatinib therapyResponses for switch from 1L to 2L therapy (N=360) Top documented reasons for switch from 1L to 2L therapy 215 (60%)81 (23%)Resistance / inadequate response: 69 (19%)Only 37 (17%) who experienced an ADR had it documented in the EHRThe most common 2L drug was dasatinib (55%;198). The median number of days between 1L and 2L initiation was 275 (range: 7 - 2, 573)136 patients (38%) received third line therapy or beyond Conclusions A formalized oncology stewardship with focus on disease-specific initiatives within a national healthcare system is feasible. Responses from our 1L MUE indicate that despite geography, imatinib remains the preferred TKI and accounts for the highest utilization. Most veterans not receiving imatinib as 1L therapy, received dasatinib or nilotinib. Continuation of therapy due to transition of care to VA was the primary reason for 1L therapy with a non-preferred TKI. Other reasons included: FDA indication and SOKAL risk scoring. In our pilot 1L to 2L MUE, ADRs were the most common reason for CML patients to be switched to 2L (45%) followed by resistance/inadequate response and disease progression . Most ADRs were not documented in the EHR. Further interventions in TKI prescribing may be instituted in select sites . Following initiatives for CML, Anti-Cancer Stewardship will be expanded to other oncologic diseases.

Sweet Cherry Extract as Permeation Enhancer of Tyrosine Kinase Inhibitors: A Promising Prospective for Future Oral Anticancer Therapies.

Although patients would rather oral therapies to injections, the gastrointestinal tract's low permeability makes this method limiting for most compounds, including anticancer drugs. Due to their low bioavailability, oral antitumor therapies suffer from significant variability in pharmacokinetics and efficacy. The improvement of their pharmacokinetic profiles can be achieved by a new approach: the use of natural extracts enriched with polyphenolic compounds that act as intestinal permeability enhancers. Here, we propose a safe sweet cherry extract capable of enhancing oral absorption. The extract was characterized by the HPLC-UV/MS method, evaluated for in vitro antioxidant activity, safety on the Caco-2 cell line, and as a potential permeation enhancer. The sweet cherry extract showed a high antioxidant capacity (ABTS and DPPH assays were 211.74 and 48.65 µmol of Trolox equivalent/g dried extract, respectively), high content of polyphenols (8.44 mg of gallic acid per gram of dry extract), and anthocyanins (1.80 mg of cyanidin-3-glucoside equivalent per g of dry extract), reassuring safety profile (cell viability never lower than 98%), and a significant and fully reversible ability to alter the integrity of the Caco-2 monolayer (+81.5% of Lucifer yellow permeability after 2 h). Furthermore, the ability of the sweet cherry extract to improve the permeability (Papp) and modify the efflux ratio (ER) of reference compounds (atenolol, propranolol, and dasatinib) and selected pyrazolo[3,4-d]pyrimidine derivatives was investigated. The obtained results show a significant increase in apparent permeability across the Caco-2 monolayer (tripled and quadrupled in most cases), and an interesting decrease in efflux ratio when compounds were co-incubated with sweet cherry extract.

CN42 A pharmacist-led interprofessional medication adherence program improved adherence to oral anticancer therapies: The OpTAT randomized controlled trial

CN42 A pharmacist-led interprofessional medication adherence program improved adherence to oral anticancer therapies: The OpTAT randomized controlled trial

Sponsor Perspectives on the Impact of the COVID-19 Pandemic on Interventional Cancer Clinical Trial Protocols and Data Quality.

The onset of the COVID-19 pandemic created major disruptions in the conduct of cancer clinical trials. In response, regulators and sponsors allowed modifications to traditional trial processes to enable clinical research and care to continue. We systematically evaluated how these mitigation strategies affected data quality and overall trial conduct. This study used surveys and live interviews. Forty-one major industry and National Cancer Institute Network groups (sponsors) overseeing anticancer treatment trials open in the United States from January 2015 to May 2022 were invited to participate. Descriptive statistics were used for survey data summaries. Key themes from interviews were identified. Twenty sponsors (48.8%; 15 industry and five Network groups) completed the survey; 11/20 (55.0%) participated in interviews. Sponsors predominantly (n = 12; 60.0%) reported large (≥11 trials) portfolios of phase II and/or phase III trials. The proportion of sponsors reporting a moderate (9) or substantial (8) increase in protocol deviations in the initial pandemic wave versus the pre-pandemic period was 89.5% (17/19); the proportion reporting a substantial increased dropped from 42.1% (n = 8/19) in the initial wave to 15.8% (n = 3/19) thereafter. The most commonly adopted mitigation strategies were remote distribution of oral anticancer therapies (70.0%), remote adverse event monitoring (65.0%), and remote consenting (65.0%). Most respondents (15/18; 83.3%) reported that the pandemic had minimal (n = 14) or no impact (n = 1) on overall data integrity. Despite nearly all sponsors observing a temporary increase in protocol deviations, most reported the pandemic had minimal/no impact on overall data integrity. The COVID-19 pandemic accelerated an emerging trend toward greater flexibility in trial conduct, with potential benefits of reduced burden on trial participants and sites and improved patient access to research.

Impact of COVID-19 pandemic mitigation strategies on industry and NCI cancer treatment trials.

1565 Background: The onset of the COVID-19 pandemic resulted in major disruptions in enrollment and conduct of cancer clinical trials. In response, regulators allowed modifications to traditional trial processes to enable clinical research and care to continue. The American Society of Clinical Oncology and Friends of Cancer Research established a task force to evaluate how sponsors perceived the impact of these mitigation strategies on data quality and overall trial conduct. Methods: The study used a survey and live interviews of industry and National Cancer Institute (NCI) cooperative group sponsors of cancer treatment trials. Sponsors with trials active in the United States from January 2015-May 2022 were eligible. We assessed perceived impacts of the pandemic on protocol deviations, types of mitigation strategies, trial closures, dropouts, adverse events (AEs), and data integrity. Descriptive statistics were used for survey data summaries. Key findings from semi-structured interviews were described by theme. Results: Of forty-one eligible sponsors, 20 (49%; 15/36 industry and 5/5 cooperative group) completed the survey; eleven (55%; 7/15 industry and 4/5 cooperative group) were interviewed. Sixty percent of sponsors reported large portfolios (>10 trials) of phase II and/or phase III trials. The most widely adopted mitigation strategies were remote distribution of oral anticancer therapies (70%), remote consenting (65%), and remote symptom monitoring for AEs (65%). The proportion of sponsors reporting a “substantial” increase in protocol deviations compared to the pre-pandemic period dropped from 42% in the initial wave (March-April 2020) to 16% thereafter. Sponsors primarily reported “no change” in trial drop-out rates (77%), the number of trials closed due to low accrual (90%), or rates of AEs (81%) at any point during the pandemic. Overall, most (83%) respondents reported the pandemic had “minimal” (14) or “no” impact (1) on data integrity. In interviews, many sponsors reported persistent time delays in data entry related to labor shortages at sites. Conclusions: This study represents the first systematic evaluation of clinical trial sponsors about the impact of the COVID-19 pandemic on the conduct of cancer clinical trials. Remote clinical trial conduct mitigation strategies were broadly adopted. Despite an observed increase in protocol deviations, most sponsors reported the pandemic had minimal or no impact on data integrity. The COVID-19 pandemic impacted how cancer clinical trials were performed and has likely accelerated a trend towards greater flexibility in trial conduct that was already emerging, with potential benefits of reduced burden and improved access for patients and sites . Future work is planned to further quantify the impact of the pandemic and trial mitigation strategies on the quality of trial data both overall and for historically underrepresented patient groups.

The cocreation of care pathways for patients treated with oral anticancer drugs: From assessment data to an actual care pathway.

Due to the emergence of oral anticancer therapies, existing care processes in oncology - that are mainly focused on in-hospital treatments - must be rethought. The development of a care pathway is a well-known methodology to reorganise and standardise care for a specific patient group. However, care pathway development might be complex and burdensome for healthcare teams, requiring a well-thought-out methodology that provides guidance to the teams. In 10 Belgian oncology departments, multidisciplinary teams developed a tailored care pathway, aimed to offer high-quality patient-centred care. Each department followed a cocreation methodology, consisting of a current practice assessment, a priority setting, and the actual development of the care pathway. The aim of this study was to investigate how and to which extent underperformed evidence-based key elements (KEs), identified in the current practice assessment, guided the development of the care pathway, and how compliant the final care pathways are with the list of evidence-based KEs. A qualitative content analysis was conducted to describe and compare the results of each phase of the cocreation methodology. This study shows that much of the evidence and feedback on current practice that was used as a starting point, got lost throughout the cocreation process. Only a limited proportion of the (seriously) underperformed KEs were prioritised by the multidisciplinary teams. Furthermore, several prioritised KEs could not be retrieved in the care pathway documents. Also, the final care pathways were not fully compliant with existing evidence. Based on the findings, a more rigorous cocreation methodology seems needed, offering very concrete support for multidisciplinary teams to integrate the prioritised KEs in the care process (e.g., by using a model care pathway). Next to the selfreported performance data from healthcare professionals and patients, more objective data (e.g., walkthrough, medical records) and more extensive patient involvement should be considered in the priority setting.

Adherence With Oral Anticancer Therapies: Clinical Trial versus Real-World Experiences with a Focus on Prostate Cancer.

In this review, we address adherence rates in clinical settings, barriers to compliance with dosing schedules, and potential strategies to overcome challenges in maintaining high levels of adherence. Four studies reporting real-world adherence to prostate cancer medications, 52 studies describing barriers to adherence, and 16 studies on methods to minimize poor adherence were reviewed. Mean nonadherence rates of 25 to 51% have been identified in prostate cancer patients prescribed oral therapies, with higher rates in older patients. An extensive review of prostate cancer patients receiving gonadotropin hormone-releasing hormone agonist injections found an overall nonadherence rate of over 27%. Patients may encounter barriers to complying with dosing instructions related to the medication (eg, complex dosing schedules, the total burden of medication management, fasting or dietary requirements, high medication costs, adverse effects, and drug-drug interactions). Barriers may also be related to patient-specific factors (eg, suboptimal education regarding the importance of adherence, physical limitations and cognitive decline associated with advancing age, living alone without a care partner, high symptom burden, needle phobia, and comorbid mental disorders). Interventions to improve dosing adherence may include automated reminders, treatment diaries, educational materials, and the involvement of patients, family members, care partners, and healthcare teams. Many oral anticancer medications improve survival in men with prostate cancer and therefore it is vital to establish good adherence by understanding the pitfalls that patients may encounter. In situations where both oral and injectable drugs are interchangeable, injections of long-acting drugs lead to fewer opportunities for dosing nonadherence than oral therapies. In contrast, oral medicines do not require scheduling for injections and travel for injection appointments. Therefore, maximizing adherence to all treatment regimens will reduce the chance of efficacy failures and likely lead to improved clinical outcomes.

278MO Adherence optimisation, benefits, and limitations of oral anti-cancer therapy: A systematic review of patient preferences

Oral anti-cancer (OAC) therapies are now commonplace in cancer treatment. Variable adherence and irregular toxicity monitoring remain concerning, particularly for treatments with curative intent. This study reviews literature on patient preferences considering: 1) factors contributing to patient adherence; 2) benefits and limitations; 3) concordance between patient and clinician perspectives.

Trends in Medicare oral anticancer drug utilization among relapsed and refractory chronic myeloid leukemia patients.

e19058 Background: The treatment landscape for patients with relapsed and refractory (RR) chronic myeloid leukemia (CML) has changed significantly in recent years, with the introduction of targeted oral anticancer therapies. Current guidelines from the National Cancer Comprehensive Network (NCCN) recommend tyrosine-kinase inhibitors (TKIs) for second line and subsequent therapy. Recent real-world data evaluating treatment patterns in RR CML is limited. Study objective was to evaluate treatment patterns and trends in utilization of oral anticancer agents among Medicare beneficiaries diagnosed with RR CML, from 2017-2019. Methods: Retrospective study using Medicare Part D Prescription Drug Event Files, which contain records on prescription drug fills among Medicare beneficiaries enrolled in Fee-for-Service and Medicare Advantage plans. Beneficiaries diagnosed with RR CML (C9212 ICD-10) and prescribed oral anti-cancer therapy (Bosutinib, Dasatanib, Nilotinib, Ponatinib or Imatinib Mesylate) were identified and followed for at least 12 months, from index diagnosis until end of study period (December 31, 2019) or death. Trends in utilization by oral therapy, by number of beneficiary utilizers and prescription drug claims, were evaluated from 2017 to 2019. Results: Overall, 327 Medicare beneficiaries with a diagnosis of RR MM were prescribed an oral TKI therapy (Bosutinib, Dasatanib, Nilotinib, Ponatinib or Imatinib Mesylate) throughout the study period (2017-2019). The number of beneficiaries prescribed at least 1 oral therapy increased between 2017 and 2019, from 154 to 212 (Table). Total utilization also increased: from 210 prescription drug claims in 2017 to 296 in 2019. Throughout the study period, Imatinib Mesylate had the largest market share among all oral therapies, however the share decreased over time (from 35.7% in 2017 to 30.7% in 2019). Nilotinib had the largest gain in market share during this period, from 15.7% to 20.9%. Conclusions: Study findings suggest utilization of oral therapies are increasing over time, and shifting from Imatinib Mesylate to newer therapeutic agents. Given the high costs for these novel therapies, future research should examine trends in patient out-of-pocket spending, as well as factors impacting patient adherence.[Table: see text]

Adherence to oral anti-cancer therapies in older patients is similar to that of younger patients.

The use of oral anti-cancer therapies is becoming increasingly common in the management of cancers, raising the question of adherence. The objective of this study was to assess adherence to oral anti-cancer therapies, as well as the impact of various factors that may influence it. Patients starting oral chemotherapy (tyrosine kinase inhibitor or cytotoxic) were followed up for 3 months using a medication diary, which was given to the patient by the pharmacist during a multidisciplinary consultation. Adherence was assessed using the diary, as well as by counting the tablets they brought back. One hundred and fifty patients were included in the study. The main oral chemotherapy agents prescribed were palbociclib (23.3%), everolimus (18.7%), and capecitabine (13.3%). The adherence at the end of the 3 months, by means of dose intensity (i.e. percent of the dose prescribed that has been taken), was 95.5%. No significant difference in adherence was found based on age, sex, family circumstances, health status, co-medication, type of oral therapy, tumor location, number of previous treatment lines, or presence of toxicity. The main reasons for non-adherence were forgetting (50%) and toxicity (21%). Fifty-seven patients prematurely discontinued the study: 40.3% for toxicity and 36.8% for disease progression. Adherence in this study is high in comparison to literature, which can be explained by close multidisciplinary follow-up. Moreover, no significant difference was observed between younger and older patients.

Drug-Drug Interactions With Over-The-Counter Medicines: Mind the Unprescribed.

This review provides a summary of the currently available clinical data on drug-drug interactions (DDIs) involving over-the-counter (OTC) medicines. It aims to educate and increase awareness among health care providers and to support decisions in daily practice. An extensive literature search was performed using bibliographic databases available through PubMed.gov. An initial structured search was performed using the keywords "drug-drug-interaction AND (over-the-counter OR OTC)," without further restrictions except for the language. The initial results were screened for all described DDIs involving OTC drugs, and further information was gathered specifically on these drugs using dedicated database searches and references found in the bibliography from the initial hits. From more than 1200 initial hits (1972-June 2021), 408 relevant publications were screened for DDIs involving OTC drugs, leading to 2 major findings: first, certain types of drug regimens are more prone to DDIs or have more serious DDI-related consequences, such as antiretroviral, anti-infective, and oral anticancer therapies. Second, although most DDIs involve OTC drugs as the perpetrators, some prescription drugs (statins or phosphodiesterase-5 inhibitors) that currently have OTC status can be identified as the victims in DDIs. The following groups were identified to be frequently involved in DDIs: nonsteroidal anti-inflammatory drugs, food supplements, antacids, proton-pump inhibitors, H2 antihistamines, laxatives, antidiarrheal drugs, and herbal drugs. The most significant finding was the lack of high-quality evidence for commonly acknowledged interactions. High-quality interaction studies involving different phenotypes in drug metabolism (cytochrome P450) and distribution (transporters) are urgently needed. This should include modern and critical drugs, such as oral anticancer medications and direct oral anticoagulants.

A Remote Monitoring System to Optimize the Home Management of Oral Anticancer Therapies (ONCO-TreC): Prospective Training-Validation Trial.

BackgroundA platform designed to support the home management of oral anticancer treatments and provide a secure web-based patient–health care professional communication modality, ONCO-TreC, was tested in 3 cancer centers in Italy.ObjectiveThe overall aims of the trial are to customize the platform; assess the system’s ability to facilitate the shared management of oral anticancer therapies by patients and health professionals; and evaluate system usability and acceptability by patients, caregivers, and health care professionals.MethodsPatients aged ≥18 years who were candidates for oral anticancer treatment as monotherapy with an Eastern Cooperative Oncology Group performance status score of 0 to 1 and a sufficient level of familiarity with mobile devices were eligible. ONCO-TreC consisted of a mobile app for patients and a web-based dashboard for health care professionals. Adherence to treatment (pill count) and toxicities reported by patients through the app were compared with those reported by physicians in medical records. Usability and acceptability were evaluated using questionnaires.ResultsA total of 40 patients were enrolled, 38 (95%) of whom were evaluable for adherence to treatment. The ability of the system to measure adherence to treatment was high, with a concordance of 97.3% (95% CI 86.1%-99.9%) between the investigator and system pill count. Only 60% (3/5) of grade 3, 54% (13/24) of grade 2, and 19% (7/36) of grade 1 adverse events reported by physicians in the case report forms were also reported in the app directly by patients. In total, 94% (33/35) of patients had ≥1 app launch each week, and the median number of daily accesses per patient was 2. Approximately 71% (27/38) and 68% (26/38) of patients used the app for messages and vital sign entering, respectively, at least once during the study period.ConclusionsONCO-TreC is an important tool for measuring and monitoring adherence to oral anticancer drugs. System usability and acceptability were very high, whereas its reliability in registering toxicity could be improved.Trial RegistrationClinicalTrials.gov NCT02921724; https://www.clinicaltrials.gov/ct2/show/NCT02921724

Addressing the Challenges of Novel Oncology and Hematology Treatments Across Sites of Care: Specialty Pharmacy Solutions.

Background: The number of Food and Drug Administration (FDA) approvals for anticancer therapies has significantly increased in recent years, but these novel therapies are costly and present challenges to patients and providers. Many institutions have implemented health systems specialty pharmacies (HSSPs) to help patients and providers navigate financial and logistical barriers to treatment with oral anticancer therapies. Patients on oral anticancer therapy are often treated across multiple sites of care which can complicate the inpatient specialty medication initiation process. Health systems often limit inclusion of oral anticancer therapies for inpatient administration due to costs, however several new therapies necessitate admission for treatment initiation. Health systems are then faced with the challenge of starting costly oral anticancer therapy inpatient and ensuring continued access to therapy upon discharge. We describe the integrated HSSP multidisciplinary approach to this MUP including providers, inpatient and outpatient pharmacists, specialty and inpatient pharmacies, institutional procurement team, and the institutional pharmacy and therapeutics (P&T) committee to streamline this process.The HSSP multidisciplinary processes addresses a growing need for cancer patients to receive timely and affordable treatments across different sites of care. The healthcare team and P&T committee ensure the patient receives the most appropriate therapy while being conscious of health-system costs. The HSSP and procurement team ensure the patient can obtain and afford the medication. The implemented processes allows for direct communication and collaboration between different sites of care and this collaborative approach leads to optimal patient care.

Interventions to support adherence to oral anticancer therapies: research challenges, lessons learned, and strategies to overcome them from Australia and Switzerland.

Not monitoring adherence to oral anticancer therapies (OAT) can lead to poor clinical outcomes, including premature death as reported by Foulon et al. (Acta Clin Belg 66(2):85-96, 2011) and Greer et al. (Oncologist 21(3):354-76, 2016). Barriers to the implementation of supportive cancer care interventions in medication adherence occur with multiple hospital sites, cancer diagnoses, and numerous healthcare professionals. This commentary describes challenges and strategies from two OAT adherence trials in Australia and Switzerland to assist researchers in the design and implementation of future interprofessional trials.