Oral Anticancer Agent Research Articles

Predictors of self-care in patients with cancer treated with oral anticancer agents: A systematic review.

In the last two decades, the use of oral anticancer agents (OAAs) has increased in cancer patients. Despite this, patients and their caregivers face some challenging issues (side effects, drug-to-drug interactions, etc.) related to OAA administration. The three dimensions of self-care by Riegel et al., self-care maintenance (i.e., stability of patient condition), self-care monitoring (i.e., detection of side effects), and self-care management (i.e., management of side effects), may be implemented to avoid negative outcomes. However, knowledge of self-care determinants is necessary to recognise people at risk of poor self-care behaviours. Determine which are the predictors of self-care maintenance, self-care monitoring and self-care management in patients with cancer taking OAA. A systematic review with narrative synthesis was conducted. We included studies on adult patients with cancer using any kind of oral anticancer agent and describing a predictor of self-care. The search was performed on PubMed, CINAHL/PsycINFO, and Web of Science. Of 3,061 records, 45 studies were included in this review. Forty-six predictors organised into 14 categories were identified. In general, all studies focused only on adherence, considered as a self-care maintenance component, and none of them focused on other dimensions of self-care. The predictors of OAA adherence most reported were age, side effects, and socioeconomic factors (e.g., insurance status, and annual income). This systematic review highlighted the literature gap on the analysis of determinants of self-care behaviours in patients taking OAAs. This element could be a starting point for future research that can provide elements to support the oncology nursing research agenda, aimed at recognising patients at risk of poor self-care.

The relationship between medication beliefs, patient activation, and self-rated health in patients taking oral anticancer agents.

Patients on oral anticancer agent (OAA) therapies have the autonomy to manage their cancer treatments in home settings. However, patients may not have adequate knowledge, confidence, or ability to effectively manage OAA-related consequences, which can significantly impact their treatment and health outcomes. This study aims to identify the associations between medication beliefs, patient activation, and self-rated health (SRH) among oncology patients taking OAAs and explore the potential mediation effects of patient activation on the relationship between medication beliefs and SRH. A secondary data analysis was conducted on cross-sectional data from 114 patients who were diagnosed with breast, colorectal, lung, or prostate cancer. Patients completed a self-reported survey including items of SRH, Beliefs about Medicines Questionnaire (BMQ), and Patient Activation Measure (PAM-13). Descriptive statistics, bivariate correlation, hierarchical multiple linear regression, and mediation analysis were conducted. The results indicate that patients taking OAAs have ambivalent attitudes toward medication. Both medication necessity (r = - 0.27) and concerns (r = - 0.21) were negatively associated with SRH, while patient activation was positively associated with SRH (r = 0.38). Patient activation had a negative association with medication concerns (r = - 0.36) and fully mediated the relationship between medication concerns and SRH in patients taking OAAs (indirect effect = - 0.154, 95% confidence interval, - 0.276 to - 0.060). The findings highlight the significance of activating patients to better understand and manage their OAAs. It is crucial for oncology professionals to provide multifaceted interventions to promote patient activation with an effort to mitigate the negative impact of medication beliefs on patient-perceived health outcomes.

Preclinical antitumor efficacy of ETN101, a novel oral anticancer agent with Wnt/ß-catenin signaling inhibition, TME modulation, and VEGFR2 targeting for advanced hepatocellular carcinoma treatment.

e16138 Background: Hepatocellular carcinoma (HCC) is an important cancer in worldwide with over 900,000 new cases and approximately 830,000 deaths were reported in 2020. It ranks sixth in global cancer incidence and third in mortality, highlighting its worldwide significance. The high frequency of occurrence and elevated mortality rates contribute to a significant socio-economic burden. However, most patients are diagnosed in the middle and late stages, missing the optimal treatment. Therefore, it is necessary to develop novel, safe, and effective drugs for HCC inhibition, elucidating their mechanisms of action. Methods: Evaluation of ETN101 was utilized in subcutaneous xenograft and orthotopic animal models with human HCC cell lines. ETN101 was administered orally. The tumor volume, tumor weight, and bodyweight were measured, and cancer cell proliferation and apoptosis were also analyzed. The toxicity of ETN101 was investigated through GOT/GPT and histological analysis in the liver and kidney. The signaling mechanism of ETN101 was analyzed through kinase analysis, phosphorylation, in silico docking analysis, and RNA sequencing, both in vitro and in vivo. Results: ETN101 demonstrated approximately 30% tumor inhibition at 10 mg/kg group compared to control. Moreover, 20 mg/kg treatment group also showed significant tumor reduction in all individuals with one complete response (CR). Interestingly, all individuals exhibited CR from 40 to 82 mg/kg treatment groups. During the 10 administrations of Nexavar and Lenvatinib, individuals who showed proliferated tumors persistently were selected, followed by the administration of ETN101. All individuals exhibited either CR or significant reduction in tumor volume upon ETN101. After tracking complete responders for two months, there were no signs of tumor recurrence or metastasis. These results suggested that ETN101 has anticancer effect by regulating Wnt/ß-catenin pathway in tumor microenvironment (TME) with increasing the infiltration of cytotoxic T cells into the tumor. Furthermore, it targets VEGFR2, blocking angiogenesis-related signals to improve therapeutic effects in advanced HCC. Conclusions: Due to lack of effective single drugs for advanced HCC patients, combination therapy is used clinically. We developed ETN101, a monotherapy that targets VEGFR2 and modulates the TME with the same mechanism as the combination therapy. ETN101 also showed excellent efficacy in preclinical study and secured a broad safety margin relative to the effective dose. In addition, ETN101 was effective in those who are not responded to conventional targeted cancer therapies. It is anticipated that ETN101 could serve as a novel therapeutic strategy for advanced HCC patients.

Area Vulnerability and Disparities in Therapy for Patients With Metastatic Renal Cell Carcinoma.

Area-level measures of sociodemographic disadvantage may be associated with racial and ethnic disparities with respect to receipt of treatment for metastatic renal cell carcinoma (mRCC) but have not been investigated previously, to our knowledge. To assess the association between area-level measures of social vulnerability and racial and ethnic disparities in the treatment of US Medicare beneficiaries with mRCC from 2015 through 2019. This retrospective cohort study included Medicare beneficiaries older than 65 years who were diagnosed with mRCC from January 2015 through December 2019 and were enrolled in fee-for-service Medicare Parts A, B, and D from 1 year before through 1 year after presumed diagnosis or until death. Data were analyzed from November 22, 2022, through January 26, 2024. Five different county-level measures of disadvantage and 4 zip code-level measures of vulnerability or deprivation and segregation were used to dichotomize whether an individual resided in the most vulnerable quartile according to each metric. Patient-level factors included age, race and ethnicity, sex, diagnosis year, comorbidities, frailty, Medicare and Medicaid dual enrollment eligibility, and Medicare Part D low-income subsidy (LIS). The main outcomes were receipt and type of systemic therapy (oral anticancer agent or immunotherapy from 2 months before to 1 year after diagnosis of mRCC) as a function of patient and area-level characteristics. Multivariable regression analyses were used to adjust for patient factors, and odds ratios (ORs) from logistic regression and relative risk ratios (RRRs) from multinomial logistic regression are reported. The sample included 15 407 patients (mean [SD] age, 75.6 [6.8] years), of whom 9360 (60.8%) were men; 6931 (45.0%), older than 75 years; 93 (0.6%), American Indian or Alaska Native; 257 (1.7%), Asian or Pacific Islander; 757 (4.9%), Hispanic; 1017 (6.6%), non-Hispanic Black; 12 966 (84.2%), non-Hispanic White; 121 (0.8%), other; and 196 (1.3%), unknown. Overall, 8317 patients (54.0%) received some type of systemic therapy. After adjusting for individual factors, no county or zip code-level measures of social vulnerability, deprivation, or segregation were associated with disparities in treatment. In contrast, patient-level factors, including female sex (OR, 0.78; 95% CI, 0.73-0.84) and LIS (OR, 0.48; 95% CI, 0.36-0.65), were associated with lack of treatment, with particularly limited access to immunotherapy for patients with LIS (RRR, 0.25; 95% CI, 0.14-0.43). Associations between individual-level factors and treatment in multivariable analysis were not mediated by the addition of area-level metrics. Disparities by race and ethnicity were consistently and only observed within the most vulnerable areas, as indicated by the top quartile of each vulnerability deprivation index. In this cohort study of older Medicare patients diagnosed with mRCC, individual-level demographics, including race and ethnicity, sex, and income, were associated with receipt of systemic therapy, whereas area-level measures were not. However, individual-level racial and ethnic disparities were largely limited to socially vulnerable areas, suggesting that efforts to improve racial and ethnic disparities may be most effective when targeted to socially vulnerable areas.

Identifying metrics and designing measurable outcomes in the electronic health record to evaluate pharmacist intervention in an oral chemotherapy program.

Due to the increased utilization of oral anticancer agents, pharmacist-led oral anticancer programs have emerged to meet the needs of oral anticancer management. Currently, at Froedtert & MCW, there is a lack of established tools to collect metrics which demonstrate the value of a pharmacist-led oral anticancer program. The purpose of this project is to establish metrics that reflect the interventions pharmacists are performing, and second, to develop a documentation tool which can reliably extract discrete data on the identified metrics. Eight of the 10 desired metrics were included in the documentation tool. Two questionnaires were created to allow for easy data retrieval of the metrics. The "initial" questionnaire focuses on interventions made at the time of starting an oral anticancer agent, while the "follow-up" questionnaire focuses on interventions made during the subsequent monitoring. The introduction of the questionnaire tool was well received by end users and did not add to the pharmacist's overall workload. By establishing metrics that reflect pharmacist interventions in a pharmacist-led oral anticancer program and creating a documentation tool to collect discrete data related to those metrics from the electronic health record, we at Froedtert & MCW are better able describe the workload of the ambulatory oncology pharmacists with regard to their interventions and monitoring of oral anticancer agents. This data will be used to establish differences in pharmacist workload between clinics, justify pharmacist resources, and provide a snapshot of the patient population served as part of the oral anticancer program.

Patient symptoms, self-management, and unscheduled healthcare use during the first 6 months of targeted oral anticancer agent therapy: protocol for a mixed-methods US study

IntroductionTargeted oral anticancer agents (OAAs) are increasingly used to treat cancer, including haematological malignancies and ovarian cancer, but they can cause serious symptomatic side effects such as arrhythmias, hypertension, and...

Analysis of tumor biomarkers in patients (pts) with advanced hepatocellular carcinoma (HCC) from a phase 1b study of E7386, a CREB-binding protein/β-catenin interaction inhibitor, in combination with lenvatinib.

535 Background: E7386, a novel oral anticancer agent, inhibits β-catenin binding to its transcriptional co-activator CREB-binding protein, thus modulating Wnt/β-catenin signaling. Lenvatinib is a multikinase inhibitor that targets VEGFR 1–3, FGFR 1–4, PDGFRα, RET, and KIT. We previously reported the safety/tolerability, pharmacokinetics, biomarkers, and preliminary efficacy of E7386 plus lenvatinib in 25 pts with HCC in the dose escalation part of a phase 1b study1 (NCT04008797). Here, we present the results of exploratory tumor biomarker analyses from this study. Methods: Pts with HCC were treated with E7386 10–80 mg QD and 60–120 mg BID plus lenvatinib (bodyweight < 60 kg: 8 mg QD; ≥ 60 kg: 12 mg QD). Archival or fresh tumor samples were collected at baseline and post-treatment; tumor tissue was assessed for genetic alteration, immunohistochemistry (IHC), and gene expression. Gene signature scores of interest were calculated using obtained gene expression data. The preliminary association between biomarker status and efficacy was investigated. Results: Of the 25 pts enrolled, 22 had baseline tumor samples available for the gene mutation analysis. TERT (6 pts: 27%), CTNNB1 (5 pts: 23%), and TP53 (4 pts: 18%) mutations were detected. CTNNB1 mutation was confirmed in 3 of 7 responders and 2 of 13 non-responders. Nuclear β-catenin expression was confirmed by IHC analysis in 5 of 16 pts; it was expressed in 3 of 5 pts with CTNNB1 MUT and 2 of 11 pts with CTNNB1 WT. Pts with expression of nuclear β-catenin had 2 partial responses (PRs) among 5 pts; those without β-catenin expression had 2 PRs among 11 pts. Additionally, IHC analysis of tumor microvessel density (MVD; number of CD31+ vessels) at baseline suggested that greater maximum tumor shrinkage (MTS) tended to be observed in the MVD-high population compared to the MVD-low population. 7 Pts had evaluable baseline and post-baseline tumor samples and were included in the gene signature analysis. Despite the small sample size, preliminary results indicated that MTS may be associated with a decrease in Wnt signaling and angiogenesis gene signature scores (spearman r [r]=0.61 for both) and attenuation of hypoxic induction and glycolysis gene signature scores (r=0.79 and 0.68, respectively). Conclusions: These exploratory tumor biomarker analyses suggest that E7386 in combination with lenvatinib may affect the tumor microenvironment in HCC pts through effects on Wnt signaling, angiogenesis, hypoxic response, and glycolysis pathways. This concept is the basis for treatment with this combination. However, given the small sample size, further investigation is needed to confirm these effects on the tumor microenvironment. Enrollment of pts with HCC to the expansion part of Study 102 is ongoing. 1. Ikeda et al. ASCO 2023. Clinical trial information: NCT04008797 .

Video reflexive ethnography as an intervention to improve oral anti-cancer agent patient education: A pilot study.

Oral anticancer agents (OAAs) are associated with side effects that interfere with medication adherence, despite patient education regarding side effect management. Video reflexive ethnography (VRE) captures care processes on video that allow participants to learn from videos. The purpose of this pilot study was to assess the usefulness and impact of VRE on improving OAA education. This qualitative study was conducted in a pharmacist-managed OAA clinic: two pharmacists and four patients participated. We filmed each pharmacist providing education to two patients. We conducted patient interviews and one reflexivity session with both pharmacists to learn participants' perspectives. We used thematic content analysis to analyze data. Two themes emerged: what patients liked/helped, and things that were unclear. Patients liked instructions on temperature taking, directions to safely handle and store OAAs. Unclear areas included knowing the timing of the worst side effects.During the reflexivity session, pharmacists found patients' comments useful to improve their practice. VRE was acceptable to pharmacists and patients. Pharmacists recognized VRE as a helpful technique to improve patient education on OAAs. The use of video enables participants to scrutinize and reshape their practices, making VRE a powerful innovation and adjunct to quality improvement initiatives.

Nanoemulsion-Based Orodispersible Film Formulation of Guava Leaf Oil for Inhibition of Oral Cancer Cells.

Among natural sources, guava leaf oil (GLO) has emerged as a potential anticancer agent. However, its limited water solubility poses a significant challenge for its use. Oil-in-water nanoemulsions are used to address the limitation of water solubility of GLO prior to its incorporation into orodipersible films. Nanoemulsions containing GLO:virgin coconut oil (VCO) at a ratio of 50:50 to 70:30 presented a small droplet size of approximately 50 nm and a relatively low zeta potential. GLO:VCO at a ratio of 70:30 was selected for incorporation into sodium alginate film at various concentrations ranging from 1% to 30% w/w. Tensile strength and elongation at break relied on the concentration of nanoemulsions as well as the internal structure of films. Fourier transform infrared spectroscopy revealed that GLO was compatible with sodium alginate. Film containing 2% w/w of nanoemulsions (2G_ODF) exhibited effective in vitro antioral cancer activity, with an IC50 of 62.49 ± 6.22 mg/mL; furthermore, its anticancer activity showed no significant difference after storage at 25 °C for 1 year. Moreover, 2G_ODF at IC60 arrested colony formation and cell invasion. There is also evidence that cell death occurred via apoptosis, as indicated by nuclear fragmentation and positive Annexin-V staining. These findings highlight the potential of orodispersible films containing GLO nanoemulsions as a prospective oral anticancer agent.

Assessing the Feasibility, Acceptability, and Appropriateness of Implementation Strategies Developed to Support an Enhanced Oral Anticancer Agent Adherence Intervention in Academic, Rural Community, and Urban Community Cancer Settings

Background : Oral anticancer agents (OAAs) have changed oncologic treatment and improved patient outcomes in clinical trials (adherence ≥90%), but due to lack of monitoring, side effects, cost, and forgetfulness, benefits have not translated into practice where adherence rates are~ 40%. Our team designed an effective adherence intervention and worked with a stakeholder panel to develop implementation strategies. Overall, we developed 6 distinct strategies for adoption (data driven presentation for program leaders and formal agreement materials), implementation (motivational interviewing (MI) provider course and standard operating procedure (SOP)), and maintenance (key performance indicators (KPIs) and electronic health record (EHR)-integrated adherence assessment) using focus group discussions with clinicians and administrators. Here we use clinician surveys to assess feasibility, acceptability, and appropriateness of strategies. Methods : We administered surveysto establish feasibility, acceptability, and appropriateness of implementation strategies of a medication adherence intervention for OAAs. We adapted surveys using Weiner et. al.'s 2017 psychometric assessment of newly developed implementation outcomes that assigns 15 domains amongst constructs of feasibility, acceptability, and appropriateness to evaluate implementation effort success. The assessment was adapted to make it relevant to the OAA intervention. Participants were queried about feasibility (if it was possible, implementable, doable, easy), appropriateness (if it was a good match, good fit, applicable, suitable), or acceptability (if it was welcome, liked, showed acceptability). Participants rated agreement that implementation strategies exhibited domain characteristics using 5-point Likert scale- 1 (strongly disagree) to 5(strongly agree). Participants also answered open-ended questions by indicating their favorite aspects and suggested recommendations for each strategy. We pilot tested the survey with an advisory panel and edited it using feedback received prior to administration. We performed descriptive statistics for all findings. Results : We administered a survey to hematology and oncology clinicians (n=33) in academic medical centers (n=23), rural community-based centers (n=2), and urban community-based centers (n=7), (no response, n=1). Survey response rate was 31.4%. There were high rates of agreement on the feasibility of SOPs, data driven presentation, and EHR-integrated assessments with 89%, 82%, and 95% of participants indicating a score of ≥4 on a 5-point Likert scale, respectively. There were a moderate rates of agreement on feasibility of KPIs (75%), formal agreement materials (66%), and MI course (50%). There were high rates of agreement on the appropriateness of SOPs, data driven presentations, EHR-integrated assessments, and KPIs with 89%, 93%, 93%, and 82% of participants indicating a score of ≥4 on a 5-point Likert scale, respectively. There were moderate rates of agreement for the MI course (77%) and formal agreement materials (66%). There were high rates of acceptability on data driven presentations, EHR-integrated assessments, KPIs (94-98%), and moderate rates of acceptability on SOPs, formal agreement materials and MIs (67% for all items) as indicated by a score of ≥4 on a 5-point Likert scale. Strategy components that showed a high rate of agreement from participants for inclusion are summarized in Table 1. Participants' favorite part of the presentation was benefit explanation, but they wanted brevity. They appreciated formal agreement for strategic accountability but feared negative consequences. SOPs provides clear roles and helpful diagrams but no flexibility. Participants felt KPIs identify financial impact, but ED visits should be excluded. MI was found effective, but without the hands-on training component. Smart forms were needed for discrete data but difficult to operate. Conclusions :There were moderate to high levels of agreement on most strategies designed to mitigate barriers to implementation of an OAA intervention. Formal agreement materials and motivational interviewing course were shown to be less appropriate and feasible than other strategies. Efforts must be focused on maintaining brevity, highlighting benefit, and clearly defining clinician roles.

Creation and evaluation of oral anticancer agent (OAA) management resources for a thematic quality improvement program.

380 Background: The Hematology/Oncology Pharmacy Association (HOPA) supported a 6-month American Society of Clinical Oncology (ASCO) Quality Training Program (QTP) for its members focused on oral anticancer agent (OAA) management. HOPA’s Oral Chemotherapy Collaborative (OCC) developed 3 resources for use – an OAA program/practice self-assessment, OAA self-reported adherence guide, and OAA dashboard reporting guide. The purpose of this study is to describe resource development and feedback provided by participants. Methods: Three resources were developed by HOPA OCC. The OAA program/practice self-assessment was created based on Michigan Oncology Quality Consortium (MOQC’s) pre-existing OAA self-assessment with the goal of helping practices assess gaps in care and focus area during quality improvement (QI). The OAA adherence guide focused on the clinic-based patient-facing assessment of OAA adherence that identified three recommended adherence surveys and guidance based on responses. Finally, the OAA dashboard guide was created to help sites track their workload and quality-based metrics and included 2 sections – Administrative and Outcome/Quality Metrics. Resources were provided to teams during the 6-month program and feedback related to their usefulness was requested following programming in June 2023. Results: The sample includes 9 respondents from 7 of 9 participating sites. The majority of respondents found the self-assessment to be useful and would recommend its use (Table). Participants ranked the 1-item adherence question as their top preference for self-reported adherence. Of the dashboard administrative metrics, OAA volume, prescription capture rate, and visits were most selected as useful. For the dashboard outcome/quality metrics, number of interventions, patient reported outcomes, time from OAA prescribed to dispense date, prescribed date to start date, prescribed date to 1st follow-up, percent patients receiving education, percent patients with follow-up within defined time period, and percent patients with OAA adherence assessed were most useful. Resources, priority, information technology, and time were most selected as barriers to implementation of the resources. 100% of survey respondents indicated they were likely to recommend participating in the HOPA-ASCO QTP programming. Conclusions: Overall, the thematic programming with resources from HOPA’s OCC was useful. Multiple barriers exist to incorporate best practice aspects of OAA program implementation.[Table: see text]

Multisite results from a practice-based self-assessment for oral anticancer agent (OAA) management.

434 Background: The Hematology/Oncology Pharmacy Association (HOPA) supported a 6-month American Society of Clinical Oncology (ASCO) Quality Training Program (QTP) focused on oral anticancer agent (OAA) management. HOPA’s Oral Chemotherapy Collaborative, developed an OAA self-assessment tool to aid in identifying gaps in care regarding OAAs. The purpose of this study is to describe the results of the OAA baseline self-assessment completed by the participating teams. These results will provide insight into areas of future focus for OAA-based quality improvement. Methods: This multisite, retrospective analysis was conducted in September 2022, prior to the HOPA-ASCO QTP program launch. The OAA Self-Assessment was created by HOPA’s Oral Chemotherapy Collaborative utilizing Michigan Oncology Quality Consortium (MOQC’s) pre-existing OAA self-assessment as a guide. The final self-assessment included standards from MOQC, HOPA, and ASCO/ONS and took approximately 10 minutes to complete. Questions were categorized in the following 6 sections: Prescribing (n=25), Education (n=17), Dispensing/Distribution (n=5), Monitoring and Follow-Up (n=8), Practice Management (n=3), and Optimal-State Recommendations (n=4). Team leads from each of 9 participating sites focusing on OAA quality improvement were asked to share the anonymous assessment with team members at their sites who provide care to patients taking OAAs. All response choices were categorized as “never”, “sometimes”, or “always” for the degree to which the OAA standard is followed at the site. Frequency distributions are reported. Results: 105 clinicians (39 pharmacists, 34 nurses, 20 physicians, 10 NP/PAs, and 2 pharmacy technicians) completed the baseline self-assessment from 9 sites. Most standards had a response of “sometimes” or “always”. The area with the largest number of “always” was related to the completion of the OAA prescription. Of the 62 standards, 38 (61%) had at least 1 respondent select “never” and 4.5 respondents/standard (range 1 – 15) selected “never”. Standards that had the highest “never” responses were patient satisfaction monitoring (n=15), use of survivorship program for transition to primary care when appropriate (n=14), use of social determinants of health in OAA treatment decisions (n=13), documentation of treatment consent (n=12), use of therapeutics committee to determine place in therapy of OAAs (n=12), and use of collaborative practice agreements for pharmacists as part of the oncology care team (n=12). Conclusions: Adherence to OAA standards varied between the participating sites. A standardized baseline assessment evaluating current state is helpful in identifying gaps in care and targets for future quality improvement.

Impact of medically integrated pharmacies on oral anticancer medication prescription abandonment.

66 Background: Due to the high cost of oral anticancer medications, financial toxicity may limit patient access to treatment. Abandonment occurs when a patient does not fill a prescription. Higher out of pocket costs have been associated with higher rates of prescription abandonment of treatment across cancers with national abandonment rates typically reported as 18%. An integrated patient assistance process within the care team as occurs in a medically integrated pharmacy is postulated to lower abandonment rates. We measured prescription abandonment rates in the Texas Oncology (TXO) medically integrated pharmacy (MIP). Methods: We reviewed prescription data from the electronic health record (EHR) and our pharmacy dispensing system, for all new oral anticancer medications prescribed from January 2022 to December 2022. Prescriptions that were sent electronically from the EHR but did not have a corresponding dispense in the pharmacy dispensing software were classified as having a barrier to fill. Among the prescriptions that had a barrier to fill, we randomly selected cases for further detailed review to identify cause of barrier. By reviewing the EHR, we also examined whether patients filled any alternate oral or injectable anticancer agent within 60 days due to a formulary block, patient choice or physician choice. Abandonment was defined when patients did not receive their treatment or appropriate alternative treatment within 60 days of the written prescription date. Results: 17,442 prescriptions for oral anticancer medications were prescribed by Texas Oncology physicians. Of those 8460 were filled by the TXO MIP without extensive barriers. 8982 of prescriptions were not filled at our TXO MIP and of those 2895 (32%) prescriptions were further reviewed to determine cause of barrier to fill. 1435 (49.5%) prescriptions had a pharmacy benefit manager (PBM) design that routed the prescription to an external pharmacy and out of the continuity of care of the MIP. 827 (29%) of patients experienced financial toxicity and received free drug assistance with the help of the MIP patient assistance team. 72 (1.3 %) of patients were started on an appropriate alternative therapy with input from the medically integrated care team. 15 patients did not start their oral anticancer treatment which resulted in an abandonment rate of less than 1%. Conclusions: National abandonment is reported as high as 18% largely due to high out of pocket costs. The Texas Oncology MIP has a dedicated patient assistance team. Within the MIP, although 29% of patients had a financial barrier to fill, the prescription abandonment rate was <1%. Oral anticancer medications filled in the MIP led to decreased prescription abandonment due to the integrated patient assistance, pharmacy, and clinical teams. A medically integrated pharmacy should be the preferred approach for specialty cancer medications.

Selecting patient-reported outcome measures for a patient-facing technology.

This article provides insight into our process and considerations for selecting patient-reported outcome measures (PROMs) designed for self-reporting symptoms and quality-of-life among breast cancer (BCA) patients undergoing oral anticancer agent treatment via a patient-facing technology (PFT) platform. Following established guidelines, we conducted a thorough assessment of a specific set of PROMs, comparing their content to identify the most suitable options for studying BCA patients. We recommend utilizing the combination of EORTC QLQ-C30 + EORTC QLQ-BR45 as the preferred instrument, especially when developing a dedicated "breast cancer-only" application. When developing and maintaining a dashboard for a PFT platform that includes multiple cancer types, it is important to consider the feasibility of interface design and workload. To achieve this, we recommend using PRO-CTCAE+PROMIS 10 GH for the PFT. Moreover, it is important to consider adding ad hoc items to complement the chosen PROM(s). This article describes our efforts to identify PROMs for self-reported data while considering patient and developer burdens, providing guidance to PFT developers facing similar challenges in PROM selection.

Barriers and facilitators associated with implementing interventions to support oral anticancer agent adherence in academic and community cancer center settings.

The goal of this study is to determine barriers and facilitators to the implementation of medication adherence interventions to support cancer patients taking novel, targeted oral anticancer agents (OAAs). We conducted qualitative interviews using a semi-structured guide from the Consolidated Framework for Implementation Research (CFIR). We used purposive sampling to identify clinicians (physicians, pharmacists, nurse practitioners, nurses) and administrators (leadership from medicine, pharmacy, and nursing) who delivered care and/or oversee care delivery for patients with chronic leukemia prescribed an OAA. A total of 19 individuals participated in an interview (12 clinicians and 7 administrators), with 10 primarily employed by an academic cancer center; 5 employed by the community cancer center; and 4 employed by the integrated health-system specialty pharmacy. Barriers identified included low awareness of adherence interventions, difficulty in adherence measurement, complexity of designing and implementing a structured adherence intervention, and competing priorities. Facilitators identified included support of hospital administrators, value for pharmacists, and willingness to embrace change. Participants also made recommendations moving forward including standardizing workflow, designating champions, iterating implementation strategies, and improving communication between clinicians and with patients. Individual and system level factors were identified as determinants of implementation effectiveness of medication adherence interventions. A multidisciplinary advisory panel will be assembled to design comprehensive and actionable strategies to refine and implement a structured intervention to improve medication adherence in cancer patients.

A phase 1b study of E7386, a CREB-binding protein (CBP)/β-catenin interaction inhibitor, in combination with lenvatinib in patients with advanced hepatocellular carcinoma.

4075 Background: E7386, a novel oral anticancer agent, inhibits β-catenin binding to its transcriptional co-activator, CBP, thus modulating Wnt/β-catenin signaling. The objectives of the dose-escalation part in this phase 1b study were to assess safety, tolerability, pharmacokinetics (PK), biomarkers, and preliminary efficacy of E7386 combined with lenvatinib in patients with advanced hepatocellular carcinoma (HCC) or other solid tumors. Here, we present the results from the HCC subpart. Methods: In cycle 0, E7386 was administered orally in escalating doses once daily (QD) or twice daily (BID) for 5 or 6 consecutive days. From cycle 1 day 1, E7386 QD or BID, combined with daily oral lenvatinib (8 mg in patients with body weight of <60 kg or 12 mg in patients with body weight ≥60 kg), were administered on a continuous schedule in 28-day cycles in the HCC subpart. Adverse events (AEs) were graded using CTCAE v5.0. Prophylactic antiemetics were not allowed during the dose-limiting toxicities (DLT) evaluation period but were permitted after the occurrence of nausea and vomiting. Tumor response was assessed by investigators using mRECIST (Lencioni and Llovet, 2010). PK and biomarker analyses were conducted using samples collected at defined time points. Results: As of the cutoff date (9 December 2022), 25 patients had been treated in the HCC subpart with E7386 dose ranges from 10 to 80 mg QD and from 60 to 120 mg BID. Among 3 patients in the E7386 120 mg BID cohort, grade 3 maculopapular rash (in 1 patient) and grade 5 acute kidney injury (in 1 patient) DLTs were observed. No DLTs were observed in other cohorts. The most common treatment-emergent AEs (TEAEs; any grade) across all cohorts were nausea (n=19; 76.0%), vomiting (n=15; 60.0%), constipation (n=13; 52.0%), palmar-plantar erythrodysesthesia syndrome (n=12; 48.0%), diarrhea (n=11; 44.0%), and proteinuria (n=10; 40.0%). The most common grade ≥3 TEAEs (≥5% of patients) were proteinuria (n=5; 20.0%) and aspartate aminotransferase level increased (n=2; 8.0%). Nausea and vomiting were well controlled by a 5HT3 antagonist. Among the 25 treated patients, 9 (36.0%) partial responses (PRs) were observed, including 3 PRs in 10 patients who had received lenvatinib as a prior regimen. Cmax and AUC for E7386 increased with increasing E7386 dose. Conclusions: E7386 100 mg BID, in combination with lenvatinib (8 or 12 mg based on bodyweight) QD, was determined as the recommended phase 2 dose, and was deemed tolerable and manageable with antiemetic administration. The combination showed promising activity in patients with HCC, including those pretreated with lenvatinib. Clinical trial information: NCT04008797 .

Clinical Effect of the C-Reactive Protein to Serum Albumin Ratio in Patients with Metastatic Gastric or Gastroesophageal Junction Cancer Treated with Trifluridine/Tipiracil.

Trifluridine/tipiracil (FTD/TPI) is an oral anticancer agent used as a third- or later-line treatment for patients with metastatic gastric cancer/gastroesophageal junction cancer (mGC/GEJC). The C-reactive protein-to-serum albumin ratio (CAR) is an inflammation-based prognostic marker in gastric cancer. This retrospective study evaluated CAR's clinical significance as a prognostic factor in 64 patients with mGC/GEJC administered FTD/TPI as a third- or later-line therapy. Patients were categorized into high- and low-CAR groups based on pre-treatment blood data. This study evaluated associations between CAR and overall survival (OS), progression-free survival (PFS), clinicopathological features, treatment efficacy, and adverse events. The high-CAR group had significantly worse Eastern Cooperative Oncology Group performance status, a higher prevalence of patients administered with a single course of FTD/TPI, and a higher rate of patients not administered chemotherapy after FTD/TPI therapy than the low-CAR group. Median OS and PFS were significantly poorer in the high-CAR group than in the low-CAR group (113 vs. 399 days; p < 0.001 and 39 vs. 112 days; p < 0.001, respectively). In multivariate analysis, high CAR was an independent prognostic factor for OS and PFS. The overall response rate was not significantly different between the high- and low-CAR groups. Regarding adverse events, the high-CAR group had a significantly lower incidence of neutropenia and a higher incidence of fatigue than the low-CAR group. Therefore, CAR may be a potentially useful prognostic factor for patients with mGC/GEJC treated with FTD/TPI as third- or later-line chemotherapy.

Multiple cardiotoxicities during osimertinib therapy.

The tyrosine-kinase inhibitor osimertinib is an oral anti-cancer agent that is used for the treatment of patients with metastatic non-small cell lung cancer harbouring sensitising EGFR mutations. Patients receiving osimertinib are at higher risk of developing cardiac toxicity, and here we present the case of a 72-year-old male who developed multiple cardiotoxicities during therapy (i.e. QTc prolongation, atrial fibrillation, heart failure). A 72-year-old white British, ex-smoker male patient was admitted to our cancer centre with adenocarcinoma of the lung. Afatinib, gefitinib, osimertinib, and carboplatin plus pemetrexed chemotherapy were the treatments he received. At the 15th month of osimertinib therapy, the patient developed QTc prolongation. Two weeks after the first incidence of QTc prolongation, electrocardiography showed rate-controlled atrial fibrillation. In addition to his atrial fibrillation, echocardiography revealed severely impaired left ventricular systolic function (left ventricular ejection fraction: 30%). Baseline to osimertinib, an electrocardiography investigation was carried out as per the protocol. Baseline drug history was reviewed and rosuvastatin was discontinued before initiating osimertinib as both drugs contribute to QTc prolongation. Dabigatran, bisoprolol, and digoxin were started for the treatment of atrial fibrillation. Ramipril and spironolactone were prescribed for the treatment of heart failure but osimertinib continued uneventfully. The patient died of non-small cell lung cancer. Recommendations for practical and clinically relevant baseline and on-treatment assessments are considered which may reduce the risk of cardiac toxicity during osimertinib therapy. These include baseline cardiac risk stratification, consideration of concomitant medications that may result in additive cardiac risk, and use of electrocardiography and echocardiography surveillance.

Patient Reported Outcomes and Unscheduled Health Services use During Oral Anti-Cancer Treatment.

People on oral anti-cancer agents must self-manage their symptoms with less interaction with oncology providers compared to infusion treatments. Symptoms and physical function are key patient-reported outcomes (PROs) and may lead to unscheduled health services uses (urgent care and emergency department [ED] visits, hospitalizations), which in turn lead to increased health care costs. To evaluate the prediction of unscheduled health services uses using age, sex, and comorbidity, then determine the extent to which PRO data (symptoms and functioning) improve that prediction. This post-hoc exploratory analysis was based on data from the control group of a trial of medication adherence reminder and symptom self-management intervention for people starting a new oral anti-cancer agent (n=117 analyzed). Severity and interference with daily life for 18 symptoms, physical function, and depressive symptoms were assessed at intake (oral agent start), and four, eight, and 12 weeks later. Unscheduled health services use during three four-week periods after the start of oral agents was analyzed using generalized mixed effects models in relation to age, sex, comorbidity, and PROs at the beginning of each time period. The summed severity index of 18 symptoms and physical function were significant predictors of hospitalizations in the four weeks following PRO assessment. The addition of PROs improved areas under the receiver operating characteristic curves to be over .70 in most time periods. Monitoring of PROs has the potential of reducing unscheduled health services use if supportive care interventions are deployed based on their levels.

A phase 1 study of E7386, a CREB-binding protein (CBP)/β-catenin interaction inhibitor, in patients (pts) with advanced solid tumors including colorectal cancer: Updated dose-escalation part.

106 Background: E7386 is a novel oral anticancer agent that inhibits the binding of β-catenin to its transcriptional co-activator, CBP, thereby modulating Wnt/β-catenin signaling. In preclinical studies, E7386 showed promising activity (eg, modulation of tumor angiogenesis, alteration of the immune microenvironment, and inhibition of tumor growth). At a prior cutoff point for the dose-escalation part of a phase 1 study of E7386 in pts with advanced solid tumors, we reported 2 dose-limiting toxicities (DLTs; both grade 3 decreased appetite) with E7386 160 mg twice daily (BID). Here we describe an update of the dose-escalation part of this phase 1 study—we mainly report updated safety, tolerability, and preliminary efficacy and biomarker results, which led to the inclusion of an additional dose level for investigation in the expansion part of this study. Methods: E7386 was administered orally in escalating doses on a BID continuous schedule in 28-day cycles. Adverse events (AEs) were graded using CTCAE v5.0. Tolerability was judged by DLTs during cycle 1 (C1). Tumor response was assessed every 8 weeks from C1 day (D) 1, or sooner if clinically indicated, and at the end of treatment by investigators using RECIST v1.1. Samples for pharmacokinetic analyses were collected on C1D1 and C1D8; samples for biomarker analyses were collected at protocol-defined time points. To determine the appropriate dose(s) for the expansion part of this study, additional investigation of the dose-escalation part was conducted. Results: As of the data cutoff (DCO) date (30 June 2022), 36 pts (24 men, 12 women; median age, 61.5 y) were enrolled in E7386 dose cohorts (10 to 160 mg BID). Doses were tolerable up to 120 mg BID. The most common treatment-related AEs (all grades; &gt; 10%) were nausea (80.6%), vomiting (58.3%), aspartate aminotransferase increased (16.7%), and alanine aminotransferase increased, decreased appetite, and diarrhea (13.9% each). Nausea and vomiting were well-controlled with antiemetics such as 5HT3 antagonists, except in the 160 mg BID cohort. Two pts with a Wnt-related adenomatous polyposis coli (APC)- mutation (small bowel adenocarcinoma and desmoid tumor) showed a partial response. As of the DCO date, 2 pts (who continued on-treatment as of that date) had received over 1.5 y of E7386 treatment. The preliminary PK analysis showed plasma exposure of E7386 generally increased with an increasing dose over the assessed dose range. FGF21 levels in plasma increased following E7386 administration. Conclusions: E7386 120 mg BID was tolerated and determined as the recommended dose for the expansion part. Based on additional analyses of the dose-escalation part of this study, further investigation of safety, preliminary efficacy, PK, and biomarker analyses of E7386 is ongoing using 2 dose levels (100 and 120 mg BID) in the expansion part. Clinical trial information: NCT03833700 .