Oral Target Therapy Research Articles

Abstract PO3-27-10: Financial Stress and Care Disruption in Breast Cancer: A Ten-Year National Health Interview Survey Analysis

Abstract Background: Financial stress is an adverse event of BC. Increased availability of oral targeted therapy (OTT) is hypothesized to add to this burden. We assess financial stress at the population level as a function of availability of OTT. Design: We used 2013-2022 NHIS adult BC population data. Financial stress markers were care disruption, food insecurity and percent home ownership. Care disruption was defined as at least 1 event of skipping or taking less medication or delayed filling or unable to afford prescriptions. Available oral therapy Florida Blue July 2023 was cross-referenced with the NCI targeted therapy list for breast cancer as of July 2023. Initial FDA approval date for breast cancer for OTT determined the number of available OTT by survey year. We conducted a time-adjusted logistic regression to account of external effects such as COVID and adjusted for sociodemographics. Results: In a population of over 30 million respondents with BC, care disruption affected < 10%; food insecurity, < 1.3%, >83% reported home ownership. The number of available OTT did not affect outcomes. Survey year was associated with reduced care disruption (adjusted OR 0.82, 95% CI 0.68–0.99). Self-reported Black race affected home ownership (aOR 0.57, 95% CI 0.43-0.77) and any care disruption (a2.11, 95% CI 1.38-3.24). Non-White patients more likely reported food insecurity (aOR 5.56, 95% CI 2.58-12.01). Income < 200% of poverty level negatively affected outcomes. Stroke (aOR 1.97, 95% CI 1.09-3.55) and heart attack (aOR 2.10, 95% CI 1.11–4) history increased likelihood of care disruption. Conclusion: Available number of OTT did not influence financial stress in a BC population. Adverse sociodemographics and comorbidities correlated with care disruption. Our study was limited by absence of actual OTT use; further assessment at the individual level is needed. Table. Outcomes Citation Format: Maya Doyle, Erina Quinn, Sarah Bell, Braelyn Wekwerth, Ruth Carlos. Financial Stress and Care Disruption in Breast Cancer: A Ten-Year National Health Interview Survey Analysis [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO3-27-10.

Immunogenicity of COVID-19 vaccines in lung cancer patients

ObjectivePatients with lung cancer are at increased risk of SARS-CoV-2 infection and severe complications from COVID-19, but information on the efficacy of anti-SARS-CoV-2 vaccine in these patients is scarce. We aimed at evaluating the safety and immunogenicity of COVID-19 vaccines in this population. Patients and methodsThe prospective, nationwide SOLID substudy, enrolled adults with lung cancer who were fully vaccinated against COVID-19. Serum anti-SARS-CoV-2 IgG antibody levels were quantitatively assessed two weeks and six months after receipt of the last dose using a chemiluminescent microparticle immunoassay. Multivariate odds ratios for the association between demographic and clinical factors and seronegativity after vaccination were estimated. Results1973 lung cancer patients were enrolled. Most patients had stage IV disease (66%) and were receiving active cancer treatment (82.7%). No significant differences were found in the probability of being seronegative for anti-SARS-CoV-2 IgG antibodies after full vaccination between patients who were receiving active cancer treatment and those who were not (p = 0.396). The administration of immunotherapy or oral targeted therapy and immunization with mRNA-1273 COVID-19 vaccine were factors independently associated with increased odds of being seropositive after vaccination. From all patients, 1405 received the second dose of vaccine and high levels of antibody titers were observed in 93.6% of patients two weeks after second dose. At six months, multivariate logistic regression analysis showed that performance status ≥ 2 was independently associated with a higher probability of being seronegative after full vaccination with an OR 4.15. On the other hand, received chemotherapy or oral target therapy and vaccination with mRNA-1273 were a factor independently associated with lower odds of being seronegative after full vaccination with an OR 0.52, 0.37 and 0.34, respectively. ConclusionsLung cancer patients can safely achieve a strong immune response against SARS-CoV-2 after full vaccination, regardless of the cancer treatment received. Trial registrationNCT04407143.

17th International Conference on Malignant Lymphoma, Palazzo dei Congressi, Lugano, Switzerland, 13 - 17 June, 2023.

Background: While oral targeted therapies (OTT) have transformed the care of patients (pts) with lymphoma, adherence, cost, and chronic low-grade toxicities with subsequent impact on health-related quality of life (HRQoL) remain challenging issues. There are limited data on HRQoL in older adults (OA), who tend to be more vulnerable to treatment-related adverse effects. We prospectively evaluated the role of geriatric assessment (GA) in predicting HRQoL and adherence in OA with lymphoma on OTT. Methods: Pts ≥70 years (yrs) with lymphoma, initiating or already on OTT were included. A GA was performed at baseline; pt, disease, and OTT characteristics were recorded. Pts were followed monthly for the first 3 months (mos), then every 3 mos for 1 year. QoL was measured at each visit using the European Organization for Research and Treatment of Cancer Quality of Life Questionnaires Core 30 (EORTC QLQ-C30) and EORTC QLQ- chronic lymphocytic leukemia 16 (EORTC QLQ-CLL16) modules. The log QoL scores were modeled as a function of visit and mean scores at 12 months were compared to baseline using a linear mixed model. Results: We enrolled 50 pts. Median age was 77 yrs (70–93 yrs) with 88% pts having at least 1 geriatric syndrome (GS), including cognitive impairment (22%), depression (24%), polypharmacy (86%) and falls (16%); 50% pts had ≥2 GS; 50% having an impaired 4-meter gait speed (<1 m/s); 46% having an abnormal timed-up-and-go (TUG) time (>10s) and 86% had an adjusted CIRS-G score of ≥6. OTT included ibrutinib (54%), venetoclax (26%) and acalabrutinib (12%). At baseline, advancing age, activities of daily living (ADL) dependence, and instrumental activities of daily living (IADL) dependence were associated with inferior global health status, physical functioning, role functioning, and cognitive functioning scores. IADL dependence was also associated with worse social functioning and most symptoms scores. An abnormal TUG was associated with lower global health score (p = 0.002) and cognitive functioning (p = 0.003). At the end of 1 year, there was a statistically significant worsening of global health status (mean difference -8.4, p = 0.003) without any changes in other functional scales; however, it did not reach the predefined criterion for clinical relevance (absolute difference of >10, Figure 1). Only impaired baseline TUG was associated with significant worsening of global health status (-1.9 vs. -23.2, p = 0.048), physical (4.1 vs. -8.2, p = 0.031), role (1.3 vs. -18.5, p = 0.026) and social functioning (5.1 vs. -24.1, p = 0.016), and increasing fatigue scale (-11.5 vs. 20.4, p < 0.001) over 1 year. Other geriatric impairments did not impact changes in HRQoL over time. The research was funded by: Roswell Park Alliance Foundation Keywords: Cancer Health Disparities, Molecular Targeted Therapies Conflicts of interests pertinent to the abstract. P. Torka Consultant or advisory role: Genenetech, GenMab, Lilly USA, Seagen

Impact of Fixed-Duration Oral Targeted Therapies on the Economic Burden of Chronic Lymphocytic Leukemia in Canada.

Continuous oral targeted therapies (OTT) represent a major economic burden on the Canadian healthcare system, due to their high cost and administration until disease progression/toxicity. The recent introduction of venetoclax-based fixed-duration combination therapies has the potential to reduce such costs. This study aims to estimate the prevalence and the cost of CLL in Canada with the introduction of fixed OTT. A state transition Markov model was developed and included five health states: watchful waiting, first-line treatment, relapsed/refractory treatment, and death. The number of CLL patients and total cost associated with CLL management in Canada for both continuous- and fixed-treatment-duration OTT were projected from 2020 to 2025. Costs included drug acquisition, follow-up/monitoring, adverse event, and palliative care. The CLL prevalence in Canada is projected to increase from 15,512 to 19,517 between 2020 and 2025. Annual costs were projected at C$880.7 and C$703.1 million in 2025, for continuous and fixed OTT scenarios, respectively. Correspondingly, fixed OTT would provide a total cost reduction of C$213.8 million (5.94%) from 2020 to 2025, compared to continuous OTT. Fixed OTT is expected to result in major reductions in cost burden over the 5-year projection, compared to continuous OTT.

The Economic Impact of Treatment Sequencing in the Management of Chronic Lymphocytic Leukemia in Canada Using Venetoclax Plus Obinutuzumab

Introduction: In the management of patients with chronic lymphocytic leukemia (CLL), oral targeted therapies (OTT) represent a significant advancement. However, for most Canadian public and private payers, their high cost raises concerns about financial impact & affordability. In part, this burden is associated with new expensive OTT that are used on a continuous basis until disease progression or unacceptable toxicity. The introduction of venetoclax-based combinations administered for a fixed duration offers new options for CLL patients with the potential to achieve long remission with manageable side effects for a limited period, and most importantly time off therapy. From a Canadian healthcare system perspective, fixed treatment duration would have the potential to offer better budget predictability and reduced costs. Venetoclax in combination with obinutuzumab (VO) is a fixed duration treatment (12 months) recently approved in Canada, with the potential to reduce the cost burden of treating CLL. The primary objective of this project was to estimate the total cumulative cost per patient of different treatment sequences for adults with CLL, considering first line (1L) and subsequent treatments, over a 10-year time horizon, from a Canadian healthcare system perspective. A secondary objective was to evaluate the economic impact of introducing sequences of treatment with VO in 1L, compared to other sequences of treatment without VO. Methods: A 10-year partitioned survival model was developed to assess the economic impact of different treatment sequences in CLL. Five health states were included: 1L, second line (2L), third line (3L), supportive care and death. The total number of treatment sequences considered was limited to 100. Key clinical parameters, including progression-free survival and overall survival data, were extracted from pivotal clinical trials of each selected treatment. Analyses were conducted from a Canadian health-care system perspective; accordingly, only direct medical costs were considered, including treatment acquisition costs, administration costs, follow-up and monitoring costs, cost of tumour lysis syndrome prophylaxis, cost of adverse events as well as cost of supportive care. All results were stratified by TP53 aberration. Results: Total 10-year cumulative costs of treatment sequences starting with each 1L treatment are summarized in Table 1. Overall, treatment sequences starting with VO had lower 10-year cumulative costs compared to sequences starting with other novel agents (i.e., ibrutinib [IBRU] or acalabrutinib [ACAL]). Among patients without TP53 aberration, cumulative costs per patient of sequences starting with VO ranged from $327,574 to $418,213, whereas sequences starting with IBRU or ACAL monotherapy ranged from $772,127 to $930,700 [Figure 1]. Similarly, in adults with TP53 aberration, cumulative costs per patient of sequences starting with VO ranged from $500,639 to $536,507, and sequences starting with IBRU or ACAL monotherapy ranged from $770,737 to $862,554. Cumulative costs for treatment sequences were largely determined by the first two lines of treatment. When comparing treatment sequences with the same 1L therapy, sequences with continuous novel therapies in 2L (e.g., ACAL monotherapy) resulted in higher costs compared to sequences with fixed duration (e.g., venetoclax in combination with rituximab). For patients without TP53 aberration, the economic impact of treating all patients with VO led to savings of $169,341 per patient, over 10 years compared to any other 1L treatment, for the Canadian healthcare system. Savings over 10 years were even higher ($293,731) for patients with TP53 aberration. Although TP53 patients are preferably treated with expensive continuous OTT, VO, a fixed duration OTT, also demonstrates a clear and indisputable therapeutic value in this patient population, with a progression-free survival of 40.6% at 60 months; therefore, making VO available to all patients considerably increases cost savings. Conclusions: Treatment sequences starting with VO regimen in 1L resulted in lower costs compared to sequences starting with other novel agents administered until disease progression. These savings are mainly due to substantial reductions in treatment costs associated with a fixed treatment duration. Figure 1View largeDownload PPTFigure 1View largeDownload PPT Close modal

A Qualitative Exploration of Medication Experience and Factors Contributing to Adherence to Oral-Targeted Therapy Among Lung Cancer Survivors

ObjectivesThe introduction of oral-targeted therapy for cancer improves survival while adherence also presents as a challenge to patients. Current studies on oral anticancer agents are primarily limited to patients from developed countries with breast cancer and chronic myeloid leukemia receiving oral chemotherapy and hormonal therapy. This study explored experience of oral-targeted therapy adherence among Chinese patients with nonsmall cell lung cancer and its contributing factors by using a qualitative research. Data SourcesSemi-structured interviews with 16 patients and 7 family caregivers at a tertiary tumor hospital in China were conducted to understand their experience and perceptions of oral-targeted therapy. Thematic analysis was applied to generate the themes and to identify underlying factors associated with the adherence. ConclusionThe lung cancer survivors struggled with ambivalence between survival and relief during taking targeted anticancer medication and showed diverse models of nonadherence, including intentionally or unintentionally intermittent medication and overadherence. Three main themes were identified: (1) cancer-related distresses, (2) inadequate social support, and (3) forgetfulness, together with seven subthemes, representing factors impeding patients’ medication adherence. The themes demonstrate complicated and interrelated factors from personal, interpersonal, sociocultural, and structural forces contributing to patients’ poor adherence. Implications for Nursing PracticeThe findings suggest the imperativeness of reinforcing community- or home-based oral-targeted medication management in which nurses play a principal role to implement strategies of patient education, symptom management, reminder prompts, and monitoring to improve adherence.

Discordance in management of adverse events associated with oral therapies in hormone receptor–positive breast cancer among health care providers and experts: Findings from an online decision support tool.

382 Background: Oral targeted therapies (OTTs) inhibiting CDK4/6, PI3K, and mTOR have established roles across multiple lines of therapy in patients with advanced hormone receptor–positive, HER2-negative breast cancer (HR+ BC). Abemaciclib, a CDK4/6 inhibitor (i), now also is approved in the adjuvant setting for eligible patients with early-stage HR+ BC. These OTTs are associated with various adverse events (AEs), such as cytopenias, diarrhea, hepatotoxicity, and rash. Optimal AE management is critical to promote patient adherence and achieve the best possible outcomes. Here we report an analysis of healthcare professional (HCP) management of AEs associated with OTTs in HR+ BC using an online decision support tool. Methods: The online tool was developed with 5 BC experts providing recommendations on the management of AEs associated with OTTs. Within the online tool, HCPs were prompted to input relevant patient case details through a series of predefined questions, including which OTT and type of AE the patient is experiencing, along with their management approach. Participants were then shown an expert recommendation based on the specific characteristics of that case and were asked if their management plan changed based on that recommendation. Results: Between September 2021 and April 2022, 557 cases were entered by 390 participants. Among 291 cases of patients currently receiving oral therapy, CDK4/6i therapy was most commonly selected (82%), followed by PI3Ki (11%) and mTORi (8%) therapy. The most common AE reported for CDK4/6i, PI3Ki, and mTORi therapy were cytopenias (56%), hyperglycemia (64%), and stomatitis (57%), respectively. With CDK4/6i, HCPs were discordant with expert recommendations for management of AEs reported in 44%, 39%, and 35% of entered cases with ribociclib, abemaciclib, and palbociclib, respectively. The greatest variance between HCP and expert recommendations were with management of VTE, hepatotoxicity, QT prolongation, and rash (Table). Among HCPs with discordant results from the experts, 50% changed their AE management plan after viewing the expert recommendation. Conclusions: These data suggest that HCPs may be challenged to optimally manage AEs related to OTTs in patients with HR+ BC. Use of an online tool may enhance HCP management of these AEs for patients with HR+ BC. A detailed analysis of the tool, including HCP planned management vs expert recommendations, will be presented.[Table: see text]

Impact of the app-based and nurse-led supportive care program AKO@dom on dose intensity of oral-targeted therapies in patients with metastatic renal cell cancer: a multicentric observational retrospective study.

Tyrosine kinase inhibitors (TKIs) remain a cornerstone of metastatic kidney cancer (mRCC). Adverse events (AEs) may lead to dose downregulation, and optimal management of AEs is needed to maintain an efficient dose intensity (DI). The aim of our study was to evaluate the impact of an app-based and nurse-led supportive-care program on DI in mRCC patients. This multicenter (n = 3), retrospective study evaluated all consecutive mRCC patients who participated in the AKO@dom program, which consisted of an app-based and nurse-led weekly patient evaluation at home during the first 3months of TKI intake. Treatment patterns and modifications were described, and the mean DI (mDI) was calculated at the end of AKO@dom. Eighty-nine patients were included: 12 had sunitinib, 18 pazopanib, 12 axitinib, and 47 cabozantinib. Median age was 69years (60-76). TKIs were mainly initiated at standard doses except for cabozantinib (53% started at 40mg/day); 71% had prior systemic treatment. Nine patients discontinued permanent treatment during the program. Thirty-two patients required ≥ 1 dose interruption, and 29% experienced ≥ 1 grade 3 AE of any type. The mDI (in mg/day) at 3months was 34.4 ± 17.7 for sunitinib, 672.8 ± 144 for pazopanib, 8.6 ± 2.6 for axitinib, and 40 (36-48) for cabozantinib. Fifty-five patients [68.75% (95% CI: 57-78%)] had a mDI ≥ than reported in the literature. Overall survival at 12months was 64.2% (CI 95%: 55-75%). The AKO@dom program allowed 68.75% of patients to maintain a high dose intensity after 3months of TKI treatment. The impact on survival outcomes needs to be evaluated in randomized clinical trials.

Pharmacokinetic Variability Drives Palbociclib-Induced Neutropenia in Metastatic Breast Cancer Patients: Drug-Drug Interactions Are the Usual Suspects.

Palbociclib is a good candidate for therapeutic drug monitoring (TDM) due to its narrow therapeutic range and frequency of toxicities, particularly high-grade neutropenia. In this prospective, bicentric clinical trial, we evaluated the palbociclib exposure–toxicity relationship and determined the relevant sources of palbociclib pharmacokinetic variability, including drug–drug interactions (DDI). We followed 58 patients (mean age: 62.9 years) for 1 year. The geometric median of palbociclib plasma trough concentration (Ctrough) was 74.1 ng/mL. Neutropenia occurred in 70.7% of patients (high grade in 67.2% of patients). High-grade neutropenia occurrence during the first two palbociclib cycles was higher in patients with lower neutrophil count at initiation (p = 0.002). Palbociclib plasma Ctrough was correlated with high-grade neutropenia occurrence during the first two cycles (p = 0.024, OR 5.51). Co-treatment with agents that may interfere with palbociclib PK significantly influenced palbociclib Ctrough (p < 0.05). CYP3A4/P-glycoprotein inhibitors increased by 25% palbociclib Ctrough (p = 0.035), while antacids reduced it by 20% (p = 0.036). However, DDI did not have any significant effect on high-grade neutropenia occurrence (p > 0.05). This study confirms the major role of TDM to manage palbociclib safe use from the first week of treatment, particularly the significant incidence of hematological toxicity. Moreover, this first dedicated prospective study confirmed the importance of characterizing co-treatments to limit the DDI risk with oral-targeted therapies.

Oral targeted therapy dose adaptation in older patients with cancer: A real-life French cohort.

Oral targeted therapies (OTTs) are widely used for cancer management. However, there is no consensus on OTT dose adaptation in older patients with cancer. This noninterventional, retrospective study was a real-life assessment of dose adaptation for six OTTs (afatinib, everolimus, palbociclib, pazopanib, sorafenib and sunitinib), at baseline and during treatment, and the reasons for the changes, in ≥70-year-old patients treated between February 2016 and August 2019. Data were compared with univariate models fitted with all variables. Among the 986 patients treated with OTT, the group of ≥70-year-old patients (n = 122) received afatinib (15.6%), everolimus (14.8%), palbociclib (50.8%), pazopanib (9.8%), sorafenib (5.8%) or sunitinib (3.2%). At baseline, the prescribed OTT dose was adapted (reduction) in 29% of ≥70-year-old patients (35/122). These 35 patients were significantly older (mean age 80 vs 74 years, P < .001), and more frequently had a performance status score ≥2 (P < .01) than the other patients (n = 87). In the standard dose group, higher toxicity grades (P = .18) and subsequent dose reduction (41% of patients, 36/87) tended to be more frequent compared with the baseline adapted dose group (26%, 9/35, P = .1). At the study end, 53% of patients in the whole cohort (65/122) were taking a lower dose than the recommended one. At OTT initiation, dose was adapted in 29% of older adults with cancer, rarely after a formal oncogeriatric evaluation (6.5% of all patients). In the absence of recommendations, clinical studies are needed to evaluate the efficacy and safety of baseline OTT dose reduction in older adults with cancer.

Comparison of Approaches for Measuring Adherence and Persistence to Oral Oncologic Therapies in Patients Diagnosed with Metastatic Renal Cell Carcinoma

Adherence and persistence studies face several methodologic difficulties, including short-term mortality. We compared approaches to quantify adherence and persistence to first line (1L) oral targeted therapy (TT) in patients diagnosed with metastatic renal cell carcinoma (mRCC). Patients with mRCC ages 66 years or more who initiated TTs within 4 months of diagnosis were identified in the Surveillance, Epidemiology, and End Results Medicare-linked database (2007-2015). Adherence [proportion of days covered (PDC) >80%] was calculated using (i) PDC with a fixed 6-month denominator including then excluding patients who died within the 6 months and (ii) PDC with a denominator measuring time on treatment. Risk of nonpersistence was obtained by censoring death or treating death as a competing risk using cumulative incidence functions. Among 485 patients with mRCC initiating a 1L oral TT (sunitinib, 64%; pazopanib, 25%; other, 11%), 40% died within 6 months. Adherence was higher after restricting to patients who survived (60%) compared with including those patients and assigning zero days covered after death (47%). Risk of nonpersistence was higher when censoring patients at death, 0.91 [95% confidence interval (CI), 0.88-0.94], compared with treating death as a competing risk, 0.75 (95% CI, 0.71-0.79). Different approaches to handling death resulted in different adherence and persistence estimates in the metastatic setting. Future studies should explicitly report the proportion of patient deaths over time and explore appropriate methods to account for death as competing risk. Use of several approaches can provide a more comprehensive picture of medication-taking behavior in the metastatic setting where death is a major competing risk.

Evaluating the Role of Baseline Geriatric Assessment in Predicting Quality of Life in Older Adults with Non-Hodgkin Lymphoma on Oral Targeted Therapies

Background:Oral targeted therapies (OTT) have transformed the care of patients with non-Hodgkin lymphoma (NHL) with significantly improved survival outcomes compared to chemo-immunotherapy. While data from clinical trials suggest improvement in global health and some symptom scores, there is limited data on health-related outcomes in older adults who are more vulnerable to treatment-related adverse effects. Geriatric assessments can predict chemotherapy-related toxicity in older adults and the presence of geriatric impairments is associated with inferior quality of life. The role of geriatric assessment (GA) in predicting health-related quality of life (HRQoL) and treatment toxicity in patients with NHL on OTT is unknown. In this prospective study, we describe the association between OTT and HRQoL in older adults with NHL. We further describe the relationship between baseline geriatric assessment and longitudinal HRQoL parameters.Methods:We included patients (pts) ≥70 years (yrs) of age with NHL, initiating or already receiving OTT. A GA, including assessment of function, depression, cognition, physical performance and comorbidities, was performed at baseline. Pts were followed monthly for the first 3 months (mos), then every 3 mos for 1 year. Quality of life (QoL) was measured at each visit using the European Organization for Research and Treatment of Cancer Quality of Life Questionnaires Core 30 (EORTC QLQ-C30) and EORTC QLQ - chronic lymphocytic leukemia 16 (EORTC QLQ-CLL16). The log QoL scores were modeled as a function of visit and mean scores at 6 months were compared to baseline using a linear mixed model. A change in score of >10 was considered clinically significant based on previous work.Results:We enrolled 25 pts with a median age of 77 yrs (71-93 yrs). Median follow up was 6.3 mos (range, 2.7-8.8 mos). The most common diagnosis was chronic lymphocytic leukemia (n=21) followed by mantle cell lymphoma (n=3) and marginal zone lymphoma (n=1). Most pts (72%) were on OTT at study entry and the most frequently used OTTs were ibrutinib (n=17) and venetoclax (n=5). GA revealed the presence of a geriatric syndrome (GS) in more than 90% of pts, including cognitive impairment (28%), depression (24%), polypharmacy (92%) and recent falls (12%); 48% of pts had ≥2 GS. Nine pts (36%) had impaired 4-meter gait speed and/or timed-up-and-go (TUG); 20 pts (80%) had an adjusted CIRS-G score of ≥6. At baseline, dependence in independent activities of daily living (IADL) was associated with inferior global health status scores (69.1 vs 86.1, p=0.023) and physical functioning scores (66.7 vs 88.1, p=0.008). Similarly, an abnormal TUG (>10 seconds) was associated with a lower global health score (71.3 vs 86.1, p=0.037). Dependence in 2 or more activities of daily living (ADL) was also associated with lower baseline physical functioning scores (57.8 vs 88.0, p=0.003) and role functioning scores (61.1 vs 90.8, p=0.030). During the 6-month follow up, there was significant worsening of global health status (mean difference -5.4, p=0.024) and cognitive functioning scores (mean difference -9.6, p<0.001) in the entire cohort. There were no changes in other functional scales (physical, role, emotional and social functioning, fatigue scale, infection scale, social problems and future health) over time (Figure 1). Trends in symptom scores were mixed with improvement in some scores (pain, fatigue) and worsening of others (dyspnea, diarrhea, constipation), none of which met the predefined criteria for clinical relevance (absolute difference of >10). Presence of various geriatric impairments at baseline did not impact changes noted in global health, physical, emotional, social and role functioning over time. Interestingly, we found a greater improvement in symptom scores in patients with baseline impairments in IADL (fatigue, pain), ADL (pain) and a CIRS-G score of ≥6 (insomnia).Conclusion:The presence of geriatric syndromes is common in older adults with NHL with almost half of the patients in our cohort with ≥2 GS. Older adults with GS had lower baseline global health status and physical functioning scores but experienced greater improvement in symptoms scores and maintenance of longitudinal HRQoL than those without GS at baseline. Chronological age had no impact on baseline or longitudinal HRQoL, underscoring the need to incorporate GA into clinical practice rather than relying on age alone. [Display omitted] DisclosuresWildes: Janssen: Consultancy; Carevive: Consultancy; Seattle Genetics: Consultancy; Sanofi: Consultancy. Torka: TG Therapeutics: Membership on an entity's Board of Directors or advisory committees.

Sequencing Therapy in Chronic Lymphocytic Leukemia (CLL): Treatment Patterns and Associated Outcomes in Community Practice for Patients with Relapsed/Refractory CLL in the United States

Background: CLL is the most common type of leukemia in adults in the US. Traditionally, chemotherapy (CT) and chemoimmunotherapy (CIT) have been the treatment mainstay, with new oral-targeted options recently becoming available. CLL patients (pts) who relapse and/or are refractory to their initial treatment have poorer outcomes compared with pts who are treatment naive, especially if they harbor high-risk genetic features (eg, 17p deletion [del(17p)]). As oral-targeted therapies became available in the US for pts with CLL, including those positive for del(17p), treatment patterns have changed. However, questions about how to sequence new therapies and traditional CIT/immunotherapy (IT) remain.Aims: This study used an electronic health record database to characterize treatment sequencing and associated outcomes in relapsed/refractory (R/R) CLL pts. The association between treatment choices and outcomes stratified by del(17p) status and previous line of therapy (LoT) was also explored.Methods: This was a retrospective observational study in CLL utilizing a large, longitudinal, demographically and geographically diverse database of US cancer pts (Flatiron Health 06/2017). An analytic cohort of pts treated mostly at community practice sites who initiated a LoT after Jan 2014 was developed. Time to next LoT or death (TTNLD), defined as the start date of a LoT to the start date of next LoT or death or the date of data cut, whichever comes first, was analyzed by Kaplan-Meier method. A Cox proportional hazard model was used for unadjusted and adjusted analyses including hazard ratios (HR) estimation.Results: The analytic cohorts included 1,457 and 613 pts who initiated 2nd and 3rd LoT with either B-cell receptor or B-cell lymphoma 2 (BCR/BCL2) inhibitor or CT/CIT/IT after Jan 2014. Average age at CLL diagnosis was 64.8 years (64.0 years); 61.6% (60.7%) of pts were male; and 72.2% (71.8%) were Caucasian (2nd LoT, 3rd LoT, respectively). A subcohort included 374 pts who received either BCR/BCL2 or CT/CIT/IT as 2nd LoT following initial CT/CIT/IT. Among these 374 pts, 161 (43.0%) were treated with a BCR/BCL2 inhibitor; 213 (57.0%) were treated with CT/CIT/IT for the 2nd LoT. The rate of del(17p)-specific testing before initiation of 2nd LoT was 67.1%, and 68.4% before the initiation of 3rd LoT.Median TTNLD in del(17p)-negative pts who initiated 2nd LoT with a BCR/BCL2 inhibitor was not reached (proportion of pts who experienced TTNLD at 06/2017 was less than 50%; Figure 1) vs 21.5 months in pts who initiated 2nd LoT with CT/CIT/IT; similarly, for del(17p)-positive pts: 28.3 months with BCR/BCL2 inhibitors vs 9.8 months for CT/CIT/IT. Pts treated with a BCR/BCL2 inhibitor had a lower risk of advancing to subsequent LoT than pts treated with CT/CIT/IT (HR 0.56; 95% CI: 0.47-0.67 [Figure 1, Table]).Median TTNLD in del(17p)-negative pts who initiated 3rd LoT with a BCR/BCL2 inhibitor was 31.6 vs 12.2 months in pts who initiated 3rd LoT with CT/CIT/IT; similarly, for del(17p)-positive pts: 12.6 months with BCR/BCL2 inhibitors vs 5.5 months for CT/CIT/IT. The HR for advancing from 3rd LoT to subsequent LoT was 0.46 (95% CI: 0.36-0.58) for pts treated with a BCR/BCL2 inhibitor compared with CT/CIT/IT (Figure 2, Table).Pts who were treated with 2nd-line BCR/BCL2 inhibitor following CT/CIT/IT had a median TTNLD that was not reached, significantly longer than the median TTNLD in pts who had CT/CIT/IT after initial CT/CIT/IT (median 26.6 months; HR 0.52; 95% CI: 0.35-0.78).Conclusion: In this real-world analysis of treatment pattern of CLL pts, regardless of del(17p) status or LoT (2nd or 3rd), R/R CLL pts receiving an oral-targeted therapy had a longer TTNLD compared with pts receiving CT/CIT/IT. In particular, pts receiving a BCR/BCL2 inhibitor as subsequent LoT to initial treatment with CT/CIT/IT had a longer TTNLD than pts receiving CT/CIT/IT following CT/CIT/IT. [Display omitted] DisclosuresKapustyan:AbbVie Inc.: Employment, Equity Ownership. Keim:AbbVie Inc.: Employment, Equity Ownership, Other: I am an employee of AbbVie, Inc and may own AbbVie and/or Abbott stock. Meissner:AbbVie Inc.: Employment, Equity Ownership, Other: I am an employee of AbbVie, Inc and may own AbbVie and/or Abbott stock. Nielsen:AbbVie Inc.: Employment, Equity Ownership. Zhang:AbbVie Inc.: Employment, Equity Ownership. Jiang:AbbVie Inc.: Employment, Equity Ownership.

Evaluating the role of baseline geriatric assessment in predicting adherence to oral targeted therapies and outcomes in older adults with non-Hodgkin lymphoma.

12043 Background: Oral targeted therapies (OTT) have transformed the treatment landscape of Non-Hodgkin lymphoma (NHL). However, measuring, defining and optimizing adherence to OTT remains a challenge. Prior studies have reported variable adherence rates (12-100%) to OTT in cancer patients (pts), with suboptimal adherence associated with inferior outcomes. In older adults (OA), geriatric syndromes (GS) such as polypharmacy and cognitive impairment can impact adherence. While geriatric assessment (GA) can predict chemotherapy-related toxicity in OA, its utility in NHL pts on OTT is unknown. In this pilot study, we evaluate the role of GA in predicting adherence and outcomes in NHL pts on OTT. We also report the feasibility of using MEMS Cap, an electronic event monitoring system, to measure adherence in this population. Methods: Pts ≥70 years (yrs) with NHL, initiating/receiving OTT were included. A GA was performed at baseline; pt, disease, and OTT characteristics were recorded. Pts were followed monthly for the first 3 months (mos), then every 3 mos for 1 year. Primary endpoint was treatment adherence rate, measured using both subjective [brief adherence rating scale (BARS)] and objective (pill counts and MEMS cap) methods. Progression free survival (PFS) was measured from time of therapy initiation to disease progression or death. Results: Of the 54 pts screened, 25 were enrolled. Median age was 77 yrs (71-93 yrs), 21 pts had chronic lymphocytic leukemia, 3 had mantle cell lymphoma and 1 had marginal zone lymphoma. Most frequently used OTT were ibrutinib (n = 17) and venetoclax (n = 5). Most pts (72%) were on OTT at study entry. Median time on therapy was 16.4 mos (1.9-44.6 mos). GS included cognitive impairment (28%), depression (24%), polypharmacy (92%) and recent falls (12%); 48% pts had ≥2 GS. Nine pts (36%) had impaired 4-meter gait speed and/or timed-up-and-go; 20 pts (80%) had an adjusted CIRS-G score of ≥6. So far, pts have completed a median follow up of 3.3 mos. BARS was the most consistent measure of adherence used (63/63 visits, 100%). MEMS Cap and pill counts were used at 13% and 8% visits respectively. Only 5 pts used the MEMS Cap, mostly due to packaging incompatibility (44%-pill box, 32%-blister packs). Median adherence was 100% (range, 70%-100%) with no pts missing &gt; 7 days of prescribed doses. Five pts (20%) required dose interruptions, mostly due to adverse events. Six pts discontinued therapy and 2 pts died of unrelated causes. Median PFS was not reached. Chronological age and presence of a GS were not associated with adherence rate or outcomes. Conclusions: Despite presence of ≥2 geriatric syndromes in 48% of older adults with NHL on OTT, self-reported adherence remains high ( &gt; 99%) in this group. The MEMS Cap device has poor applicability in measuring adherence to OTT due to pill package incompatibility and increasing use of virtual/tele visits.

P28.01 The Clinical Pharmacist as a Member of a Multidisciplinary Team for Lung Cancer Patients Assistance

The recent finds related to molecular biology have been modifying treatment scenarios for lung cancer patients. Along with better understanding of different genetic changes and signalling pathways, new drugs have been developed for that kind of cancer treatment. Due to broad type of clinic protocols and oncological drug combinations, the participation of clinic pharmacists working as a multiprofessional team member has increased. In this article we will describe the caregiving model developed for patient treatment by a specialized clinical pharmacist. This article aims to provide a real case of a multiprofessional team that have been acting in specialized pharmaceutical patient monitoring. All patients were diagnosed with lung cancer and treated between november of 2018 and July of 2020, in a private oncologic clinic in the city of Rio de Janeiro, Brazil. We developed a pharmacist assistance model for lung cancer patients in order to improve its experience, safety and quality of life during all treatment scope (figure 1). 273 patients and 23 types of different oncological drugs were identified for lung cancer treatment, with 4 different types of pharmaceutical classes: 40% oral target-therapy; 30% conventional chemotherapy; 22% immunotherapy and 8% intravenous target-therapy. All patients were conducted by a previous clinical pharmacist query before begginning of treatment. Were evaluated: degree of treatment understanding of patient and caregiver; distress levels through assessment “thermometer”; identification and registration of allergies; smoking; social habits; comorbidities and drug reconciliation. Each patient received an individualized care plan, education material with guidance for drug administration and packaging of oncological medicines for home use, telephone follow-up to assess adherence and schedule of laboratory tests. Of the patients consulted by the clinical pharmacist, 67% needed pharmaceutical intervention, being referred for assessment of nutrition, psychologist or reassessment by the oncologist. 97% of pharmaceutical interventions were accepted by the multidisciplinary team. All identified drug toxicities were recorded and no patient abandoned treatment. With new oncological drugs for lung cancer treatment available on the market, it has been necessary a better understanding of protocols and monitoring plans for intravenous administration or for oral administration. The clinical pharmacist is a key factor for correct patient monitoring for each different types of protocols, by helping reduce drug interactions risks, toxicity identification and developing better treatment adherence. For this method of assistance to succeed, the presence of the pharmacist is fundamental on the “tumor board” and its inclusion as a member of multidisciplinary team.

Impact of Oral Targeted Therapy on the Economic Burden of Chronic Lymphocytic Leukemia in Canada.

Background: Continuous oral targeted therapy (OTT) for chronic lymphocytic leukemia (CLL) represents an effective therapy but also a major economic burden on the healthcare system. This study aimed to estimate future direct costs, along with the prevalence, of CLL in the era of continuous OTT in Canada. Methods: The economic burden of OTT was modelled and compared to chemoimmunotherapy (CIT), for CLL treatment. The burden was assessed/projected from 2011 to 2025. For the OTT scenario, CIT was considered the standard of care before 2015, while OTT was considered standard of care for patients with either unmutated immunoglobulin heavy-chain variable (IGHV) or del(17p)/TP53 mutations starting in 2015 and, from 2020 onwards, for all first-line treatments except for patients with mutated IGHV. A Markov model was developed including four health states: watchful-waiting, first-line treatment, relapse and death. Costs of therapy, follow-up/monitoring and adverse events were included. Key clinical parameters were extracted from pivotal clinical trials. Results: As incidence rates and rate of survival are increasing, the prevalence of CLL in Canada is projected to increase 1.8-fold, from 8301 patients in 2011 to 14,654 by 2025. Correspondingly, the total annual costs of CLL management are predicted to increase 15.7-fold, from $60.8 million to $957.5 million during that same period. Conclusions: Although OTT enhances survival for patients with CLL, it is nonetheless associated with an important economic burden due to the projected vast increase in costs from 2011 to 2025. Changes in clinical strategies, such as implementation of a fixed OTT treatment duration, could help alleviate financial burden.

LGG-01. CLINICAL MANAGEMENT AND GENOMIC PROFILING OF PEDIATRIC LOW-GRADE GLIOMAS IN SAUDI ARABIA

Pediatric Low Grade Gliomas (PLGGs) display heterogeneity regarding morphology, genomic drivers and clinical outcomes. The treatment modality dictates the outcome and optimizing patient management can be challenging. In this study, we profiled a targeted panel of cancer-related genes in 37 Saudi Arabian patients with pLGGs to identify genetic abnormalities that can inform prognostic and therapeutic decision-making. We detected genetic alterations (GAs) in 97% (36/37) of cases, averaging 2.51 single nucleotide variations (SNVs) and 0.91 gene fusions per patient. The KIAA1549-BRAF fusion was the most common alteration (21/37 patients) followed by AFAP1-NTRK2 (2/37) and TBLXR-PI3KCA (2/37) fusions that were observed at much lower frequencies. The most frequently mutated) genes were NOTCH1 3 (7/37), ATM (4/37), RAD51C (3/37), RNF43 (3/37), SLX4 (3/37) and NF1 (3/37). BRAF V600E mutations were observed in only 2/37 patients, while H3F3A (K27M) histone mutations were not detected. Interestingly, we identified a GOPC-ROS1 fusion in an 8-year-old patient whose tumor lacked BRAF alterations and histologically classified as low grade glioma. The patient underwent gross total resection (GTR) currently he is disease free. To our knowledge this is the first report of GOPC-ROS1 fusion in PLGG which may represent a genomically-distinct subgroup of pLGGs that could be targeted with oral target therapy crizotinib. Taken together, we reveal the genetic characteristics of pLGG Saudi patients can enhance diagnostics and therapeutic decisions. In addition, we identified a GOPC-ROS1 fusion that may be a biomarker for pLGG. Our study proves the possibility of using genetic profiling to guide optimal treatment strategies for pLGG in Saudi population

Identification of factors associated with aggressive end-of-life antitumour treatment: retrospective study of 1282 patients with cancer.

Antitumour treatment in the last 2 weeks of death (ATT-W2) and a new regimen of ATT within 30 days of death (NATT-M1) are considered as aggressive end-of-life (EOL) care. We aimed to assess factors associated with inappropriate use of antitumour treatment (ATT) at EOL. Data of patients with cancer who died in 2013, 2015, 2017 and 2019 in a single for-profit cancer centre were retrospectively analysed. ATT was divided into chemotherapy (CT), oral targeted therapy (OTT), hormonotherapy and immunotherapy (IMT). A total of 1282 patients were included. NATT-M1 was given to 197 (15.37%) patients, and 167 (13.03%) had an ATT-W2. Patients with a performance status of <2 and treated with CT had more both ATT- W2 (OR=2.45, 95% CI 1.65 to 3.65, and OR=10.29, 95% CI 4.70 to 22.6, respectively) and NATT-M1 (OR=2.01, 95% CI 1.40 to 2.90, and OR=8.41, 95% CI 4.46 to 15.86). Predictive factors of a higher rate of ATT-W2 were treatment with OTT (OR=19.08, 95% CI 7.12 to 51.07), follow-up by a medical oncologist (OR=1.49, 95% CI 1.03 to 2.17), miscellaneous cancer (OR=3.50, 95% CI 1.13 to 10.85) and length of hospital stay before death of <13 days (OR=1.92, 95% CI 1.32 to 2.79). Urinary tract and male genital cancers received less ATT-W2 (OR=0.38, 95% CI 0.16 to 0.89, and OR=0.40, 95% CI 0.16 to 0.99) and patients treated by IMT or with age <69 years more NATT-M1 (OR=19.21, 95% CI 7.55 to 48.8, and OR=1.69, 95% CI 1.20 to 2.37). Patients followed up by the palliative care team (PCT) had fewer ATT-W2 and NATT-M1 (OR=0.49, 95% CI 0.35 to 0.71, and OR=0.42, 95% CI 0.30 to 0.58). Most recent ATT and access to a PCT follow-up are the two most important potentially modifiable factors associated with aggressive EOL in patients with cancer. Early integrated palliative oncology care could help to decrease futile ATT at EOL.

Prevalence and predictors of patients reporting adverse drug reactions to health care providers during oral targeted cancer treatment

BackgroundPharmacovigilance is a critical component to facilitate clinicians’ decision-making to alter or discontinue therapy. However, self-administration of oral targeted therapy (OTT) requires fewer clinical visits than parenteral infusions, potentially leading to an increase in the under-reporting of adverse drug reactions (ADRs). Objective(s)To identify factors associated with patients reporting ADRs to their health care provider (HCP) and to identify the prevalence of unreported ADRs while on OTT. MethodsPatients aged ≥18 years who received care from a community oncology clinic and newly prescribed an OTT between August 1, 2018, and October 31, 2018, were included. Six-monthly follow-up calls were conducted by the pharmacy staff to assess for gradable ADRs—validated by the NCI Common Terminology Criteria for Adverse Events—and ungradable ADRs. Descriptive analysis was used to analyze the prevalence of unreporting ADRs, and a multivariate logistic regression model was utilized to evaluate predictors of reporting ADRs to an HCP. Predictors included sociodemographic factors, severity of ADRs, insurance type, pharmacy setting, type of OTT, and the number of prescribed medications ResultsOf the 76 patients analyzed, the mean age was 63.32 ±11.55 years, 84.2% were women, 68.8% were non-Hispanic white, and 76.3% had breast cancer. During the follow-up calls, 306 ADRs were identified and 22.2% were not previously reported to an HCP. Of the unreported gradable ADRs, 63.2% were grade 1, 19.3% were grade 2, and 17.5% were grade 3. We found that for every 1-year increase in age, there was a 5% decrease in the likelihood of reporting ADRs (95% CI, 0.91–0.99), and men were 11.4 times more likely to report ADRs (95% CI, 1.29–100.8). ConclusionFollow-up calls served as an outlet to collect pharmacovigilance data by identifying over 20% of unreported ADRs to HCPs, in which over one-third were moderate to severe. However, future studies are needed to further understand the statistically significant differences found in under-reporting for women and the older population.

1380P Description of the clinical characteristics and survival in patients with metastatic NSCLC in the Spanish population: An analysis of the thoracic tumours registry (RTT study)

The lung cancer is the leading cause of death due to cancer in Western countries, the prognosis depends on the tumor stage and the clinical, histological and molecular characteristics. The RTT study of the Spanish Lung Cancer Group is a database that includes the data of patients with lung malignant neoplasms. The objective of this retrospective study is to descriptive the clinical and epidemiological aspects of NSCLC in the Spanish population. The total of patients included in the RTT is 12.897 (Aug 2016 - Jan 2020) and this report is based in the analysis of 5.049 of them. The clinical and demographic data are described in the table. Adenocarcinoma (72,2%), squamous cell carcinoma (SCC) (18,6%), other types. The sites of metastasis: contralateral lung (34.3%), bone (31%), liver (12.8%) and CNS (6.02%). The first-line of treatment was chemotherapy (CT) in 66,54%, oral target therapy 13,45%, immunotherapy (IO) 8,62% and CT+IO 2,46%. The median of PFS of 7.4 months (7.13-7.6 months) in all population with an estimated at 6, 12, 24, and 60 months of 58.3% (95%CI 56.81% - 59.74%), 29.97% (95%CI 28.56% - 31.4%), 13.4% (95%CI 12.2% - 14.6%) and 2.6% (95%CI 1.98%-3.5%) respectively. The median of OS was 15.5 months (14.8-16.4). According to the histological type (SCC vs non-SCC), the median (in months) of PFS was 6.67 (6.1- 7.1) vs 7.53 (7.3-7.9) (HR 0.78, 95% CI 0.72 - 0.85) and OS 13.8 (12.6-15.6) vs 16.9 (15.7 - 18) in non-SSC, p <0.001. The analysis of survival in patients with or without liver metastasis showed a median OS of 15 months (14.3-16m) vs 18.1 months (16.1- 19.9m), HR 0.88, 95%CI 0.79-0.98 (p<0.05).Table: 1380PN=5049Age, Median68, 29 y (25-96)SexM:71,16% - F:28,83%Smoking habit Smoker Former smoker Never smoker42,42% 41,06% 15,56%Asbestos exposure2,14%Patient history of cancer13,5%Family history of cancer40,82% Open table in a new tab The results of our study show a similarity in the clinical characteristics of patients with NSCLC in the Spanish population with the data in the western population previously described. Both, the histological subtype and the presence of liver metastases are predictive factors for survival.