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Objective Oral tyrosine kinase inhibitors (TKIs) are first line therapy for chronic myeloid leukemia (CML). A complete cytogenetic response (CCyR) correlates with increased overall survival, however only 66%–88% of patients achieve CCyR after one year of TKI treatment. Because TKI therapy alone cannot eliminate CML stem cells, strategies aimed at achieving faster and deeper responses are needed to improve long-term survival. Metformin is a widely prescribed glucose-lowering agent for patients with diabetes and in preclinical studies, has been shown to suppress cell viability, induce apoptosis, and downregulate the mTORC1 signaling pathway in imatinib resistant CML cell lines (K562R). This study aims to investigate the utility of metformin added to TKI therapy in patients with CML. Data Sources An observational study at an academic medical center (Salt Lake City, UT) was performed for adults with newly diagnosed, chronic-phase CML to evaluate attainment of CCyR from TKI therapy with or without concomitant metformin use. Descriptive analyses were used to describe baseline characteristics and attainment of response to TKI therapy. Data Summary Fifty-nine patients were evaluated. One hundred percent (5 of 5) in the metformin group and 73.6% (39 of 54) in the non-metformin group achieved CCyR. Approximately 20% of patients in both groups relapsed (defined by a loss of CCyR during study) after a median 34.5 months of follow-up. Conclusions Future research is warranted to validate these findings and determine the utility of metformin added to TKI therapy.

Background Glioblastoma is an incurable disease with a poor prognosis. For caregivers of people with glioblastoma, the burden of care can be high. Patients often present with different clinical characteristics, which may impact caregiver burden in different ways. This study aimed to evaluate associations between patient clinical characteristics and caregiver burden/quality of life (QoL). Methods Caregiver–patient dyads were enrolled at 7 academic cancer centers in the United States. Eligible caregiver participants were self-reported as the primary caregiver of an adult living with glioblastoma and completed a caregiver burden survey. Eligible patients were age ≥ 18 years at glioblastoma diagnosis and alive when their respective caregiver entered the study, with the presence of cognitive dysfunction confirmed by the caregiver. Data were analyzed with descriptive statistics and multivariable analyses. Results The final cohort included 167 dyads. Poor patient performance status resulted in patient difficulty with mental tasks, more caregiving tasks, and increased caregiving time. Language problems were reported in patients with left-sided lesions. Patient confusion was negatively associated with all caregiver domains: emotional health, social health, general health, ability to work, confidence in finances, and overall QoL. Better caregiver QoL was observed in patients with frontal lobe lesions versus non-frontal lobe lesions. Conclusion This study reinforced that patient performance status is a critical clinical factor that significantly affects caregiver burden, caregiving tasks, and caregiver time. Additionally, patient confusion affects multiple facets of caregiver burden/QoL. These results could be used to support guided intervention for caregiver support, customized to the patient experience.

Since the publication of the Human Genome Project, genetic information has been used as an accepted, evidence‐based biomarker to optimize patient care through the delivery of precision health. Pharmacogenetics (PGx) uses information about genes that encode proteins involved in pharmacokinetics, pharmacodynamics, and hypersensitivity reactions to guide clinical decision making to optimize medication therapy selection. Clinical PGx implementation is growing from the dramatic increase in PGx studies over the last decade. However, an overwhelming lack of genetic diversity in current PGx studies is evident. This lack of diverse representation in PGx studies will impede equitable clinical implementation through potentially inappropriate application of gene‐based dosing algorithms, whereas representing a missed opportunity for identification of population specific single nucleotide variants and alleles. In this review, we discuss the challenges of studying PGx in under‐represented populations, highlight two successful PGx studies conducted in non‐European populations, and propose a path forward through community‐based participatory research for equitable PGx research and clinical translation.

Several healthcare organizations across Minnesota have developed formal pharmacogenomic (PGx) clinical programs to increase drug safety and effectiveness. Healthcare professional and student education is strong and there are multiple opportunities in the state for learners to gain workforce skills and develop advanced competency in PGx. Implementation planning is occurring at several organizations and others have incorporated structured utilization of PGx into routine workflows. Laboratory-based and translational PGx research in Minnesota has driven important discoveries in several therapeutic areas. This article reviews the state of PGx activities in Minnesota including educational programs, research, national consortia involvement, technology, clinical implementation and utilization and reimbursement, and outlines the challenges and opportunities in equitable implementation of these advances.

Background First-line (1L) immunotherapy (I-O) has improved outcomes in patients with advanced non-small cell lung cancer (NSCLC) in clinical trials and is now routinely used alone or combined with chemotherapy. Although efficacy and safety of I-O therapies have been established in clinical trials, little is known about their performance and long-term efficacy in the real-world setting. We aimed to characterize real-world outcomes for patients with advanced NSCLC treated with 1L I-O therapy in the United States. Methods Patients aged ≥18 years with confirmed advanced (stage III–IV) NSCLC who received either 1L I-O monotherapy or single-agent I-O combined with chemotherapy on or after January 1, 2016 were identified from the Flatiron Health database. Primary objectives were to examine overall survival (OS) and real-world progression-free survival. Index date was defined as date of 1L treatment initiation; data cut-off date was June 30, 2020. Results Among 4271 patients receiving I-O plus chemotherapy, median OS was 10.6 (95 % confidence interval [CI], 9.3–11.8) months in patients with squamous NSCLC (n=814) and 12.0 (95 % CI, 11.3–12.8) months in those with non-squamous disease (n=3457). Regardless of histology, patients with high (≥50 %) tumor programmed death ligand 1 (PD-L1) expression demonstrated longer median OS vs those with low expression. Among 3041 patients receiving I-O monotherapy, median OS was 11.3 (95 % CI, 9.8–12.8) months in patients with squamous NSCLC (n=875) and 14.1 (95 % CI, 12.4–15.8) months in those with non-squamous disease (n=2166). OS benefit appeared to be greatest in the ≥50 % tumor PD-L1 expression group of the non-squamous cohort. Conclusion Survival estimates were generally lower than those reported in pivotal clinical trials. These findings indicate that there remains room for improvement of real-world survival outcomes in patients with advanced NSCLC who receive 1L I-O–based regimens and for identification of subgroups of patients not benefitting from treatment with current I-O regimens.

Background: Venous thromboembolism (VTE) is a common complication among patients with cancer. Patients with cancer and VTE are at a markedly increased risk for morbidity and mortality. Objective: These evidence-based guidelines of the American Society of Hematology (ASH) are intended to support patients, clinicians, and other health care professionals in their decisions about the prevention and treatment of VTE in patients with cancer. Methods: ASH formed a multidisciplinary guideline panel balanced to minimize potential bias from conflicts of interest. The guideline development process was supported by updated or new systematic evidence reviews. The Grading of Recommendations Assessment, Development, and Evaluation (GRADE) approach was used to assess evidence and make recommendations. Results: Recommendations address mechanical and pharmacological prophylaxis in hospitalized medical patients with cancer, those undergoing a surgical procedure, and ambulatory patients receiving cancer chemotherapy. The recommendations also address the use of anticoagulation for the initial, short-term, and long-term treatment of VTE in patients with cancer. Conclusions: Strong recommendations include not using thromboprophylaxis in ambulatory patients receiving cancer chemotherapy at low risk of VTE and to use low-molecular-weight heparin (LMWH) for initial treatment of VTE in patients with cancer. Conditional recommendations include using thromboprophylaxis in hospitalized medical patients with cancer, LMWH or fondaparinux for surgical patients with cancer, LMWH or direct oral anticoagulants (DOAC) in ambulatory patients with cancer receiving systemic therapy at high risk of VTE and LMWH or DOAC for initial treatment of VTE, DOAC for the short-term treatment of VTE, and LMWH or DOAC for the long-term treatment of VTE in patients with cancer.

696 Background: PERT is an important but costly and inconsistently used supportive care medication in PC. We sought to characterize patterns of PERT use among U.S. insured patients with PC. Methods: We conducted a retrospective observational analysis of patients with a primary diagnosis of pancreatic adenocarcinoma in the IBM MarketScan national claims database between 2013-2019. We identified pharmacy claims for PERT (Creon, Pancreaze, Pertzye, Viokace, and Zenpep) and classified patients as PERT-users (≥ 1 PERT prescription [Rx]) and non-PERT users. We used descriptive statistics for clinical, demographics, and costs. Multiple logistic regression identified predictors of PERT use. Kaplan-Meier method assessed time from PC diagnosis to first PERT Rx. Results: Of 19,866 patients with PC (median age 62 years, 49% women), 6,918 (35%) were PERT-users. The median follow-up was 11 months (PERT users: 14 months, non-PERT users: 9 months). Overall, 43% of patients received no cancer-directed treatment. PERT-users were more likely to have a history of pancreatitis (acute, odds ratio [OR] = 1.9; chronic, OR = 3.6), and received chemotherapy (OR = 1.2), surgery (OR = 2.3), and radiation (OR = 1.4). Among all PERT-users, the median time from PC diagnosis to first fill was 1.9 months (95% CI: 1.8,2.0). The median time from surgery to first fill was 1.6 months (95% CI: 1.4,1.7). The median number of PERT Rxs was 4; 22% of PERT-users received 1 Rx. A median of 150 days of PERT was supplied across all Rxs per patient. The median (IQR) cost of each PERT Rx was $25 ($0- $50). PERT accounted for 16% of all drug out-of-pocket costs (OOPC) (excluding systemic outpatient cancer-directed treatment), and 7% of all healthcare OOPC. Patients with PERT had significantly higher monthly OOPC on Rxs but lower on all other services, including inpatient and outpatient services (all p < 0.0001). Overall, PERT-users had significantly lower per-patient per-month (PPPM) OOPC vs non-PERT users ($469, vs $520, p < 0.0001). They also had fewer PPPM outpatient (0.7 vs 1.2, p < 0.0001) and ER (0.4 vs 0.5, p < 0.0001) visits. Conclusions: In this national study of insured U.S. adults with PC, only one-third received PERT. Of those receiving PERT, approximately a fifth received just a single Rx. PERT users, despite higher OOP drug spending had reduced overall OOP costs and fewer healthcare visits. These data highlight the need to explore non cost-related reasons for lack of and ways to standardize PERT use.

Germline BRCA mutations (BRCAm) strongly influence the risk of developing breast cancer. This study aimed to understand the role of BRCAm testing in affected individuals and to assess its impact on the outcome of BRCAm carriers compared to non-carriers (BRCAwt) with breast cancer. The research question is “Does standard of care testing for BRCAm improve survival outcomes of breast cancer patients?” In a single institution observational cohort study, demographic and clinical characteristics were compared between breast cancer patients with and without BRCAm. Frequency of BRCA testing was assessed. Survival outcomes were assessed by initial treatment setting stratified by BRCA status. Of 5712 identified women with breast cancer, 14.6% (n = 835) were tested for a BRCA mutation and had a documented result. The total number and proportion of women tested for a BRCAm increased between 2000 and 2014, resulting in an increased number of BRCAm carriers identified. However, the proportion of women who underwent testing and had a BRCAm decreased during the study period from 27.5% in 2000–2004 to 13.3% in 2010–2014. Disease-free survival was similar in the adjuvant and neoadjuvant treatment settings between BRCAm and BRCAwt patients. Progression-free survival on first line treatment and overall survival for patients with metastatic disease was also similar between BRCAm and BRCAwt patients. The proportion of women tested and the number of BRCAm identified increased during the study period despite a decreasing proportion of positive results among women tested.

The extent to which immune cell phenotypes in the peripheral blood reflect within-tumor immune activity prior to and early in cancer therapy is unclear. To address this question, we studied the population dynamics of tumor and immune cells, and immune phenotypic changes, using clinical tumor and immune cell measurements and single-cell genomic analyses. These samples were serially obtained from a cohort of advanced gastrointestinal cancer patients enrolled in a trial with chemotherapy and immunotherapy. Using an ecological population model, fitted to clinical tumor burden and immune cell abundance data from each patient, we find evidence of a strong tumor-circulating immune cell interaction in responder patients but not in those patients that progress on treatment. Upon initiation of therapy, immune cell abundance increased rapidly in responsive patients, and once the peak level is reached tumor burden decreases, similar to models of predator–prey interactions; these dynamic patterns were absent in nonresponder patients. To interrogate phenotype dynamics of circulating immune cells, we performed single-cell RNA sequencing at serial time points during treatment. These data show that peripheral immune cell phenotypes were linked to the increased strength of patients’ tumor–immune cell interaction, including increased cytotoxic differentiation and strong activation of interferon signaling in peripheral T cells in responder patients. Joint modeling of clinical and genomic data highlights the interactions between tumor and immune cell populations and reveals how variation in patient responsiveness can be explained by differences in peripheral immune cell signaling and differentiation soon after the initiation of immunotherapy.

// Connor Willis 1 , Michelle Fiander 1 , Dao Tran 2 , Beata Korytowsky 3 , John-Michael Thomas 3 , Florencio Calderon 3 , Teresa M. Zyczynski 3 , Diana Brixner 1 and David D. Stenehjem 1 , 2 1 Department of Pharmacotherapy, University of Utah, Salt Lake City, UT, USA 2 Department of Pharmacy Practice and Pharmaceutical Sciences, University of Minnesota, Duluth, MN, USA 3 Bristol-Myers Squibb Company, Lawrenceville, NJ, USA Correspondence to: David Stenehjem, email: stene032@d.umn.edu Keywords: biomarkers; chemotherapy; immunotherapy; lung cancer; PD-L1 Received: June 14, 2019 Accepted: September 16, 2019 Published: November 12, 2019 ABSTRACT Purpose: To assess the association of tumor mutational burden (TMB) with clinical outcomes, other biomarkers and patient/disease characteristics in patients receiving therapy for lung cancer. Results: In total, 4,303 publications were identified; 81 publications were included. The majority of publications assessing clinical efficacy of immunotherapy reported an association with high TMB, particularly when assessing progression-free survival and objective response rate. High TMB was consistently associated with TP53 alterations, and negatively associated with EGFR mutations. High TMB was also associated with smoking, squamous cell non-small cell lung carcinoma, and being male. Methods: A systematic literature review based upon an a priori protocol was conducted following Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) and Cochrane methodologies. Searches were conducted in EMBASE, SCOPUS, Ovid MEDLINE ® , and Emcare (from January 2012 until April 2018) and in two clinical trial registries. Conference abstracts were identified in EMBASE, and in targeted searches of recent major conference proceedings (from January 2016 until April 2018). Publications reporting data in patients receiving therapy for lung cancer that reported TMB and its association with clinical efficacy, or with other biomarkers or patient/disease characteristics, were included. Results are presented descriptively. Conclusion: This systematic literature review identified several clinical outcomes, biomarkers, and patient/disease characteristics associated with high TMB, and highlights the need for standardized definitions and testing practices. Further studies using standardized methodology are required to inform treatment decisions.

While results from clinical trials are important in determining the efficacy of treatment, restrictive eligibility criteria may limit generalizability to patient populations in the real-world setting. Real-world analyses can therefore identify subgroups of patients who may respond differently to specific therapeutic regimens. This supplementary data is supportive to the research article entitled “Real-world outcomes of immunotherapy–based regimens in first-line advanced non-small cell lung cancer” [1] . Using electronic health records data from a large demographically and geographically diverse oncology database, we present real-world progression-free survival (rwPFS) outcomes for patients with advanced non-small cell lung cancer in the United States treated with either first-line immunotherapy as monotherapy or single-agent immunotherapy combined with chemotherapy. rwPFS was estimated for patients in each treatment group using Kaplan-Meier methods; analyses were conducted separately for patients with squamous and non-squamous histology and stratified by Eastern Cooperative Oncology Group performance status, tumor programmed death ligand-1 expression, and presence of brain metastases.

Glioblastoma is an incurable disease with a poor prognosis. For caregivers of people with glioblastoma, the burden of care can be high. Patients often present with different clinical characteristics, which may impact caregiver burden in different ways. This study aimed to evaluate associations between patient clinical characteristics and caregiver burden/quality of life (QoL).Caregiver-patient dyads were enrolled at 7 academic cancer centers in the United States. Eligible caregiver participants were self-reported as the primary caregiver of an adult living with glioblastoma and completed a caregiver burden survey. Eligible patients were age ≥ 18 years at glioblastoma diagnosis and alive when their respective caregiver entered the study, with the presence of cognitive dysfunction confirmed by the caregiver. Data were analyzed with descriptive statistics and multivariable analyses.The final cohort included 167 dyads. Poor patient performance status resulted in patient difficulty with mental tasks, more caregiving tasks, and increased caregiving time. Language problems were reported in patients with left-sided lesions. Patient confusion was negatively associated with all caregiver domains: emotional health, social health, general health, ability to work, confidence in finances, and overall QoL. Better caregiver QoL was observed in patients with frontal lobe lesions versus non-frontal lobe lesions.This study reinforced that patient performance status is a critical clinical factor that significantly affects caregiver burden, caregiving tasks, and caregiver time. Additionally, patient confusion affects multiple facets of caregiver burden/QoL. These results could be used to support guided intervention for caregiver support, customized to the patient experience.

11523 Background: Desmoid tumors are known to have increased nuclear β-catenin levels. Tegavivint selectively disrupts the interaction of β-catenin and TBL1/ TBLR1, resulting in specific degradation of nuclear β-catenin. The primary objectives of this study were to determine the maximum tolerated dose (MTD), safety, and preliminary efficacy of tegavivint in patients (pts) with desmoid tumors. Methods: This study ( NCT03459469) utilized an accelerated dose escalation schema for the first two dose levels followed by a 3+3 design to determine the MTD/recommended phase 2 dose (RP2D) of tegavivint, followed by a dose expansion phase. The study included adult pts with sporadic desmoid tumors that were progressive (20% increase in tumor volume, recurrent in one year from surgery, or symptomatic), unresectable, and measurable via WHO criteria. Tegavivint was administered IV weekly (three weeks on, one week off) up to two years. Results: 24 pts were enrolled. Dose escalation enrolled 17 pts in six dose levels from 0.5 - 5 mg/kg. In dose expansion, 7 additional pts were enrolled. Dose expansion cohort also included 6 pts in dose escalation that were escalated to RP2D and 3 pts treated at RP2D in dose escalation (n = 16 total). Median age was 43 years (18-66). Median time from diagnosis was 3.1 years with median of one prior systemic treatment (range 0-6). Median time on study was 9.4 months; 3 pts remain on study at data cut-off. No dose-limiting toxicities were observed; MTD was not determined. RP2D was declared at 5 mg/kg based on pharmacologically relevant plasma concentrations and preliminary efficacy. Trough plasma concentrations (Cmin) exceeded in vitro IC50 efficacy estimates at 4 mg/kg and 5 mg/kg. Median half-life was 38 hours supporting once weekly administration. Treatment-related adverse events (TRAEs) occurring in ≥20% of pts included fatigue (71%), headache (38%), nausea (33%), constipation (21%), decreased appetite (21%), and dysgeusia (21%), mostly Grade 1-2. Grade 3 TRAEs of hypophosphatemia, stomatitis, increased ALT, diarrhea, and headache occurred in 5 separate pts. There were no grade 4-5 adverse events (AEs). One serious AE of Grade 2 extravasation occurred. Objective response rate (ORR) of 17% across all dose levels and 25% at RP2D (WHO and RECIST criteria) were observed. Median duration of response was 8.1 months (range 6 to 11.8 months) with all responses ongoing. The 9-month progression free survival rate was 76% (95% CI: 54 - 90%) among all pts and 79% (95% CI: 51 – 93%) among those treated at RP2D. Patient reported outcomes and correlative science will be included in the presentation. Conclusions: Tegavivint is well tolerated with mostly Grade 1/2 AEs and no serious toxicity associated with WNT inhibition. The ORR of 25% at the RP2D warrants continued development of tegavivint in desmoid tumors. Clinical trial information: NCT03459469.

e18523 Background: Many patients with cancer (PwC) possess a suboptimal understanding of their chemotherapy treatment plan.1 Accordingly, PwC may seek information regarding both the disease and its treatment from other resources. Purpose: A freely-accessible website was curated by oncology pharmacists to provide evidence-based educational material on chemotherapy treatment plans. Objective: To use the website to deploy an online survey assessing other modes of education routinely accessed by PwC. Methods: Between February 2020 and January 2021, PwC completed an anonymous, English language survey via www.chemoexperts.com. Results: A total of 1,036 self-identified patient users began the survey. The majority were from North America (75%). Most respondents (65%) were female. PwC were asked: “If you received education from a health care professional (HCP), what type of education did you receive?” Multiple responses were allowed. Of the 820 patients who responded to this question, 77.4% (n = 635) were given printed material, 52.3% (n = 429) were taught in clinic, 8% (n = 66) were shown videos, 5.7% (n = 47) participated in an educational class outside of clinic, and 4% (n = 33) were given magazines. Roughly 37% were directed to an internet site (n = 304; 92 to chemoexperts.com, 212 to other internet sites) by a HCP. Patients also reported using blogs (12.7%; n = 111/873 respondents), websites other than chemoexperts (85%; n = 742/873), support groups (28.4%; n = 248/873), and YouTube (15.1%; n = 132/873). Discussion: In-person teaching sessions are vital to understanding treatment plans. While the ongoing COVID-19 pandemic may have lowered the percentage of PwC who are offered teaching, some PwC may still not absorb or retain all there is to know during in-person sessions and seek other resources to bolster their understanding of treatment. Although the majority of users reported receiving printed material, this too may be limited in its ability to meet the needs of all individuals. Knowing PwC may seek varying modes of education, HCPs should direct patients to resources they are familiar with. Conclusions: To our knowledge, this is the first global survey to examine modes of education utilized by PwC. Although PwC may receive teaching in person, many still seek a variety of educational resources outside of clinic. Relying solely on printed material will not meet the needs of some PwC. When educating PwC in clinic, HCPs concerned about the validity of outside materials should direct patients to resources they are familiar with and trust. Reference: Almalki H, Absi A, Alghamdi A, Alsalmi M, Khan M. Analysis of Patient-Physician Concordance in the Understanding of Chemotherapy Treatment Plans Among Patients With Cancer. JAMA Netw Open. 2020 Mar 2;3(3):e200341.

Objective To examine the comparative efficacy and safety of interventions for preventing chemotherapy-induced oral mucositis (OM) in adult cancer patients. Methods We searched PubMed, Embase and the Cochrane Central systematically for the randomised control trials (RCTs) of interventions for preventing OM. Network meta-analysis (NMA) was performed to estimate risk ratios (RR) and 95% confidence intervals (CI) from both direct and indirect evidence. The primary outcome was any grade of OM. Secondary outcomes were mild-moderate OM, severe OM and adverse events, such as taste disturbance and gastrointestinal adverse events. This study was registered with PROSPERO, number CRD42016052489. Results A total of 29 RCTs with 2348 patients (median age, 56.1 years; 57.5% male) were included. Cryotherapy was associated with a significantly lower risk of OM than control (RR 0.51, 95% CI 0.38 to 0.68), and zinc sulphate (RR 0.47, 95% CI 0.23 to 0.97), but not significantly lower than sucralfate and palifermin. No significant differences were observed between cryotherapy and control for taste disturbance and gastrointestinal adverse events. Palifermin was associated with the highest risk of taste disturbance. Conclusions This NMA suggests that cryotherapy was the most effective intervention for preventing chemotherapy-induced OM with a safety profile similar to control, but not significantly lower than sucralfate and palifermin. Large RCTs are needed to confirm these findings.

Background: Chemotherapy (CT) alone was previously standard first-line (1L) therapy for metastatic non-small-cell lung cancer (NSCLC) but alternative treatments, including immunotherapy (I-O), are now available. Patients & methods: In this retrospective study, adults with stage IV NSCLC who initiated 1L treatment between 1 August 2018 and 31 December 2019 and had ≥2 visits were identified in the Flatiron database. Patients were followed up until 30 June 2020. Baseline characteristics and treatment patterns were described by treatment group: CT, I-O + CT, I-O monotherapy and other. Results: Approximately 20% of patients received 1L CT in the 2018–2019 timeframe studied; these patients tended to have squamous histology and low (≤49%) programmed death ligand-1 expression. Conclusion: A proportion of patients with metastatic NSCLC still receive 1L CT despite the availability and widespread use of I-O therapies.

Germline BRCA mutations (BRCAm) strongly influence the risk of developing breast cancer. This study aimed to understand the role of BRCAm testing in affected individuals and to assess its impact on the outcome of BRCAm carriers compared to non-carriers (BRCAwt) with breast cancer.The research question is "Does standard of care testing for BRCAm improve survival outcomes of breast cancer patients?"In a single institution observational cohort study, demographic and clinical characteristics were compared between breast cancer patients with and without BRCAm. Frequency of BRCA testing was assessed. Survival outcomes were assessed by initial treatment setting stratified by BRCA status.Of 5712 identified women with breast cancer, 14.6% (n = 835) were tested for a BRCA mutation and had a documented result. The total number and proportion of women tested for a BRCAm increased between 2000 and 2014, resulting in an increased number of BRCAm carriers identified. However, the proportion of women who underwent testing and had a BRCAm decreased during the study period from 27.5% in 2000-2004 to 13.3% in 2010-2014. Disease-free survival was similar in the adjuvant and neoadjuvant treatment settings between BRCAm and BRCAwt patients. Progression-free survival on first line treatment and overall survival for patients with metastatic disease was also similar between BRCAm and BRCAwt patients.The proportion of women tested and the number of BRCAm identified increased during the study period despite a decreasing proportion of positive results among women tested.

Background Breast cancer costs were estimated at $16.5 billion in 2010 and were higher than other cancer costs. There are limited studies on breast cancer charges and costs by BRCA mutations and receptor status. We examined overall health care and breast cancer-related charges by BRCA status (BRCAm vs. BRCAwt), receptor status (HER2+ vs. HER2-), and treatment setting (neoadjuvant vs. adjuvant). Methods Retrospective cohort study of charge data from 1995-2014 in an academic medical center. Facilities, physician, pharmacy, and diagnosis-related charges were presented as mean and median charges with standard deviation (SD) and interquartile ranges (25%-75%). Wilcoxon rank-sum test was used to assess statistically significant differences in charges between comparators. Results Total median breast-cancer related charges were $65,414 for BRCAm and $54,635 for BRCAwt (p=0.19); however all-cause charges were higher for BRCAm patients ($145,066 vs. $119,119, ppp Conclusion BRCA mutation status was not associated with higher breast cancer charges but HER2+ status had significantly higher charges, due to charges for biological agents. Patients who initially received neoadjuvant treatment had significantly higher overall treatment charges than adjuvant therapy patients. With the advent of novel therapies for BRCAm, the economic impact of these treatments will be important to consider relative to their survival benefits.

The extent that immune cell phenotypes in the peripheral blood reflect within-tumor immune activity prior to and early in cancer therapy is unclear. To address this question, we studied the population dynamics of tumor and immune cells, and immune phenotypic changes, using clinical tumor and immune cell measurements and single cell genomic analyses. These samples were serially obtained from a cohort of advanced gastrointestinal cancer patients enrolled on a trial with chemotherapy and immunotherapy. Using an ecological population model, fitted to clinical tumor burden and immune cell abundance data from each patient, we find evidence of a strong tumor-circulating immune cell interaction in responder patients, but not those patients that progress on treatment. Upon initiation of therapy, immune cell abundance increased rapidly in responsive patients, and once the peak level is reached, tumor burden decreases, similar to models of predator-prey interactions; these dynamic patterns were absent in non-responder patients. To interrogate phenotype dynamics of circulating immune cells, we performed single cell RNA sequencing at serial time points during treatment. These data show that peripheral immune cell phenotypes were linked to the increased strength of patients’ tumor-immune cell interaction, including increased cytotoxic differentiation and strong activation of interferon signaling in peripheral T-cells in responder patients. Joint modeling of clinical and genomic data highlights the interactions between tumor and immune cell populations and reveals how variation in patient responsiveness can be explained by differences in peripheral immune cell signaling and differentiation soon after the initiation of immunotherapy.One sentence summaryPeripheral immune cell differentiation and signaling, upon initiation of immunotherapy, reflects tumor attacking ability and patient response.Significance statementThe evolution of peripheral immune cell abundance and signaling over time, as well as how these immune cells interact with the tumor, may impact a cancer patient’s response to therapy. By developing an ecological population model, we provide evidence of a dynamic predator-prey like relationship between circulating immune cell abundance and tumor size in patients that respond to immunotherapy. This relationship is not found either in patients that are non-responsive to immunotherapy or during chemotherapy. Single cell RNA-sequencing (scRNAseq) of serial peripheral blood samples from patients show that the strength of tumor-immune cell interactions is reflected in T-cells interferon activation and differentiation early in treatment. Thus, circulating immune cell dynamics reflect a tumor’s response to immunotherapy.

Background: Inherited genetic variants can modify the cancer-chemopreventive effect of aspirin. We evaluated the clinical and economic value of genotype-guided aspirin use for colorectal cancer chemoprevention in average-risk individuals. Methods: A decision analytical model compared genotype-guided aspirin use versus no genetic testing, no aspirin. The model simulated 100,000 adults ≥50 years of age with average colorectal cancer and cardiovascular disease risk. Low-dose aspirin daily starting at age 50 years was recommended only for those with a genetic test result indicating a greater reduction in colorectal cancer risk with aspirin use. The primary outcomes were quality-adjusted life-years (QALY), costs, and incremental cost-effectiveness ratio (ICER). Results: The mean cost of using genotype-guided aspirin was $187,109 with 19.922 mean QALYs compared with $186,464 with 19.912 QALYs for no genetic testing, no aspirin. Genotype-guided aspirin yielded an ICER of $66,243 per QALY gained, and was cost-effective in 58% of simulations at the $100,000 willingness-to-pay threshold. Genotype-guided aspirin was associated with 1,461 fewer polyps developed, 510 fewer colorectal cancer cases, and 181 fewer colorectal cancer-related deaths. This strategy prevented 1,078 myocardial infarctions with 1,430 gastrointestinal bleeding events, and 323 intracranial hemorrhage cases compared with no genetic testing, no aspirin. Conclusions: Genotype-guided aspirin use for colorectal cancer chemoprevention may offer a cost-effective approach for the future management of average-risk individuals. Impact: A genotype-guided aspirin strategy may prevent colorectal cancer, colorectal cancer-related deaths, and myocardial infarctions, while minimizing bleeding adverse events. This model establishes a framework for genetically-guided aspirin use for targeted chemoprevention of colorectal cancer with application toward commercial testing in this population.

Background This phase I/II trial evaluated toxicity and antitumor activity of everolimus plus mFOLFOX6 + bevacizumab for first-line treatment of metastatic colorectal cancer (mCRC). Methods A phase I, modified 3 + 3 Fibonacci schema determined the maximum tolerated dose (MTD) of everolimus, followed by phase II dose expansion. The phase II primary objective was progression-free survival at 6 months (PFS-6 m). Results The everolimus MTD was 10 mg daily with mFOLFOX6 + bevacizumab based on safety from phase I (n = 22). Twenty-five patients were treated in the phase II at 10 mg everolimus daily. Frequent grade 3-4 adverse events were neutropenia (64%), leukopenia (28%) and hypokalemia (26%). Grade 2 stomatitis was observed in 62% of patients. Two dose-limiting toxicities were observed with one attributed to everolimus 10 mg daily (grade 3 diarrhea, hypokalemia, and anorexia) and grade 3 coronary vasospasm attributed to fluorouracil. The objective response rate was 53% and was higher (86%) in those with PTEN deficiency. PFS-6 m was 96% (95% CI 89-99.9%) at the MTD (n = 35). The everolimus recommended phase II dose of this regimen is 7.5 mg daily due to frequent stomatitis and dose reductions. Conclusions Everolimus plus mFOLFOX-6 + bevacizumab is tolerable and demonstrated preliminary efficacy for first-line mCRC. Further studies are warranted in PTEN deficiency.

Background: Tumors with deficient mismatch repair (dMMR) have a favorable immunological phenotype permitting exploitation by immunotherapies. We aimed to assess our institutional experience of dMMR advanced gastrointestinal (GI) cancers treated with the PD-1 inhibitor pembrolizumab. Materials and Methods: We conducted an observational cohort study of a clinical series of patients with dMMR metastatic GI cancers treated with pembrolizumab from 2015 to 2017. Patients were assessed for best response, time to and reason for discontinuation, and adverse events. Results: A total of 13 patients received at least one dose of pembrolizumab. Median age was 62 years (range 33–74 years). Diagnoses included colorectal (colorectal cancer [CRC], n = 7); extrahepatic and intrahepatic cholangiocarcinoma (EHCC,n = 2;n = 1); pancreatic (pancreatic ductal adenocarcinoma [PDAC], n = 2); and adenocarcinoma of the appendix (n = 1). Five patients received concurrent chemotherapy (FOLFOX or capecitabine) with pembrolizumab (200 mg intravenous [IV] q 2 weeks with FOLFOX or 2 mg/kg IV q 3 weeks with capecitabine). Pembrolizumab was administered 2 mg/kg IV q 3 weeks to all patients who received single-agent treatment. Eleven patients were evaluable for response assessment. Three patients had a complete response (CRC and two EHCC) and one of these patients received concomitant pembrolizumab and FOLFOX. Two patients had a partial response, one with PDAC (−88% per RECIST, continues on treatment after 15.7 months) and the other with CRC (−45% per RECIST, continues after 14.6 months), both patients received concomitant pembrolizumab and FOLFOX and are now maintained on single-agent pembrolizumab. The objective response rate was 42%. Three patients experienced immune-related adverse events requiring discontinuation. Conclusions: This single-institution case series confirms the activity of pembrolizumab in various GI cancers harboring dMMR. Future studies are warranted to determine the role of combinatorial treatment with chemotherapy and/or novel immunotherapies in this population.

BACKGROUND GBM is an aggressive cancer with poor prognosis. We explored impact of disease on caregivers by characterizing caregiver burden and QOL associated with patient characteristics. METHODS Primary caregivers of living adult GBM patients with cognitive dysfunction completed a GBM-specific caregiver burden survey and the validated Caregiver Quality of Life Index–Cancer Scale (CQOLC). Patient data were abstracted from medical records (7/2018-4/2019). Patient characteristics were compared between highest and lowest tertile of CQOLC scores (range 0–140); higher scores suggest better QOL. RESULTS There were 140 patient-caregiver dyads enrolled in the study. Mean patient age was 57 years (range 24–63); majority white males (62.9%), unifocal lesion (90%) and normal activity level at diagnosis. Forty-percent had methylated MGMT promoter status. Caregivers were mostly white (61.4%), college-educated female spouses of similar age; 87.8% were caregiving for >6 months. Median CQOLC score was 82 (tertiles: < 76 and >92). More caregivers in the lowest vs highest CQOLC tertile reported ‘not employed due to caregiving’ (52.4% vs 12%, P< 0.01), ‘changes in patients’ personality’ (73.3% vs 42.6%, P< 0.01), ‘patient memory problems’ (93.5% vs 77.1%, P=0.02), and caring for patient with recurrence treated with ‘chemotherapy other than temozolomide’ ([TMZ], 27.7% vs 8.3%, P=0.01). There was > 10% difference in proportion of caregivers in the lowest vs highest CQOLC tertile for the following patient characteristics: largest lesion in right temporal lobe at baseline and partial resection at initial treatment. Conversely, there was > 10% difference in the highest vs lowest CQOLC tertile for Karnofsky score (> 80), largest lesion in right frontal lobe at baseline, surgical clean margins, TMZ for initial treatment, and surgery for recurrence. CONCLUSION Unemployment, patient personality/memory changes, and chemotherapy other than TMZ use had significant impact on caregiver burden/QoL. This may help identify caregivers to receive support and intervention.

Available descriptive statistics for patients with metastatic basal cell carcinoma (mBCC) are limited. To describe disease characteristics, treatment patterns, survival outcomes, and prognostic factors of patients with mBCC, we conducted a retrospective review of electronic health records in the Department of Veterans Affairs (VA). The primary outcome was survival. Data were also collected on demographics, comorbidities, medications, and procedures. Median (IQR) age of patients with mBCC (n = 475) was 72.0 (17.0) years; 97.9% of patients were male. Almost two-thirds of patients received no initial therapy for mBCC. Median overall survival was 40.5 months [95% CI (confidence interval) 4.8-140.0], and was shorter in patients with distant metastases (17.1 months; 95% CI 2.8-58.0) than in those with regional metastases (59.4 months; 95% CI 17.6-140.0). Because the VA mBCC population is largely male and elderly, the generalizability of these results in other populations is limited and must be interpreted cautiously. Data from this large cohort add valuable information on a rare and poorly researched disease and refine previously wide estimates of overall survival for mBCC.

Romiplostim is a thrombopoietin receptor agonist approved for the treatment of immune thrombocytopenia purpura. When following FDA-approved romiplostim prescribing recommendations to withhold treatment for platelet counts above 400k/µL, some patients exhibit a precipitous decline in their platelet count potentially causing patient harm. We present two cases where stable platelet counts were achieved only through persistent weekly dosing of romiplostim despite platelet counts above 400k/µL on the day of administration. Therefore, continuous weekly dosing of romiplostim despite platelet count being above 400k/µL combined with twice weekly vigilant monitoring is an alternative method of romiplostim dosing that mitigates severe fluctuations in platelets. We also discuss important details, postulated mechanisms, and evidence-based mitigation strategies.

Context: IPSS-R is used to classify risk of disease progression and guide treatment decisions for patients with MDS. Recent data shows mutational profiling may improve the prognostic stratification of MDS. Minimal real-world evidence exists for this population. Objective: Assess treatment patterns and clinical outcomes in patients with MDS by IPSS-R risk scores. Design: A retrospective cohort study assessed real-world, patient-level data from adults diagnosed with MDS between 2010–2019 at HCI. All data were obtained from electronic medical records via chart review. Patients with intermediate to very-high IPSS-R scores comprised the higher-risk cohort. Results: Of 259 patients with MDS, 90 had an IPSS-R score at diagnosis, 65 patients who were not clinical trial participants were included. IPSS-R score distribution: 10/65 (15%) very low; 18/65 (28%) low, 14/65 (22%) intermediate, 15/65 (23%) high, and 8/65 (12%) very high. Average patient age was 68 years, 52% (n=34) of patients were female, 91% (n=59) were White, 8% (n=5) had autoimmune disorders, and 5% (n=3) had cerebrovascular disease. In the higher-risk cohort, hypomethylating agents (HMAs) were used to treat 62% (n=23) of patients (median 2 cycles), while 27% (n=10) received no MDS-directed therapy and 11% (n=4) received other MDS-related medications. Stem-cell transplant (SCT) was received more frequently (n=13, 35%) and sooner (median 4.8 months from diagnosis) by higher-risk patients compared with lower-risk patients (18%, n=5; median 15.0 months from diagnosis). Complete (CR) or partial response was achieved by 17% (n=4) of higher-risk patients treated with HMAs versus 7% (n=1) of lower-risk patients. Transfusion independence was achieved by 60% (n=3) of higher-risk and 100% (n=4) of lower-risk patients who received PLT or pRBC prior to treatment initiation. Disease progression or death occurred in 82% (n=53) of patients during the study period, with a median progression-free survival of 8.3 months and 25.3 months for higher-risk and lower-risk patients, respectively. Conclusions: These results show that higher-risk patients have a low likelihood of achieving and maintaining CR. Limited treatment options for patients with higher-risk MDS reveals a large unmet need. Specific genetic profiles may indicate the need for more aggressive treatments and management of relevant comorbidities.

TPS11577 Background: Several sarcomas possess chromosomal translocations in FET family members ( FUS, EWSR1, and TAF15) responsible for cancer development. Sarcomas caused by FET family gene rearrangements include ES, desmoplastic round cell small tumors (DSRCT), myxoid liposarcoma (ML), and several others. Lysine specific demethylase 1 (LSD1) is a critical protein for sarcoma development and progression through its colocalization and/or association with several FET family oncogenic transcription factors. This suggests that pharmacologic inhibition of LSD1 may be a therapeutic strategy. Seclidemstat (SP-2577, Salarius Pharmaceuticals) is an oral, first-in-class, small molecule with reversible, noncompetitive inhibition of LSD1 (IC50: 25–50 nM). In vitro and in vivo data demonstrate seclidemstat, or analogs, modulate EWS/ETS transcriptional activity, down-regulating oncogene expression and up-regulating tumor-suppressor gene expression, leading to significant tumor growth inhibition in ES mouse xenograft studies. Seclidemstat has shown in in vitro ES cell lines near additivity efficacy when added to TC. In in vitro studies of other FET-translocated sarcomas, including ML (FUS/DDIT3 fusion) and clear cell sarcoma (EWS/ATF1 fusion), seclidemstat showed anti-proliferative activity. In an ongoing Phase 1 trial investigating single agent seclidemstat in advanced solid tumors (NCT03895684), three pts with metastatic FET-translocated sarcomas had a median progression-free survival of 5.7 months (range: 4.3–7.2) with a best response of stable disease despite having a median of 5 (range: 1–7) prior therapies. Methods: This dose expansion Phase 1 study (NCT03600649) assesses seclidemstat at 900 mg PO BID, the recommended Phase 2 dose, in two expansion cohorts: a single agent expansion in select sarcoma pts (n = 30) and a safety lead-in dose escalation and expansion (n = 24) of seclidemstat combined with TC in pts with ES. Pts must be ≥12 years old, have ECOG performance status of 0 or 1, with a life expectancy > 4 months. In the select sarcoma cohort, pts must have ML (n = 15) or other sarcomas with FET family translocations (n = 15) including DSRCT. One to 3 prior lines of therapy are allowed. In the ES combination cohort, up to 2 lines of prior therapy are allowed. Primary objective is safety/tolerability and secondary objective is efficacy. The trial is currently recruiting across 8 locations in the United States. Clinical trial information: NCT03600649.

3073 Background: Lysine-specific demethylase 1 (LSD1) is an epigenetic enzyme that is aberrantly expressed in many solid tumors. High levels of LSD1 expression are often correlated with poor patient prognosis due to LSD1’s role in cancer cell proliferation, metastasis, and chemoresistance. Seclidemstat is a novel, selective, reversible and oral LSD1 inhibitor capable of inhibiting both LSD1’s catalytic and scaffolding functions. We report preliminary efficacy in AST from an ongoing phase 1 trial. Methods: SALA-003-AC19 (NCT03895684) is a phase 1 trial of single agent SP-2577 in pts with AST. All pts had progressive disease (PD) at time of study entry. Pts received oral SP-2577 twice a day under fasting condition, in 28-day cycles (C). The primary objective is safety and tolerability. Secondary objectives are to determine maximum-tolerated dose, preliminary efficacy, pharmacokinetics, and pharmacodynamics. Results: As of December 30, 2020, 19 pts with AST (10 sarcoma, 2 prostate, 2 ovarian, 2 pancreatic, 1 renal, 1 cervical, 1 breast) were enrolled. Pts received escalating doses of SP-2577 from 150 to 600 mg BID and the dose escalation is ongoing. The median age was 63 years (range, 21–79). 42% were male, and pts had received a median of 4 (range, 1–8) prior systemic therapies. The most common (>5%) grade 3 treatment-related adverse events were GI related including diarrhea (5.3%) and abdominal pain (5.3%). No grade 4 events were reported and there were no treatment-related deaths. Safety data will be presented after completion of phase 1. Three pts had at least one dose reduction. Among the 13 pts who were evaluable for response at end of C2, 7 pts (54%) had best response of stable disease (SD) with median time to progression (TTP) of 4.3 months (range, 2.1–11.5). Four of the 7 pts had genetic abnormalities that may demonstrate increased sensitization to SP-2577 according to preclinical studies. Characteristics of 7 pts with SD at C2 and beyond are shown in the table. Conclusions: Seclidemstat has shown activity among advanced sarcoma pts with a manageable safety profile. The dose escalation is ongoing and preliminary clinical data supports further exploration in FET-translocated sarcoma as single agent and in combination therapy. Clinical trial information: NCT03895684. [Table: see text]

11514 Background: Ewing sarcoma (ES), a rare bone and soft tissue sarcoma mainly of adolescents and young adults, is characterized by a chromosomal translocation resulting in a fusion oncoprotein. Lysine specific demethylase 1 (LSD1) has been shown to associate with the fusion oncoprotein and promote oncogenic transcriptional activity making LSD1 an attractive target for ES treatment. Seclidemstat is a novel, selective, reversible oral LSD1 inhibitor capable of inhibiting both LSD1’s catalytic and scaffolding functions. This is the first report of an LSD1 inhibitor in a Phase 1 trial focused exclusively on ES. Methods: SALA-002-EW16 is a Phase 1 trial of single agent seclidemstat in patients (pts) with relapsed or refractory (R/R) ES. This report describes the completed monotherapy dose escalation. Pts > 12 years received oral SP-2577 twice daily in 28-day cycles under fasting conditions at the assigned dose level. The primary objective was safety and tolerability. Secondary objectives include to determine maximum-tolerated dose (MTD), recommended Phase 2 dose (RP2D), preliminary efficacy, pharmacokinetics, and pharmacodynamics. Results: As of December 30, 2020, 27 pts with R/R ES were enrolled. Pts received escalating doses of SP-2577 at 75 (n = 1), 150 (n = 2), 300 (n = 4), 600 (n = 6), 900 (n = 8), or 1200 mg PO BID (n = 6). The median age was 25 years (range 15–68), 63% were male, and pts had received a median of 3 (range 2–12) prior systemic therapies. There were no treatment-related deaths. The most common ( > 5%) grade 3 treatment-related adverse events (TRAEs) were vomiting (15%), abdominal pain (11%), and hypokalemia (11%). One pt (4%) with grade 3 pancreatitis reported a grade 4 AE of elevated lipase. All remaining grade 3 TRAEs, including hematological TRAEs, were reported in only one pt each. Four pts discontinued study for an AE (weight loss, pancreatitis, vomiting, abdominal pain). Three pts had a dose reduction. The first cycle dose-limiting toxicities were gastrointestinal-related AEs observed in 2 pts at 1200 mg BID. Thus, the MTD/RP2D was established as 900 mg BID. Peak plasma concentrations occurred at a median of 4 hours (h) post-dose and median terminal half-life was 6 h; exposure was dose proportional through 900 mg BID. One pt at 600 mg BID achieved a reduction in target lesions starting at end of C2 with further target lesion tumor shrinkage through end of C4 and C6 (maximum 76% tumor shrinkage) with coincident new non-target lesion appearance at end of C2. Of pts evaluable for response at the end of C2 (12 pts), two additional pts (16.7%) at 600 mg BID and 900 mg BID had overall stable disease. Conclusions: Seclidemstat has a manageable safety profile with proof-of-concept preliminary activity in heavily pretreated pts with relapsed/refractory ES. These data support the planned Phase 2 expansion of seclidemstat as single agent and in combination with chemotherapy in ES and other sarcomas that share similar translocations. Clinical trial information: NCT03600649.

e19034 Background: IPSS-R is used to classify risk of disease progression and guide treatment decisions for patients with MDS. Recent data shows mutational profiling may improve the prognostic stratification of MDS. Minimal real-world evidence exists for this population. Methods: A retrospective cohort study assessed real-world, patient-level data from adults diagnosed with MDS between 2010-2019 at HCI. All data were obtained from electronic medical records via chart review. IPSS-R scores were manually calculated from lab and cytogenetic data within 30 days of diagnosis. Patients with an intermediate to very-high IPSS-R score comprised the higher risk (HR) cohort. Primary objectives were to assess treatment patterns & clinical outcomes in the HR cohort. Results: Of the 259 MDS patients at HCI, 90 had an available IPSS-R score at diagnosis (ANC results were missing for 64% of cohort). After excluding clinical trial participants, 65 patients were included. Distribution of IPSS-R scores was: 15% very low (n = 10), 28% low (n = 18), 22% intermediate (n = 14), 23% high (n = 15), & 12% very high (n = 8). The average age of HR subjects was 67 years. 57% of HR patients were female (n = 21), 92% were white (n = 34), 8% (n = 3) had autoimmune disorders, & 8% (n = 3) had cerebrovascular disease. 14% (n = 5) of NGS-tested HR patients had TP53 alterations, while the most frequently altered gene was DNMT3A at 17% (n = 6). In the HR cohort, HMA was used to treat 62% of patients (n = 23) (median 2 cycles), while 27% (n = 10) received no MDS-related medication, and 11% (n = 4) received other MDS-related medications (lenalidomide, ruxolitinib, hydroxyurea). Second-line treatment was received by 9% of HR patients (n = 3). 35% of HR patients (n = 13) underwent stem-cell transplantation. Complete or partial response was achieved by 21% of HR patients treated with a HMA (n = 5); the remaining patients had stable disease (39%, n = 9), disease progression (26%, n = 6), or died (4%, n = 1). Transfusion independence was achieved by 60% of HMA-treated HR patients (n = 3) (median duration = 151 days from treatment initiation). Disease progression or death occurred in 89% of HR patients (n = 33) during the study period with a median progression free survival (PFS) of 8.3 months. PFS was significantly shorter for HR patients with TP53 alterations compared to wild-type (HR: 5.75, 95% CI (1.34-24.64)), using cox regression. Median overall survival for HR patients was 18.8 months. Conclusions: These results show HR patients have a low likelihood of achieving & maintaining complete remission. In addition, limited treatment options for HR patients further reveals a large unmet need. Specific genetic profiles may indicate the need for more aggressive treatments and management of relevant comorbidities. Updated results will be presented, including LR patients & economic outcomes.

e18811 Background: An open-access, web-based platform was developed to provide standardized, evidence-based information, that is cancer regimen-specific and supportive care focused. Online content was provided in the English language only for more than 200 anti-neoplastic regimens. A survey was conducted to determine reasons adult patients and their caregivers seek internet-based cancer drug information, and to evaluate if there is an unmet need for improved oncology therapy education. Methods: Between February 2020 and January 2021, patients and caregivers completed an online anonymous, English language survey deployed on the website www.chemoexperts.com. Results: A total of 1,021 website users responded. The majority of users were from North America (75%). Female respondents comprised 65% of the population and users self-identified as being a patient (67%), or family member/caregiver (33%). The mean age of respondents was 60.7 years (+ 16.2). Roughly two-thirds (66.4%) had a college degree. The majority of respondents reported they were either currently receiving (59.6%), or planning to receive (27.4%) treatment, however patients of all education levels, and in all phases of treatment (before, during, and after) sought online drug information. Clinical drug information education was reportedly provided by a doctor (68.9%), nurse (40.9%), physician assistant or nurse practitioner (23.8%), or pharmacist (15%), while 23% did not receive any education from clinical staff. Modes of education received by participants included printed material (73.9%), teaching in person (52.3%), and/or other internet sites (27.5%). Reasons for visiting the website were reported as follows: seeking additional information (92%), did not know what questions to ask (12%), looking at treatment alternatives (10%), forgot to ask questions (5%), not enough information given (11%), not enough time to ask questions (5%), and afraid to ask questions (2%). Respondents could mark all reasons. Among content sections, the percentage of users reported the side effect section as being the most useful. However, section usefulness varied based upon age, phase of treatment, and baseline education level. Overall, 86% reported finding the information they were looking for on the website. Conclusions: The majority of respondents received education from a health care provider, but not all. It is possible that the current pandemic prevented some patients from receiving education when in-person teaching was not available. However, many patients and caregivers still use the internet to seek additional drug information. These data highlight a continued unmet need for patients using online sources when searching for cancer drug and supportive care information. Further work is required to determine whether supplemental online, education can improve outcomes while reducing adverse effects.

Background Due to high survival rates and the relatively small benefit of adjuvant therapy, the application of personalized medicine (PM) through risk stratification is particularly beneficial in early breast cancer (BC) to avoid unnecessary harms from treatment. The new 21-gene assay (OncotypeDX, ODX) is a promising prognostic score for risk stratification that can be applied in conjunction with Adjuvant!Online (AO) to guide personalized chemotherapy decisions for early BC patients. Our goal was to evaluate risk-group specific cost effectiveness of adjuvant chemotherapy for women with early stage BC in Austria based on AO and ODX risk stratification. Methods A previously validated discrete event simulation model was applied to a hypothetical cohort of 50-year-old women over a lifetime horizon. We simulated twelve risk groups derived from the joint application of ODX and AO and included respective additional costs. The primary outcomes of interest were life-years gained, quality-adjusted life-years (QALYs), costs and incremental cost-effectiveness (ICER). The robustness of results and decisions derived were tested in sensitivity analyses. A cross-country comparison of results was performed. Results Chemotherapy is dominated (i.e., less effective and more costly) for patients with 1) low ODX risk independent of AO classification; and 2) low AO risk and intermediate ODX risk. For patients with an intermediate or high AO risk and an intermediate or high ODX risk, the ICER is below 15,000 EUR/QALY (potentially cost effective depending on the willingness-to-pay). Applying the AO risk classification alone would miss risk groups where chemotherapy is dominated and thus should not be considered. These results are sensitive to changes in the probabilities of distant recurrence but not to changes in the costs of chemotherapy or the ODX test. Conclusions Based on our modeling study, chemotherapy is effective and cost effective for Austrian patients with an intermediate or high AO risk and an intermediate or high ODX risk. In other words, low ODX risk suggests chemotherapy should not be considered but low AO risk may benefit from chemotherapy if ODX risk is high. Our analysis suggests that risk-group specific cost-effectiveness analysis, which includes companion prognostic tests are essential in PM. Electronic supplementary material The online version of this article (10.1186/s12885-017-3603-z) contains supplementary material, which is available to authorized users.

The advent of next generation sequencing (NGS) technologies has advanced our understanding of the intrinsic biology of different gastrointestinal (GI) tumor types. The use of novel, more efficient sequencing platforms has improved turnaround times of sequencing results. This is providing real time opportunities to put precision medicine to the test. A number of early phase clinical trials are testing targeted therapies in unique molecularly characterized subsets of patients (baskets). While basket studies are gaining momentum, treatment failures serve to remind us that shifting from a histology-driven to a histology-agnostic approach is unlikely to be a failure-free strategy for a number of tumor types as recently learnt from vemurafenib failure in BRAF mutated metastatic colorectal cancer (mCRC). GI malignancies are clinically and molecularly heterogeneous. Unfortunately, development of biomarkers of response to therapy as well as targeted therapies for GI adenocarcinomas has fallen behind compared to other malignancies. Trastuzumab is the only FDA approved targeted therapy for GI adenocarcinomas for which a biomarker of response (HER2 amplifications) is available. In addition, RAS mutations are known to predict lack of response to epidermal growth factor receptor (EGFR) inhibitors in advanced colorectal cancer (CRC) patients. However, NGS has recently revealed that a number of actionable genetic aberrations are present at low prevalence across different GI malignancies. Prospective randomized clinical trials will determine whether matching actionable aberration with targeted therapy will contribute to improve survival in patients with GI malignancies. Here, we review current evidence for targeted therapies in GI malignancies, as well as application and pitfalls of NGS including tissue testing and liquid biopsies.

Purpose Hand-foot syndrome is a common dose limiting toxicity of vascular endothelial growth factor receptor tyrosine kinase inhibitors used for treatment of patients with metastatic renal cell carcinoma. The effect of treatment dose reductions, in the context of hand-foot syndrome, on survival outcomes is reported. Methods This was a retrospective case series of patients receiving vascular endothelial growth factor receptor tyrosine kinase inhibitors from 1 January 2004 to 31 October 2013. The main outcomes were progression-free and overall survival in these patients experiencing hand-foot syndrome and undergoing treatment dose reductions. Univariate and multivariate analyses were conducted utilizing Kaplan-Meier method and COX Proportional Hazard model with landmark analyses at 2 months. Results Of the 120 patients evaluated, treatment dose reductions for any reason were required in 68 (56.7%) patients. The most common reasons for treatment dose reductions were mucositis, hand-foot syndrome, and fatigue. The median progression-free survival and overall survival were significantly longer in patients with hand-foot syndrome with or without treatment dose reductions as compared to those without hand-foot syndrome. Conclusions An improvement in survival outcomes was observed in metastatic renal cell carcinoma patients with treatment-associated hand-foot syndrome despite treatment dose reductions. These data need validation in a larger cohort to confirm the hypothesis that treatment dose reductions in the setting of hand-foot syndrome do not negatively impatient survival.

OBJECTIVES/GOALS: This project seeks to understand how personalized medicine can optimize care for patients with colorectal cancer. It identifies opportunities for personalized medicine to improve clinical outcomes, and uses cost-effectiveness analysis to assess the clinical and financial impact of this approach. METHODS/STUDY POPULATION: This project uses two methods to understand the impact of personalized medicine. First, this project has used SEER-Medicare data in conjunction with Clinical Pharmacogenetics Implementation Consortium guidelines to identify medications used by patients with colorectal cancer that can be impacted by genetic variants. This data will then be combined with population genetic variant rates to understand the likely impact screening for a given variant will have on medication response and adverse events. Medication use frequencies and genetic variant rates are then used to populate cost-effectiveness models that simulate the clinical and financial outcomes, identifying optimal genes to screen. RESULTS/ANTICIPATED RESULTS: The first result will be a comprehensive overview of treatment patterns for patients with colorectal cancer in the United States, as well as the treatments used for disease-induced comorbidities. The second result will be the identification of genetic variants based on population rates and medication utilization that should be screened in this patient population. The final result will be a breakdown of the clinical and financial outcomes associated with implementing screening for the identified genes. Preliminary results from a two-gene cost-effectiveness analysis demonstrates that screening for variants in those genes improves both clinical and financial outcomes. DISCUSSION/SIGNIFICANCE OF IMPACT: This project demonstrates how current treatment approaches can be optimized via personalized medicine. It uses epidemiological methods to identify opportunities to integrate genetic findings from other diseases, and uses cost-effectiveness analysis to understand the impact of transforming care. CONFLICT OF INTEREST DESCRIPTION: Stocks-Aurinia, Syndax, Adaptimmune, Rigel pharma

Purpose Contemporary treatment for metastatic hormone sensitive prostate cancer (mHSPC) includes androgen deprivation therapy (ADT) plus abiraterone or docetaxel. While these intensified regimens have improved efficacy, they are also associated with increased cost and toxicities. Not all men with mHSPC may be candidates for these intensified regimens, yet there are no clinical models or biomarkers used to optimize treatment selection. Herein, we hypothesized that longer time from prior definitive therapy (DT), either radical prostatectomy, definitive radiotherapy, or both, to onset of metastatic disease is associated with improved survival outcomes in men with newly diagnosed mHSPC. Methods This multicenter retrospective study included men initiating systemic therapy with ADT for new mHSPC. Kaplan-Meier and COX proportional hazard models assessed time to metastatic castration-resistant prostate cancer (mCRPC) and overall survival (OS) by receipt of prior DT. Results Of the 253 men with new mHSPC, 115 (45%) had received prior DT. In a multivariate analysis, increasing years from DT to the start of ADT was an independent predictor of time to mCRPC (per year: hazard ratio 0.91 95% confidence interval 0.84–0.99, P = 0.020) and improved OS (per year: hazard ratio 0.87, 95% confidence interval 0.74–0.99, P = 0.0025) in patients with new mHSPC, and may assist with risk stratification in these patients at time of mHSPC. Conclusion Time from DT to start of ADT is an independent predictor of time to mCRPC and OS in men with new mHSPC, and may assist with risk stratification of these patients for systemic therapy selection.

Supplemental Digital Content is available in the text., New melanoma therapies have shifted the expectations of patients and providers. Evaluating the impact of treatment characteristics may enhance shared decision making. A survey, including a discrete choice experiment, was utilized to evaluate perceived trade-offs of different melanoma treatments and to estimate out-of-pocket (OOP) willingness-to-pay (WTP) thresholds (January 2016 to March 2016). Participants included patients with melanoma at Huntsman Cancer Institute and their cancer care providers. Stakeholder focus groups were conducted to identify treatment attributes. Descriptive and comparative statistics and multinomial logit model were used to evaluate responses. Response rates were 41.9% (N = 220) for patients and 37.7% (N = 20) for providers. Immunotherapy and targeted therapy attributes considered important by participants were overall survival, immunotherapy-related side effects, and skin toxicities. Patients and providers had significantly different views of quality-of-life expectations, anxiety toward melanoma, trust to make treatment decisions, sharing concerns about treatment, time to discuss treatment, understanding OOP costs, and willingness to undergo/recommend treatment (half of the patients would undergo treatment if it was effective for > 24 months). Among patients, the average monthly OOP WTP for combination immunotherapy with nivolumab + ipilimumab was $ 2357 and for BRAF/MEK inhibitor was $1648. Among providers, these estimates were $ 2484 and $1350, respectively. Discordance existed between patients’ and providers’ perceptions about quality of life expectations, degree of anxiety, sharing of opinions, and progression-free survival. Our study suggests that patients and providers exhibit a higher OOP WTP for combination immunotherapy treatment compared with BRAF/MEK inhibitors, influenced predominately by overall survival expectations.

Background First-line treatment for metastatic renal cell carcinoma (mRCC) is rapidly changing. It currently includes VEGF targeted therapies (TT), multi-target tyrosine kinase inhibitors (TKIs), mTOR inhibitors, and immunotherapy. To optimize outcomes for individual patients, genomic markers of response to therapy are needed. Here, we aim to identify tumor-based genomic markers of response to VEGF TT to optimize treatment selection. Methods From an institutional database, primary tumor tissue was obtained from 79 patients with clear cell mRCC, and targeted sequencing was performed. Clinical outcomes were obtained retrospectively. Progression-free survival (PFS) on first-line VEGF TT was correlated to genomic alterations (GAs) using Kaplan-Meier methodology and Cox proportional hazard models. A composite model of significant GAs predicting PFS in the first-line setting was developed. Results Absence of VHL mutation was associated with inferior PFS on first-line VEGF TT. A trend for inferior PFS was observed with GAs in TP53 and FLT1 C/C variant. A composite model of these 3 GAs was associated with inferior PFS in a dose-dependent manner. Conclusion In mRCC, a composite model of TP53 mutation, wild type VHL, and FLT1 C/C variant strongly predicted PFS on first-line VEGF TT in a dose-dependent manner. These findings require external validation.

Background Targeted therapies have shown promise for men with metastatic castration-resistant prostate cancer (mCRPC). Due to the difficulty with obtaining tumor tissue in bony metastases, liquid biopsies are a promising alternative to guide treatment selection. While concurrent tissue next-generation sequencing (tNGS) and liquid biopsy has high concordance, it is unknown whether the genomic landscape of metastatic prostate cancer (mPC) changes over time or treatment. Herein, we hypothesize that the genomic landscape of mPC evolves with new treatments and/or time between tests. Patients and Methods Men with mPC from the University of Utah with matched tNGS and liquid biopsy were included. Clinical data was collected retrospectively. Exonic regions from 69 genes covered by both platforms were included for analysis. Paired t tests were used to assess number of genomic alterations (GAs) between testing platforms. Number of alterations was assessed by time and number of treatments between testing by multivariate nonparametric trend tests. Results 101 men with mPC were eligible and included. In men with no new treatments and ≤ 1 year between tests, a similar number of GAs were detected in both tests (2.0 vs. 2.2). In contrast, men with ≥ 1 new treatment between tests had significantly more GAs after treatment (5.0 vs. 2.4, p = 0.005). Total number of GAs was correlated with number of new treatments between testing (p = 0.003) and not time between testing (p = 0.76). Conclusion The genomic landscape of mPC evolves with subsequent therapies. This finding suggests that contemporary tumor genomic profile upon disease progression may optimize guidance towards subsequent therapy selection.

Clinical pharmacists are important contributors to the care of patients with cancer; it is therefore critical for oncology clinical pharmacists to stay current with new anticancer therapies. This review summarizes the epidemiology and pathogenesis of non-small cell lung cancer, including the most common genetic alterations, as well as the mechanism of action, clinical development, pharmacodynamics and pharmacokinetics of the anaplastic lymphoma kinase inhibitor ceritinib for the treatment of patients with anaplastic lymphoma kinase-positive non-small cell lung cancer. Targeted therapies based on the presence of specific mutations are an important development in the treatment of non-small cell lung cancer. However, acquired resistance to the first anaplastic lymphoma kinase-inhibitor approved by the U.S. Food and Drug Administration, crizotinib, is observed in almost half of patients treated with it. Ceritinib is an oral anaplastic lymphoma kinase-inhibitor that has demonstrated more potent antitumor activity than crizotinib in preclinical models. It was granted accelerated approval in 2014 to treat anaplastic lymphoma kinase-positive metastatic non-small cell lung cancer patients who have progressed on or are intolerant to crizotinib. Ceritinib represents an important alternative second-line therapy for patients with metastatic non-small cell lung cancer who have traditionally limited treatment options.