Aim: To validate ConcertAI's All Source Composite Mortality Endpoint (ASCME), which combines information from electronic health records, obituary, government and administrative claims. To compare overall survival (OS) estimates using ASCME versus a National Death Index (NDI) dataset across clinical cohorts. Materials & methods: Retrospective study of oncology real-world data, reporting sensitivity, specificity, positive predictive value and negative predictive value compared with the NDI standard, plus 5, 7 and 15-day concordance on date of death. Additional comparisons included Kaplan-Meier OS measured by ASCME versus NDI. Data sources included ConcertAI's Patient360™ dataset, and a 2022 annual finalized NDI dataset. The sample included cancer patients prevalent from 1 April 2014 to 31 December 2022 in any of 10 of ConcertAI's solid tumor-specific datasets. Results: Of 32,358 study patients, 14,241 (44.0%) were deceased as defined by an NDI true match. Sensitivity was 95.0% overall (an incremental 5.2% due to claims) and ranged from 92.7% to 97.8% across clinical cohorts. Overall specificity was 96.5%, with positive predictive value and negative predictive value of 95.8% each. ASCME's 5-day concordance was 97.9%, with 7-day and 15-day concordance of 98.2% and 99.1%, respectively. ASCME and NDI-based median OS estimates differed by 12.2 days among non-metastatic cohorts, and 4.5 days among metastatic cohorts. Conclusion: Results show ConcertAI's ASCME death indicator to provide high completeness and accuracy, producing OS estimates largely indistinguishable from NDI-based estimates. Findings show the importance of including claims in composite mortality indicators and demonstrate the value of real-world data in assessing OS outcomes in metastatic and non-metastatic cancer patient populations.

Introduction: Recent advances in genomic research have expanded the treatment landscape for acute myeloid leukemia (AML). This study examined treatment patterns and clinical outcomes among relapsed/refractory (R/R) FMS-like tyrosine kinase 3 (FLT3)-mutated AML patients. METHODS:This retrospective longitudinal study included patients with confirmed AML diagnosis, FLT3 mutation, and 1st R/R event from 1/1/2015 to 1/31/2023 in the ConcertAI Oncology Dataset. Treatment patterns, FLT3 testing rates, real-world overall survival (rwOS), and real-world time to next treatment (rwTTNT) were studied. RESULTS:Among the 336 treated patients, 50.6% received FLT3-tyrosine kinase inhibitors (FLT3-TKIs) as first treatment after R/R event, of which 51.8% received gilteritinib. High-intensity chemotherapy used as first treatment after R/R event decreased from 67.9% in 2015 to 20.0% in 2022, while FLT3-TKI utilization rose to 50% over the same period. Among the 246 patients tested for FLT3 at initial AML diagnosis, only 36% were retested at 1st R/R event. Median rwOS and rwTTNT among FLT3-TKI patients were 12.4 months and 2.9 months, respectively. CONCLUSION:This study reveals a trend toward increasing FLT3-TKI use and highlights the need for repeated FLT3 testing among R/R AML patients. Real-world evidence is vital in understanding R/R AML patient care amidst emerging therapies. .

Gold standards used in validation of new tests may be imperfect, with sensitivity or specificity less than 100

Supplementary Table 1: List of Individual Symptoms Used Included in Composite Scores

Supplementary Table 2: List of HCPCS Codes to Identify Chemotherapy

Supplementary Table 4: Kitagawa-Blinder-Oaxaca Decomposition of Race Differences in one-SD Increases of Composite Scores among Patients with Surgery Date Identified

Supplementary Figure 1: Sample selection flow chart. * Note: This figure shows how the study inclusion and exclusion criteria were applied to derive the final primary study cohort, and the additional criteria used for the subgroup cohorts included in sensitivity analyses. Each box represents one inclusion or exclusion criterion with the corresponding sample size. Abbreviations: PCM = Patient Care Monitor, FFS = Fee-For-Service

Supplementary Table 3: Kitagawa-Blinder-Oaxaca Decomposition of Race Differences in one-SD Increases of Composite Scores among Medicare Beneficiaries Subsample

Supplementary Table 5: Kitagawa-Blinder-Oaxaca Decomposition of Race Differences in one-SD Increases of Composite Scores among Patients Receiving At Least 4 Cycles of Chemotherapy

AbstractBackground: Symptom burden differences may contribute to racial disparities in breast cancer survival. We compared symptom changes from before to during chemotherapy among women with breast cancer. Methods: This observational study followed a cohort of Black and White women diagnosed with Stage I–III, hormone receptor–positive breast cancer from a large cancer center in 2007 to 2015, and reported symptoms before and during chemotherapy. We identified patients who experienced a one-standard deviation (SD) increase in symptom burden after starting chemotherapy using four validated composite scores (General Physical Symptoms, Treatment Side Effects, Acute Distress, and Despair). Kitagawa–Blinder–Oaxaca decomposition was used to quantify race differences in symptom changes explained by baseline characteristics (sociodemographic, baseline scores, cancer stage) and first-line chemotherapy regimens. Results: Among 1,273 patients, Black women (n = 405, 31.8%) were more likely to report one-SD increase in General Physical Symptoms (55.6% vs. 48.2%, P = 0.015), Treatment Side Effects (74.0% vs. 63.4%, P < 0.001), and Acute Distress (27.4% vs. 20.0%, P = 0.010) than White women. Baseline characteristics and first-line chemotherapy regimens explained a large and significant proportion of the difference in Acute Distress changes (93.7%, P = 0.001), but not General Physical Symptoms (25.7%, P = 0.25) or Treatment Side Effects (16.4%, P = 0.28). Conclusions: Black women with early-stage breast cancer were more likely to experience significant increases in physical and psychological symptom burden during chemotherapy. Most of the difference in physical symptom changes remained unexplained by baseline characteristics, which suggests inadequate symptom management among Black women. Impact: Future studies should identify strategies to improve symptom management among Black women and reduce differences in symptom burden. See related commentary by Rosenzweig and Mazanec, p. 157

Abstract Background Real-world data regarding patient characteristics, adjuvant treatment patterns, and long-term survival outcomes are needed to better understand unmet needs among patients with completely resected early-stage non-small cell lung cancer (NSCLC). Methods Electronic medical records from the U.S.-based ConcertAI Patient360™ database were analyzed in patients with stage IB-IIIA NSCLC who underwent complete resection prior to March 1, 2016. Patients were followed until death or July 1, 2021. This study evaluated adjuvant chemotherapy use, and overall survival (OS) and real-world disease-free survival (rwDFS) outcomes using the Kaplan–Meier method. The correlation between OS and rwDFS was assessed using the Kendall rank test. Among patients who did not recur 5 years following surgery, landmark analyses of OS and rwDFS were conducted to understand the subsequent survival impact of remaining disease-free for at least 5 years. Results Data from 441 patients with completely resected stage IB-IIIA NSCLC were included. About 35% of patients received adjuvant chemotherapy post-resection. Median OS and rwDFS from resection were 83.1 months and 42.4 months, respectively. The 5-year OS and rwDFS rates were 65.7% and 42.1%, respectively. OS and rwDFS were positively correlated (Kendall rank correlation coefficient = 0.67; p < 0.0001). Among patients without recurrence within 5 years after resection, the subsequent 5-year OS and rwDFS survival rates were 52.9% and 36.6%, respectively. Conclusions Use of adjuvant chemotherapy was low, and the overall 5-year OS rate remained low despite all patients having undergone complete resection. Patients who remained non-recurrent over time had favorable subsequent long-term survival.

Aim: To evaluate the comparability of a probable clinical trial (CT) cohort derived from electronic medical records (EMR) data with a real-world cohort treated with the same therapy and identified using the same inclusion and exclusion criteria to emulate an external control. Methods: We utilized de-identified patient-level structured data sourced from EMRs. We then compared patterns of overall survival (OS) between probable CT patients with those drawn from non-contemporaneous real-world data (RWD) using a two-sided log-rank test, hazard ratios (HRs) using a Cox proportional-hazards model and Kaplan–Meier (KM) survival curves. Each regression estimate was calculated with a corresponding 95% confidence interval. We additionally conducted multiple matching methods to assess their relative performance. Results: Median (standard deviation) OS was 10.2 (0.7) months for the RWD arm and 11.3 (1.3) for the probable CT arm with a Log rank p-value equal to 0.4771. OS in both cohorts is longer than the reported CT median OS of 9.2 (0.6). The HRs generated under all five assessed matching methods (including without adjustment) were not statistically significant at the 95% confidence level. Conclusion: Our results suggest, with caveats noted, that survival patterns between real-world and CT cohorts in this NSCLC setting are not statistically significantly different.

Background: Optimal treatment for patients with stage IIIA NSCLC is controversial. Growing evidence indicates surgery with adjuvant or neoadjuvant chemotherapy (SC) may be superior to non-surgical treatments. Direct comparisons have not been performed between SC and chemoradiation with immunotherapy (CRI) among patients diagnosed with stage IIIA NSCLC since consolidation immunotherapy was added to treatment guidelines. Methods: This retrospective study compared surgical and systemic non-surgical treatments (except targeted therapy) among adults diagnosed with stage IIIA NSCLC 2017-2021. Data was from ConcertAI's curated EHR Patient360TM NSCLC real-world care product. Real-world progression-free survival (rwPFS) and overall survival (rwOS) were evaluated among patients treated with SC or CRI using Kaplan-Meier and Cox proportional hazard methods. Baseline differences were balanced using propensity score-derived inverse probability treatment weights (IPTW). Results: Among 1718 eligible, the two main comparator groups (SC and CRI) had 431 (25%) and 576 (34%) patients; 711 patients received chemoradiation or monotherapy. A wide range of treatment strategies was observed across included oncology clinics (e.g., 0-67% clinic patients received surgery). IPTW-adjusted analyses showed reduced hazards in the SC group vs. CRI for rwPFS (HR 0.78, 95% CI: 0.63-0.97) and rwOS (HR 0.63, 95% CI: 0.49-0.82). SC was similarly beneficial for patients across nodal status groups and appeared especially beneficial for patients with resectable squamous-cell tumors. Conclusion: Stage IIIA NSCLC treatment is highly variable. Real-world studies can provide valuable evidence to support surgery as a treatment option for stage IIIA patients, who currently may only be offered chemoradiation with or without immunotherapy.

Aim: Real-world data on outcomes for early-stage non-small-cell lung cancer (NSCLC) are needed to better understand the benefits of new therapies. Methods: In this retrospective study using the ConcertAI Patient360™ database, overall survival and healthcare resource utilization were compared among patients with recurrent and non-recurrent completely resected stage IB-IIIA NSCLC. Results: Recurrence was associated with a shorter median overall survival compared with non-recurrence (31.5 months vs 75.6 months, respectively), lower survival probability 5-years post-resection, and higher healthcare resource utilization. Patients with late recurrence had a longer restricted mean survival time versus patients with early recurrence. Conclusion: Results from this real-world study highlight the potential value of preventing or delaying recurrence in patients with early-stage NSCLC.

Aim: We evaluated outcomes of first-line (1L) treatment of metastatic breast cancer (mBC) by biomarker subtype in the community setting over the last decade. Methods: Eligible patients (N = 1,518) were female, >= 18 years, diagnosed with mBC 2010 or later, had documented HR+/HER2-, HER2+, or triple negative breast cancer (TNBC); and initiated 1L therapy. Kaplan-Meier and Cox methods were used to evaluate 1L real-world progression-free survival (rwPFS) and overall survival (OS) from start of 1L. Results: TNBC was diagnosed at an earlier stage and had higher tumor grade at initial diagnosis. 1L rwPFS and OS from start of 1L were shorter for TNBC than HR+/HER2- or HER2+. Conclusion: Overall prognosis for patients with metastatic TNBC remains poor, and new therapies are needed to improve clinical outcomes. Plain language summary What is this article about?This study looked at how well women with metastatic breast cancer did after starting treatment. It compared three groups. The first group had tumors that respond to hormone therapy. The second group had tumors that respond to treatment that works on a specific protein. A third group had tumors that don't respond to either of those - called triple negative. The study looked at women 18 and older who had metastatic breast cancer in 2010 or later. They had all been treated at a community oncology practice. We looked at how long it took for the cancer to get worse, and how long until patients died, for each of the three groups. What were the results?There were 1518 patients in the study. Most (62.5%) were in the group that responds to hormone therapy. The rest had tumors that respond to treatment that works on the specific protein (23.4%), or had triple negative tumors (14.1%). Patients with triple negative tumors were diagnosed earlier, but they had worse tumor characteristics. They also had shorter time until their cancer got worse, and they did not live as long, compared with the other groups. What do the results of the study mean?This builds on other studies by showing that, even in a modern era, outcomes are poor for patients with triple negative breast cancer. It shows that new treatments are needed for patients with triple negative breast cancer.

The purpose of this study was to evaluate the potential collective opportunities and challenges of transforming real-world data (RWD) to real-world evidence for clinical effectiveness by focusing on aligning analytic definitions of oncology end points. Patients treated with a qualifying therapy for advanced non-small cell lung cancer in the frontline setting meeting broad eligibility criteria were included to reflect the real-world population. Although a trend toward improved outcomes in patients receiving PD-(L)1 therapy over standard chemotherapy was observed in RWD analyses, the magnitude and consistency of treatment effect was more heterogeneous than previously observed in controlled clinical trials. The study design and analysis process highlighted the identification of pertinent methodological issues and potential innovative approaches that could inform the development of high-quality RWD studies.

e13045 Background: Limited studies exist comparing methods for HER2 status determination using real-world data (RWD). Results of metastatic breast cancer (MBC) patients with Next Generation Sequencing (NGS) within the ConcertAI Genome360 dataset with DNA sequencing were compared to the standard immunohistochemistry (IHC) or in-situ hybridization (ISH) or both IHC and ISH for HER2 status. Methods: Patients diagnosed with MBC, with HER2 status determined with NGS DNA sequencing, IHC, or any of the ISH tests, by various laboratories within 2 months of each other, from August 19, 2011 to March 9, 2021, were analyzed. Patients were classified as positive, negative, or equivocal based on each of the testing methods. Comparisons were made between DNA sequencing and IHC results, DNA and ISH results, and DNA and IHC and subsequent ISH results. Results: The study sample included 252 patients (99% female, mean age [SD] of 62 [11.93]) with 382 test combinations as follows: 220 (58%) with DNA sequencing and IHC results, 127 (33%) with DNA sequencing and ISH results, and 35 (9%) with DNA sequencing and IHC and ISH results. Of the 220 combinations with DNA sequencing and IHC results, 15 were uniformly considered HER2+, 160 HER2-, and 1 equivocal, while 44 differed in the results, resulting in 80% match rate. Of the 127 combinations with DNA sequencing and ISH results, 14 were HER2+ and 96 HER2-, while 17 differed, resulting in 87% match rate. Of the 35 combinations with DNA sequencing and IHC and ISH, 3 were HER2+ and 26 were HER2-, while 6 differed, resulting in 83% match rate. Match rate was significantly higher for patients with negative results, than positive results. Specimen type, site, and type of expression had no impact on match rates. Conclusions: RWD indicate relatively high level of match rate among DNA sequencing, IHC, and ISH results in MBC patients. However, 13-20% of the combinations did not match. For these patients, mechanisms to reach consensus need to be explored to determine optimal treatments.

6528 Background: Symptom burden may contribute to racial differences in cancer treatment adherence and survival. Evidence on changes in symptom burden during chemotherapy and whether these differ by race is scarce. We used patient reported outcomes data collected before and after breast cancer chemotherapy initiation to compare symptom burden by race. Methods: Using electronic medical records of a large cancer center in the southern region of the US, we identified Black and White women diagnosed with stage I-III, hormone-receptor positive breast cancer from January 2007 to December 2015. A tablet-based platform [ConcertAI] was used to collect patient reported symptoms at the point of care. We included patients with at least one completed symptom report before and during chemotherapy. We focused on two standardized composite scores – physical symptoms and treatment side-effect (mean of 50 and standard deviation of 10), and calculated changes in symptoms using the closest report before chemotherapy and the most severe score reported during chemotherapy. Patients with a 10-point increase were classified as having a clinically meaningful increase in symptom burden. We used Oaxaca-Blinder decomposition to quantify racial differences in symptom burden change explained by baseline characteristics. These included baseline symptom scores, sociodemographic characteristics (age, regional level household income and education, state) and clinical characteristics (cancer stage and primary chemo regimen). Results: Among 1,167 included patients, Black women (30%) were younger (52 vs. 55 years old, p<.001), more likely to live in areas with lower median household income and less education, and reported most severe scores about 2 weeks later than White women ( p<.05). They were also more likely to report a 10-point increase in symptom burden for physical (68.5% vs. 61.2%, p=.017) and side-effects symptoms score (49.0% vs. 41.4%, p=.015). This was driven by larger increases in selected individual symptoms among Black women, such as sweating, itching, and numbness (under physical symptom score), and hair loss and taste change (under side-effect score). Decomposition analyses showed that baseline characteristics (especially primary chemo regimen) explained 79.2% ( p=.002) and 35.2% ( p=.131) of the increased probability of Black women reporting a 10-point increase in physical symptom and side-effects scores respectively. Conclusions: Black women with early-stage breast cancer were more likely to report a clinically meaningful increase in treatment side-effects and physical symptoms during chemotherapy compared to White women. Differences by race in physical symptoms scores were mostly explained by baseline characteristics. Future studies should examine whether racial differences in symptom burden translate into differences in treatment adherence and mortality.

Importance:Adjuvant endocrine therapy (AET) reduces breast cancer recurrence, but symptom burden is a key barrier to adherence. Black women have lower AET adherence and worse health outcomes than White women.Objective:To investigate the association between symptom burden and AET adherence differences by race.Design, Setting, and Participants:A retrospective cohort study using electronic health records with patient-reported data from a large cancer center in the US. Patients included Black and White women initiating AET therapy for early-stage breast cancer from August 2007 to December 2015 who were followed for 1 year from AET initiation. Sixty symptoms classified into 7 physical and 2 psychological symptom clusters were evaluated. For each cluster, the number of symptoms with moderate severity at baseline, and symptoms with 3-point or greater increases during AET were counted. Adherence was measured as the proportion of days covered by AET during the first-year follow-up. Multivariable regressions for patients' adherence adjusting for race, symptom measures, sociodemographic characteristics, and clinical characteristics were conducted. Kitagawa-Blinder-Oaxaca decomposition was used to quantify racial differences in adherence explained by symptoms and patient characteristics. Analyses were conducted from July 2021 to January 2022.Exposures:Physical and psychological symptoms at baseline and changes during AET.Results:Among 559 patients (168 [30.1%] Black and 391 [69.9%] White; mean [SD] age 65.5 [12.1] years), Black women received diagnoses younger (mean [SD] age at diagnosis, 58.7 [13.7] vs 68.5 [10.0] years old) than White women, with more advanced stages (30 Black participants [17.9%] vs 31 White participants [7.9%] had stage III disease at diagnosis), and lived in areas with fewer adults attaining high school education (mean [SD], 78.8% [7.8%] vs 84.0% [9.3%]). AET adherence in the first year was 78.8% for Black and 82.3% for White women. Black women reported higher severity in most symptom clusters than White women. Neuropsychological, vasomotor, musculoskeletal, cardiorespiratory, distress, and despair symptoms at baseline and increases during the follow-up were associated with 1.2 to 2.6 percentage points decreases in adherence, which corresponds to 4 to 9 missed days receiving AET in the first year. After adjusting for psychological symptoms, being Black was associated with 6.5 percentage points higher adherence than being White.Conclusions and Relevance:In this cohort study, severe symptoms were associated with lower AET adherence. Black women had lower adherence rates that were explained by their higher symptom burden and baseline characteristics. These findings suggest that better symptom management with a focus on psychological symptoms could improve AET adherence and reduce racial disparities in cancer outcomes.