Real-world Database Research Articles

Predicting Mortality Risks Using Body Mass Index and Weight Loss at Admission in Patients with Heart Failure.

The association of the combination of body mass index (BMI) and weight change at admission with prognoses in patients with heart failure (HF) is unclear. Therefore, we investigated whether BMI and weight changes at admission affect mortality in patients with HF. This retrospective cohort study lasted 99 months, starting in April 2014, and included 4,862 patients with HF from a Japanese real-world database. Cubic and thin-plate smoothing spline analyses were performed to investigate the association of BMI and weight changes with mortality. The percentage weight change was calculated every 6 months. The study outcome was the presence or absence of death. The patients' mean age was 81.5±9.6 years, and 1,239 (25.5%) patients died. Cubic spline analysis revealed a negative correlation of BMI with mortality hazard ratio (HR) (BMI of 18.5 kg/m2 and 25 kg/m2; HR=1.3 [1.2-1.4] and 0.8 [0.7-0.9], respectively). Cubic spline analysis of weight change showed that weight loss tended to increase the mortality HR (each 6% decrease in weight change rate was associated with a 1.1 times higher mortality risk (95% CI [1.0-1.2]) Thin-plate smoothing spline analysis showed that the odds ratio (OR) negatively correlated with BMI (1-year mortality: BMI of 18.5 kg/m2, 22 kg/m2, and 25 kg/m2; OR at 0% weight change=1.5, 1.0, and 0.7, respectively; 2-year mortality: BMI=18.5 kg/m2, 22 kg/m2, and 25 kg/m2; OR at 0% weight change=1.4, 0.9, and 0.7, respectively). A low BMI in patients with HF was associated with a higher risk of mortality. Weight loss in patients, regardless of BMI, was associated with a higher OR for mortality.

Effect of a novel artificial intelligence (AI) –enabled multi-trial matching system on patient matching using real-world data.

e13501 Background: Currently clinical research teams at sites are manually matching patients to clinical trials, where each trial in our experience takes at least 25 minutes using highly trained dedicated resources. This limits cancer patients’ clinical trial options and enrollment rates. Moreover, the lack of NGS testing results may also negatively impact matching to clinical trials in targeted therapies. PCC, a consortium of 7 of the Top 20 Pharmaceutical companies, collaborated with Massive Bio to demonstrate how cancer patients’ matching rates can be increased if patients are prescreened to multiple trials simultaneously (i.e. multi-trial matching) instead of a single trial and NGS testing results are integrated into the matching process. Methods: Massive Bio has developed a first-in-class AI-enabled matching system to extract 180 structured clinical data from medical records using computer vision and natural language processing and a recommendation system for matching patients to parameterized inclusion/exclusion (I/E) criteria from over 14,000 actively recruiting interventional clinical trials.Our analysis included a sample of 5,707 cancer patients from the Massive Bio Synergy AI real-world database, corresponding to tumor types in 23 selected trials. We developed a decision-tree algorithm for retrospective matching analysis using modeled I/E criteria and compared these results to the theoretical matching rate (TMR) for each trial based on tumor type and biomarker prevalence, extent of disease at diagnosis and prior treatment history. Results: 690 patients matched to at least one trial were matched to 1.82 times more trials in multi-trial matching; 2.10 times more potential matches were obtained with hypothetical 100% NGS testing; and 99.9% matching time was reduced with AI enabled system; key findings are summarized (Table). Conclusions: This study confirms the underutilization of NGS technology and substantial benefits of AI and NGS in cancer trial matching. Their use resulted in a nearly two-fold increase in potential patient eligibility for trials, and an unprecedented reduction in manual effort, underscoring a significant advancement in the efficiency of the clinical trial matching process. A prospective country-wide analysis is under consideration. [Table: see text]

Effect of maintenance therapy (MT) on real-world outcomes (RWO) of patients (pts) with newly diagnosed multiple myeloma (NDMM) post stem cell transplant (SCT).

7562 Background: SCT followed by MT is the standard of care for pts with transplant-eligible (TE) NDMM. Five randomized clinical trials (RCTs) comparing lenalidomide MT versus no MT showed improved progression free survival (PFS), but no overall survival (OS) benefit except for one by McCarthy et al. that allowed pt crossover between treatment arms. Use of MT has also been associated with an increased risk of second primary malignancies and an inferior quality of life. We report RWO post SCT with and without MT in TE NDMM. Methods: We performed a multi-center, retrospective, observational study using the de-identified COTA real-world database derived from the EMRs of US centers. Pts with NDMM from 1/1/2012 to 1/1/23 were included in the study. Kaplan-Meier method was used to evaluate time to next treatment (TTNT), OS, follow-up time (reverse OS endpoint), and report log-rank test p-values. TTNT was defined in two ways: time from SCT to the earliest of initiation of next line of therapy (LOT) or death (TTNT1) and the time from 2nd LOT post-SCT to the earliest of initiation of next LOT or death (TTNT2). A propensity score (PS) matched analysis was used to compare study cohorts and report hazard ratios (HRs) using the Cox proportional hazards method. High risk cytogenetic abnormalities (HRCA) were defined as pts with 17p(-), t(4;14), t(14;16), t(14;20) and 1q+. Results: 1928 ptsmet the study criteria: 957 pts received SCT with MT (M) and 971 pts received no MT (NM). Median age at Dx was 61 y, 57% were male, 70% were White, and 31.2% had HRCA with a median follow-up of 64 months (mos) (95% CI: 61.6, 66.7). In the M vs NM arms, 29.6% and 32.7% pts had HRCA, respectively. Median TTNT1 for M vs NM was 51 vs 36 months (mos), (p<0.001), respectively. Median TTNT2 for M vs NM was 11.7 vs 21.6 mos, (p<0.001), respectively. Median OS for M vs NM was 108.8 mos vs 126.3 mos, (p=0.08), respectively. In the PS model, the NM group had significantly lower hazard of TTNT2 and OS events (HRs 0.65 and 0.85, p<0.001 and p=0.08, respectively). Conclusions: Our study demonstrates improved TTNT2 outcomes with the NM approach. M therapy did not have an impact on OS in this cohort. Both results indicate an absence of long-term benefit with the use of M therapy. OS is a difficult primary outcome to achieve in MM RCTs where survival may have to be collected for decades. Thus, our large study of RWO with long-term follow-up is valuable. [Table: see text]

Clinical networking results in continuous improvement of the outcome of patients with acute promyelocytic leukemia

AbstractThe introduction of all-trans retinoic acid combined with anthracyclines has significantly improved the outcomes for patients diagnosed with acute promyelocytic leukemia (APL), and this strategy remains the standard of care in countries in which arsenic trioxide is not affordable. However, data from national registries and real-world databases indicate that low- and middle-income countries (LMIC) still face disappointing results, mainly because of high induction mortality and suboptimal management of complications. The American Society of Hematology established the International Consortium on Acute Leukemias (ICAL) to address this challenge through international clinical networking. Here, we present the findings from the International Consortium on Acute Promyelocytic Leukemia study involving 806 patients with APL recruited from 2005 to 2020 in Brazil, Chile, Paraguay, Peru, and Uruguay. The induction mortality rate has notably decreased to 14.6% compared with the pre-ICAL rate of 32%. Multivariable logistic regression analysis revealed as factors associated with induction death: age of ≥40 years, Eastern Cooperative Oncology Group performance status score of 3, high-risk status based on the Programa Español de Tratamiento en Hematologia/Gruppo Italiano Malattie EMatologiche dell'Adulto classification, albumin level of ≤3.5 g/dL, bcr3 PML/RARA isoform, the interval between presenting symptoms to diagnosis exceeding 48 hours, and the occurrence of central nervous system and pulmonary bleeding. With a median follow-up of 53 months, the estimated 4-year overall survival rate is 81%, the 4-year disease-free survival rate is 80%, and the 4-year cumulative incidence of relapse rate is 15%. These results parallel those observed in studies conducted in high-income countries, highlighting the long-term effectiveness of developing clinical networks to improve clinical care and infrastructure in LMIC.

Validation and development of population pharmacokinetic model of vancomycin using a real-world database from a nationwide free web application

IntroductionVancomycin requires a population pharmacokinetic (popPK) model to estimate the area under the concentration-time curve (AUC), and an AUC-guided dosing strategy is necessary. This study aimed to develop a popPK model for vancomycin using a real-world database pooled from a nationwide web application (PAT). MethodsIn this retrospective study, the PAT database between December 14, 2022 and April 6, 2023 was used to develop a popPK model. The model was validated and compared with six existing models based on the predictive performance of datasets from another PAT database and the Kumamoto University Hospital. The developed model determined the dosing strategy for achieving the target AUC. ResultsThe modeling populations consisted of 7146 (13,372 concentrations from the PAT database), 3805 (7540 concentrations from the PAT database), and 783 (1775 concentrations from Kumamoto University Hospital) individuals. A two-compartment popPK model was developed that incorporated creatinine clearance as a covariate for clearance and body weight for central and peripheral volumes of distribution. The validation demonstrated that the popPK model exhibited the smallest mean absolute prediction error of 5.07, outperforming others (ranging from 5.10 to 5.83). The dosing strategies suggested a first dose of 30 mg/kg and maintenance doses adjusted for kidney function and age. ConclusionsThis study demonstrated the updating of PAT through the validation and development of a popPK model using a vast amount of data collected from anonymous PAT users.

Incidence of stroke, subsequent clinical outcomes and health care resource utilization in people with type 2 diabetes: a real-world database study in France: “INSIST” study

BackgroundPeople with type 2 diabetes (T2D) are at elevated risk of cardiovascular disease (CVD) including stroke, yet existing real-world evidence (RWE) on the clinical and economic burden of stroke in this population is limited. The aim of this cohort study was to evaluate the clinical and economic burden of stroke among people with T2D in France.MethodsWe conducted a retrospective RWE study using data from the nationally representative subset of the French Système National des Données de Santé (SNDS) database. We assessed the incidence of stroke requiring hospitalization between 2012 and 2018 among T2D patients. Subsequent clinical outcomes including CVD, stroke recurrence, and mortality were estimated overall and according to stroke subtype (ischemic versus hemorrhagic). We also examined the treatment patterns for glucose-lowering agents and CVD agents, health care resource utilization and medical costs.ResultsAmong 45,331 people with T2D without baseline history of stroke, 2090 (4.6%) had an incident stroke requiring hospitalization. The incidence of ischemic stroke per 1000 person-years was 4.9-times higher than hemorrhagic stroke (6.80 [95% confidence interval (CI) 6.47–7.15] versus 1.38 [1.24–1.54]). During a median follow-up of 2.4 years (interquartile range 0.6; 4.4) from date of index stroke, the rate of CVD, stroke recurrence and mortality per 1000 person-years was higher among hemorrhagic stroke patients than ischemic stroke patients (CVD 130.9 [107.7–159.0] versus 126.4 [117.2–136.4]; stroke recurrence: 86.7 [66.4–113.4] versus 66.5 [59.2–74.6]; mortality 291.5 [259.1–327.9] versus 144.1 [134.3–154.6]). These differences were not statistically significant, except for mortality (adjusted hazard ratio 1.95 [95% CI 1.66–2.92]). The proportion of patients prescribed glucagon-like peptide-1 receptor agonists increased from 4.2% at baseline to 6.6% during follow-up. The proportion of patients prescribed antihypertensives and statins only increased slightly following incident stroke (antihypertensives: 70.9% pre-stroke versus 76.7% post-stroke; statins: 24.1% pre-stroke versus 30.0% post-stroke). Overall, 68.8% of patients had a subsequent hospitalization. Median total medical costs were €12,199 (6846; 22,378).ConclusionsThe high burden of stroke among people with T2D, along with the low proportion of patients receiving recommended treatments as per clinical guidelines, necessitates a strengthened and multidisciplinary approach to the CVD prevention and management in people with T2D.

The impact of expanded access programs for systemic anticancer therapy in an Irish cancer centre

BackgroundExpanded access programs (EAPs) allow cancer patients with unmet clinical need to obtain access to pre-authorisation treatments. There is no standardised process for implementing these programs nationally, and real-world data on their impact is lacking.AimsThis study aimed to evaluate the prevalence of such EAPs and their impact in a cancer centre.MethodsData relating to adult cancer patients treated via EAPs from 2011 to 2021 in three Cork university hospitals was collated. Descriptive statistics were employed to get an overview of the impact these programs currently have on cancer care provision.ResultsWe identified 193 patients who accessed EAPs during the study period, availing of 33 separate drugs for a total of 50 different cancer indications. The prevalence of EAP usage was shown to have been trending upwards in recent years with a total of 189 programs being accessed throughout the period. Drugs provided were from a number of different anti-cancer drug classes, particularly targeted therapies (n = 18) and immune checkpoint inhibitors (n = 17). Cancers from a wide range of both solid and liquid tumour types were treated with EAP drugs, and patients treated were from across a broad spectrum of ages (26–82, SD 11.99).ConclusionsEAPs have an increasing role in accessing novel cancer therapies in our community and by extension nationally. Equity of EAP access would be facilitated by a national registry of available agents which we have established. Assessment of their benefits and toxicities would be enhanced by the requirement for a real-world database as a condition of EAP approval.

Characteristics of patients with Wilson disease in the United States: An insurance claims database study.

Wilson disease (WD) is a progressive, potentially fatal degenerative disease affecting the liver and central nervous system. Given its low prevalence, collecting data on large cohorts of patients with WD is challenging. Comprehensive insurance claims databases provide powerful tools to collect retrospective data on large numbers of patients with rare diseases. To describe patients with WD in the United States, their treatment and clinical outcome, using a large insurance claims database. This retrospective, longitudinal study was performed in the Clarivate Real-World Data Product database. All patients with ≥ 2 claims associated with an International Classification of Diseases 10 (ICD-10) diagnostic code for WD (E83.01) between 2016 and 2021 were included and followed until death or study end. Patients were divided into two groups by whether or not they were documented to have received a specific treatment for WD. Clinical manifestations, hospitalisations, liver transplantation and death were documented. Overall, 5376 patients with an ICD-10 diagnostic code for WD were identified. The mean age at inclusion was 41.2 years and 52.0% were men. A specific WD treatment was documented for 885 patients (15.1%), although the number of patients taking zinc salts may be underestimated due to over the counter purchase. At inclusion, the mean age of patients with a documented treatment was 36.6 ± 17.8 years vs 42.2 ± 19.6 years in those without a documented treatment. During follow-up, 273 patients (5.1%) died. Compared with the American general population, the standardised mortality ratio was 2.19. The proportion of patients with a documented WD-specific treatment who died during follow-up was 4.0% and the mean age at death 52.7 years. Patients treated for WD in the United States had an excess early mortality compared with the American population. These findings indicate that there is a significant unmet need for effective treatment for WD in the United States.

Post-marketing risk analysis of bendamustine: a real-world approach based on the FAERS database.

Objective: Bendamustine was approved for treating chronic lymphocytic leukemia and indolent B-cell non-Hodgkin lymphoma. Despite its therapeutic benefits, the long-term safety of bendamustine in a large population remains inadequately understood. This study evaluates the adverse events (AEs) associated with bendamustine, using a real-world pharmacovigilance database to support its clinical application. Methods: We conducted a post-marketing risk analysis to assess the association between bendamustine and its AEs. Data were extracted from the US FDA's Adverse Event Reporting System (FAERS), covering the period from January 2017 to September 2023. The characteristics of bendamustine-associated AEs and the onset time were further analyzed. Statistical analysis was performed using MYSQL 8.0, Navicat Premium 15, Microsoft EXCEL 2016, and Minitab 21.0. Results: 9,461,874 reports were collected from the FAERS database, 9,131 identified bendamustine as the "primary suspected" drug. We identified 331 significant disproportionality preferred terms (PTs). Common AEs included pyrexia, neutropenia, infusion site reaction, progressive multifocal leukoencephalopathy (PML), injection site vasculitis, and pneumonia-all documented on bendamustine's label. Notably, 16 unexpected and significant AEs were discovered, including hypogammaglobulinemia, which is concerning due to its potential to increase infection susceptibility following bendamustine treatment. Other significant findings were anaphylactic reactions, PML, and cutaneous malignancies, suggesting updates to the drug's label may be necessary. Physicians should monitor for neurological and skin changes in patients and discontinue treatment if PML is suspected. Moreover, the median onset time for bendamustine-associated AEs was 13 days, with an interquartile range [IQR] of 0-59 days, predominantly occurring on the first day post-initiation. The β of bendamustine-related AEs suggested risk reduction over time. Conclusion: Our study uncovered some potential pharmacovigilance signals for bendamustine, providing important insights for its safe and effective clinical use.

The Heidelberg registry of atrial fibrillation. a summary in the era of transition of oral anticoagulation regimes over an 11-year period

Abstract Funding Acknowledgements Type of funding sources: Private company. Main funding source(s): The study was supported by a research grant from Daiichi Sankyo and Bayer diagnostics. The sponsor had no influence on the study concept, data collection, or interpretation. Background Management of patients with atrial fibrillation (AF) has improved in recent years. Particularly, the shift from vitamin-k containing (VKA) oral anticoagulation (OAC) regimes to factor Xa or thrombin inhibitor containing non-vitamin K regimes (NOAC) regimes has revolutionized stroke prevention in AF patients. Purpose This study aimed to illustrate the shift from VKA to NOAC regimes over an 11-year period in an emergency department (ED) setting. Methods The Heidelberg Registry of Atrial Fibrillation (HERA-FIB) is a retrospective, observational single-center study and collected data from patients with AF presenting to the ED of our hospital between 2009 and 2020. Inclusion criteria were (a) diagnosis of AF and (b) age >18 years. Exclusion criteria were (a) non-availability of at least one high sensitive troponin T value and (b) lost to follow-up for all-cause mortality. Repeated visits to the ED were also excluded. Clinical data was accessed retrospectively from available medical records. A sequential follow-up was performed for all-cause mortality, stroke, major bleeding and myocardial infarction. This study was conducted according to ethical principles stated in the Declaration of Helsinki (2008). Results Within the inclusion period of HERA-FIB a total of 76,528 visits to CPU were screened over an 11-year time period. 24.4% were excluded for other diagnosis than AF, resulting in a total of 12,279 visits to ED within the inclusion period. Here, a total of 5.4% of the patients were excluded after re-adjustment of AF diagnosis, 1,5% for non-sufficient laboratory values and 10% for lost-to follow-up. The total study population of HERA-FIB included 10,222 patients with the diagnosis of AF. Within the inclusion period of HERA-FIB, a significant change form VKA containing to NOAC containing anticoagulation regimes could be detected among patients presenting to the ED. Additionally, the number of patients on OAC compared to the number of patients without any OAC regime increased over time. Within the inclusion period, a total of 69.7% received an OAC regime. Here 59.5% of the AF patients received a NOAC and 40.5% VKA at discharge. Hazard ratio for patients on VKA for all-cause mortality was 1.25 (95%CI: 1.11-1.41), p=0.0003. Conclusions HERA-FIB is one of the largest real-world retrospective single-center databases for patients with AF, reflecting the shift from NOAC to VKA containing anticoagulation regimes in AF patients presenting to an ED over an 11-year period.

Proton pump inhibitors are detrimental to overall survival of patients with glioblastoma: Results from a nationwide real-world evidence database

Abstract Background Proton pump inhibitors (PPIs) are often prescribed to manage corticosteroid-induced gastrointestinal toxicity during glioblastoma (GBM) treatment, but were recently identified as strong inducers of aldehyde dehydrogenase-1A1 (ALDH1A1). ALDH1A1 is a primary metabolic enzyme impacting the outcome of chemotherapy, including temozolomide. High expression of ALDH1A1 is associated with poor prognosis in multiple cancers, suggesting PPIs may have a negative impact on survival. Methods Real-world data on GBM patients was annotated from electronic medical records (EMR) according to the prospective observational study, XCELSIOR (NCT03793088). Patients with known IDH1/2 mutations were excluded. Causal effects on survival were analyzed using a multivariate, time-varying Cox Proportional Hazard (CPH) model with stratifications including MGMT methylation status, age, sex, duration of corticosteroid use, extent of resection, starting standard-of-care, and PPI use. Results EMR data from 554 GBM patients across 225 cancer centers was collected, with 72% of patients receiving care from academic medical centers. Patients treated with PPIs (51%) had numerically lower median overall survival (mOS) and 2-year OS rates in the total population and across most strata, with the greatest difference for MGMT-methylated patients (mOS 29.2 vs. 40.1 months). In a time-varying multivariate CPH analysis of the above strata, PPIs caused an adverse effect on survival (HR 1.67 [95% CI: 1.15–2.44], P = .007). Conclusions Evidence from a nationwide cancer registry has suggested PPIs have a negative impact on OS for GBM patients, particularly those with MGMT promoter methylation. This suggests PPIs should be avoided for prophylactic management of gastrointestinal toxicity in patients with GBM receiving chemoradiotherapy.

Clinical outcomes of adjuvant nivolumab in resected stage III melanoma: comparison of CheckMate 238 trial and real-world data

ObjectivesNivolumab is approved as adjuvant therapy for resected stage III/IV melanoma based on the phase 3 CheckMate 238 trial. This analysis compared outcomes from CheckMate 238 with those from the real-world Flatiron Health electronic health record-derived de-identified database in patients with resected stage III melanoma (per AJCC-8) treated with adjuvant nivolumab.MaterialsOutcomes included baseline characteristics, overall survival (OS) in the CheckMate 238 cohort (randomization until death or last known alive), and real-world overall survival (rwOS) in the Flatiron Health cohort (nivolumab initiation until death or data cutoff). rwOS was compared with OS using unadjusted and adjusted Cox proportional hazards models. Inverse probability of treatment weighting (IPTW) was combined with the adjusted model to reduce baseline discrepancies.ResultsThe CheckMate 238 and real-world cohorts included 369 and 452 patients, respectively (median age, 56.0 and 63.0 years; median follow-up, 61.4 vs. 25.5 months). rwOS was not different from OS in the unadjusted (hazard ratio [HR] 1.27; 95% CI 0.92–1.74), adjusted (HR 1.01; 95% CI 0.67–1.54), and adjusted IPTW (HR 1.07; 95% CI 0.70–1.63) analyses. In the adjusted analysis, 2-year OS and rwOS rates were 84%. Median OS and rwOS were not reached. After IPTW, OS and rwOS were not different (HR 1.07; 95% CI 0.70–1.64).ConclusionsIn this comparative analysis, OS in the CheckMate 238 trial was similar to rwOS in the Flatiron Health database after adjustments in patients with resected stage III melanoma (per AJCC-8) treated with adjuvant nivolumab, validating the trial results.

Abstract PO4-01-13: Effect of interruption or discontinuation of endocrine therapy on the prognosis of breast cancer patients: a cohort study using the real-world database

Abstract Background:Adjuvant endocrine therapy is the most important treatment modality as long as one, which can reduce the mortality risk and the recurrence risk for patients with hormone receptor-positive breast cancer. Currently, few studies has reported the association in poor adherence with overall survival(OS) or disease-free-survival(DFS). However, the use of prescription coverage in previous studies to describe patient adherence to endocrine therapy may not be representative of the patient's actual medication. Additionally, previous studies did not distinguish between interruption and discontinuation of endocrine therapy, which is different to clinician. This research used rigorous follow-up data and aims on the effects of discontinuation and interruption on patients with early-stage hormone receptor-positive breast cancer. Methods: Based on the Breast Cancer Information Management System (BCIMS), we identified patients diagnosed with stage I-III breast cancer with hormone receptor-positive and received endocrine therapy during January 1, 1990 to January 1, 2018 in West China Hospital (WCH), Sichuan University, China. Briefly, all patients diagnosed with breast cancer were included and prospectively followed from the diagnosis at WCH or the first visit to WCH for breast cancer. Information, including demographic characteristics, medical history, laboratory results, pathological information, treatments and clinical outcomes, were obtained from clinical records and interviews. Kaplan-Meier analysis, Time-Dependent Cox Regression Model, and subgroup analysis were performed to evaluate the effectiveness of interruption or discontinuation of endocrine therapy. And “X-tile” software is used to select cutoff values in survivorship data. Results:A total of 3,418 eligible patients were included with 8.13(±1.96) years median follow-up. Of these patients, 19.5% did not adhere to standard endocrine regimens, with 6.9% discontinuing and 12.7% discontinuing. The multivariate cox analysis indicates that discontinuation group (DFS:HR=9.71, [95%CI]5.21-18.34,P <0.001; OS:HR=10.41, [95%CI]5.63-19.24,P <0.001) increased the risk of death and breast cancer events compared to the adherence group, but not shown statistical significance difference in the interruption (DFS:HR=1.03,[95%CI]0.23-4.66, P =0.975; OS:HR=1.17, [95%CI]0.26-5.28,P =0.840). We further analyzed the interruption and discontinuation group respectively. In the interruption group, we found cutoff value with 30 months in survival risks but didn't find statistical significance difference in DFS and OS compared to the adherence groups. For the discontinuation group, we divided the patients into low-risk and high-risk groups according to cutoff value (23 months), the final results showed that the high-risk group who took the endocrine therapy less than 23 months had increased the rate of OS(HR=23.98,[95%CI]11.71-49.14, P< 0.001) and DFS(HR=24.03,[95%CI]11.51-50.18, P< 0.001). Conclusion:This study found that interruption of endocrine therapy may not affect prognosis of HR+ breast cancer patients, but prolonged discontinuation increases the risk of relapse and death. Therefore, clinicians should educate patients taking endocrine therapy and encourage those who discontinue the drug to take the drug again as soon as possible. A.Kaplan-Meier Curve for OS B.A.Kaplan-Meier Curve for DFS Kaplan-Meier Curve for OS and DFS in the Interruption Group according to the events location Kaplan-Meier Curve for OS and DFS in the Discontinuation Group according to the total duration of medication Citation Format: Ya Huang, Jie Chen, Yunhao Wu. Effect of interruption or discontinuation of endocrine therapy on the prognosis of breast cancer patients: a cohort study using the real-world database [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO4-01-13.

Abstract PO3-02-02: A prospective, international, observational, real-world evidence database, and collaborative platform for Investigator-Initiated Studies in Early-Stage Breast Cancer tested with MammaPrint and BluePrint– the FLEX Study

Abstract TIPS SABCS 2023 A prospective, international, observational, real-world evidence database, and collaborative platform for Investigator-Initiated Studies in Early-Stage Breast Cancer tested with MammaPrint and BluePrint– the FLEX Study Background: Clinical trials have been an invaluable tool in providing improvements in the discovery, treatment, and quality of life for various diseases and disorders including breast cancer, which impacts millions of people each year. The MammaPrint 70-gene assay along with BluePrint 80-gene subtype analysis are tools to provide such improvements in treatment planning. Historically, patient trial populations have not been racially diverse. Current efforts are focused on improving diversity and inclusion to promote efficacy and health equity across all races/ethnicities. Given recent publications supporting the ability of MammaPrint and BluePrint to identify genomic differences in outcomes of black women with breast cancer, the ongoing multi-center FLEX trial (NCT03053193) has proven to be an unparalleled source for improvement in breast cancer care. With a target of 30,000 enrolled patients, the collaborative research network within FLEX will use MammaPrint, BluePrint, full transcriptome, and clinical data to explore clinical and genomic differences in (sub)populations of interest to promote and advance precision medicine for patients with early-stage breast cancer. Methods: FLEX is the first of its kind to link clinical data with full transcriptome data. It is a prospective, observational trial that enrolls patients who are ≥ 18 years old with histologically proven stage I-III breast cancer with up to 3 positive lymph nodes. Patient eligibility for study enrollment include standard of care MammaPrint testing with or without BluePrint and consent to clinically annotated full transcriptome data collection. The study’s infrastructure facilitates the generation of hypotheses for targeted sub-studies that are important for breast cancer management. The FLEX network fosters collaboration with 99 active sites, including Canada, Greece, and Israel. All proposed substudies are vetted and approved by both internal and external research and scientific review committees. Since launching in April 2017, 13,547 patients have been enrolled including those who have been historically underrepresented in trials (Black n =1032; Latin n= 373; AAPI n =276), 43 investigator initiated sub-studies have been approved and are in progress on a varied number of approaches like MammaPrint/Blueprint clinical utilities, racial disparities, neoadjuvant treatment planning in ER+, and or HER2+ breast cancer with 31 abstracts accepted in national and international congresses. Five ongoing sub-studies within FLEX address differences in underlying biology and treatment response/management among Black, Latina, and Asian American patients with early-stage breast cancer. These studies provide a broader understanding of how differential gene expression patterns, identified with MammaPrint and BluePrint, are unique to racial/ethnic groups and can impact treatment outcomes. Overall, the FLEX study strives to use MammaPrint, BluePrint, and newly developed immune signature, ImPrint, along with full transcriptome data to improve precision medicine in early-stage breast cancer. Citation Format: JJ Alberty-Oller, Lee Riley, Laila Samiian, Sarah Thayer, Olexiy Aseyev, Karen Tedesco, Victoria Poillucci, William Audeh, Danijela Jelovac, Joyce O'Shaughnessy. A prospective, international, observational, real-world evidence database, and collaborative platform for Investigator-Initiated Studies in Early-Stage Breast Cancer tested with MammaPrint and BluePrint– the FLEX Study [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO3-02-02.

Abstract PO4-08-05: Disparities in Genetic Testing Patterns and Positivity Among Patients with Breast Cancer in the CancerLINQ Real-World Oncology Database

Abstract Introduction: Indications for hereditary genetic testing (GT) continue to expand among breast cancer patients (pts), with some guidelines suggesting offering germline GT to all pts diagnosed with breast cancer. The objective of this study was to explore patterns of germline GT and prevalence of pathogenic and likely pathogenic variant (PV) frequency by age, sex, race and ethnicity, and stage at diagnosis within a large, real world oncology database. Methods: The American Clinical Society for Oncology CancerLINQ Discovery breast dataset was used to identify pts with a stage 0-III breast cancer diagnosis who underwent breast surgery at initial diagnosis from 1990-2022. Genetic testing was identified as an available test result from at least one of the following genes: BRCA1/2, ATM, CHEK2, PALB2, TP53, BARD1, BRIP1, CDH1, MHL1, MSH2, MSH6, NF1, RAD51C, or RAD51D. Descriptive statistics were used for comparisons, and adjusted multivariable regression predicting receipt of GT was performed. Results: Overall, 76,978 pts with breast cancer were identified. Of these, 16,284 (21.1%) underwent GT. There were differences in the proportion of pts that underwent GT by age, sex, self-reported race and ethnicity, and stage at diagnosis (Table). Genetic testing decreased with increasing age (59.2% in < 40 vs 7.5% in >=70, p< 0.001) and was more common in men (45.9% vs 21.1% of women, p< 0.001). Genetic testing rates ranged from 18.1-27.7% by race and ethnicity (p< 0.001), with the lowest rates in Non-Hispanic Black (18.1%) and American Indian/Alaskan Native pts (18.2%) and the highest rate in Hispanic pts (27.7%). Genetic testing also differed by stage at diagnosis, with 19.3% of stage I pts vs 25.7% of stage III pts having genetic testing (p< 0.001). On multivariable analysis adjusted for age, sex, race and ethnicity, and stage, male sex was associated with increased likelihood of GT (OR 5.12, 95% CI 4.04-6.49 compared to female sex, p< 0.001) while increasing age (OR 0.05, 95% CI 0.04-0.06 in age >=70 compared to age < 40, p< 0.001) and Non-Hispanic Black or American Indian/Alaskan Native race and ethnicity were associated with decreased likelihood of GT (OR 0.69, 95% CI 0.65-0.73 for Non-Hispanic Black and OR 0.71, 95% CI 0.50-1.00 for American Indian/Alaskan Native pts, compared to Non-Hispanic White pts, p< 0.001); stage was not independently associated with GT. Among those that had GT, PVs were detected in 2,974 (18.3%) pts. PVs were more common in pts < 40 years (27.3% vs 15.0-17.6% in pts >=40, p< 0.001) and in men (26.4% vs 18.2% in women, p< 0.001). Compared by race and ethnicity, PVs were highest among American Indian/Alaskan Native patients (30.2%) and lowest in Non-Hispanic White and Asian/Pacific Islander patients (18.6% and 17.0%, respectively, p< 0.001). There was also a higher prevalence PVs with increasing stage (16.5% for stage 0 and 23.8% for stage III, p< 0.001). Among those with PVs, the distribution was as follows: BRCA1 n=937 (31.5%), BRCA2 n=1176 (39.5%), TP53 n=315 (10.6%), CHEK2 n=238 (8.0%), ATM n=214 (7.2%), and PALB2 n=200 (6.7%). Conclusions: Differences in patterns of GT and PV frequency by age, sex, race and ethnicity, and stage were prevalent. Importantly, despite lower rates of GT, PV frequencies were similar or higher among minority patients and similar among all pts aged 40 and older. Inclusive testing practices and expansion of genetic testing coverage are needed to work towards equitable access to and acceptance of genetic testing. Table. Genetic Testing And Positivity Rates Citation Format: Olga Kantor, Alyssa Jones, Brittany Bychkovsky, Alison Laws, Anna Weiss, Huma Rana, Judy Garber, Rochelle Scheib, Marianna Chavez, Erica Mayer, Tari King, Elizabeth Mittendorf. Disparities in Genetic Testing Patterns and Positivity Among Patients with Breast Cancer in the CancerLINQ Real-World Oncology Database [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO4-08-05.

Abstract PO2-16-05: ESR1 mutations (ESR1mut) in HR(+)HER2(-)patients with metastatic breast cancer (MBC): prevalence along treatment course and predictive value for endocrine therapy (ET) resistance in real-world practice

Abstract Background: ET combined with CDK4/6 inhibitors (CDKi) is the standard of care for HR(+)HER2(-) patients with MBC. ESR1mut is an acquired resistance mechanism to ET, especially aromatase inhibitors (AI). The prevalence and behavior of ESR1mut in patients receiving the selective estrogen receptor degrader (SERD) fulvestrant remains in question. This study aimed to characterize the prevalence of ESR1mut at start of successive lines of therapy and to evaluate clinical outcomes of ET by ESR1 status in 1st line therapy in real-world practice. Methods: This study included patients with HR(+)HER2(-) MBC who underwent genomic testing using Foundation Medicine tissue or liquid comprehensive genomic profiling (CGP) assays, with specimens collected within 60 days of therapy initiation. Patient clinical data was obtained by the nationwide (US-based) de-identified Flatiron Health and Foundation Medicine real-world clinicogenomic breast database (FH-FMI CGDB), originated from ~280 US cancer clinics (~800 sites of care) between 01/2011 and 04/2023. ESR1mut prevalence was calculated in tissue and liquid samples collected in the 1st, 2nd, and 3rd lines of therapy. Real-world progression free-survival (rwPFS), time to treatment discontinuation (rwTTD), and overall survival (rwOS) were compared between patients who received AI + CDKi and between patients receiving fulvestrant + CDKi 1st line therapy [ESR1mut vs. ESR1 wild-type (wt) by tissue CGP] by Cox models. Multivariable analyses adjusted for adjuvant therapy, age, ECOG, menopausal status, histology, stage at diagnosis, metastatic site, and specific ESR1mut (Y537S, D538G, E380W, or others) were performed. Results: The prevalence of ESR1mut in tissue samples collected in 1st, 2nd, and 3rd lines of therapy was 7.9% (n=159/2004), 26.4% (n=66/250), and 34.0% (n=68/200), respectively. The prevalence of ESR1mut in liquid samples collected in the 1st, 2nd, and 3rd lines of therapy was 11.6% (n=30/259) 34.4% (n=63/183), and 35.9% (n=42/117), respectively. Among patients receiving AI + CDKi 1st line therapy (n=485), those with ESR1mut vs. ESR1wt had less favorable rwPFS [median 6.1 vs. 20.8 months, hazard ratio (HR) 2.36, 95% CI 1.35-4.14, p=0.003]. rwTTD and rwOS assessments were consistent with the magnitude of effect of rwPFS. Among patients receiving fulvestrant + CDKi 1st line therapy (n=302), those with ESR1mut vs. ESR1wt had less favorable rwPFS (median 10.5 vs. 14.5 months, HR 1.5, 95% CI 1.05-2.15, p=0.025), but no difference was observed for rwTTD and rwOS (p >0.05). Notably, the multivariable analyses found the independent association of ESR1mut and less favorable rwPFS (HR 2.18, 95% CI 1.15-4.1, p=0.018), rwTTD (HR 3.34, 95% CI, 1.84-6.1, p< 0.001), and rwOS (HR 2.46, 95% CI 1.04-5.9, p=0.041) in patients receiving AI + CDKi. The multivariable analyses confirmed no association between ESR1mut and outcomes in patients receiving fulvestrant + CDKi (p >0.05). No substantial differential associations were observed between specific ESR1mut and clinical outcomes in the multivariable analyses. Conclusion: In our dataset, ESR1mut is prevalent in about 8-11% of baseline tissue and liquid samples of patients with HR(+)HER2(-) MBC. Baseline ESR1mut is associated with less favorable outcomes in patients receiving AI + CDKi 1st line therapy, but not in patients receiving fulvestrant + CDKi. Specific ESR1mut do not seem to be associated with different outcomes to ET. ESR1mut prevalence increased during treatment course. Further investigation is warranted to determine optimal endocrine partner with CDKi based upon ESR1 status, particularly with development of oral SERDs. Citation Format: Manali Bhave, Julia Quintanilha, Ryon Graf, Takara Scott, Hanna Tukachinsky, Gerald Li, Alexa Schrock, Geoffrey Oxnard, Mia Levy, Kevin Kalinsky. ESR1 mutations (ESR1mut) in HR(+)HER2(-)patients with metastatic breast cancer (MBC): prevalence along treatment course and predictive value for endocrine therapy (ET) resistance in real-world practice [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO2-16-05.

Abstract PO2-18-03: Comparison of Provider Adoption of Antibody-Drug Conjugates Among Breast Cancer Patients (pts) and Impact on Duration of Therapy (DOT)

Abstract Background: An assessment was performed to understand the degree of post-approval provider adoption of two antibody-drug conjugates, fam-trastuzumab deruxtecan-nxki (FTD) and sacituzumab govitecan-hziy (SG), to treat breast cancer in the community oncology setting. In addition, an evaluation was performed to assess pt DOT based on the volume of pts on those therapies treated by each provider. In breast cancer, FTD was initially approved in the U.S. on December 20, 2019, and SG was initially approved in the U.S. on April 22, 2020. Methods: This assessment used the Integra Connect PrecisionQ real-world de-identified database of over 2 million cancer pts across 500 sites of care to assess SG and FTD treatment use by provider and DOT for those treated with SG and FTD. It included only breast cancer pts treated with SG or FTD who started after the initial approval dates of the respective therapies. In analyzing the DOT, pts were required to have had a follow-up of 12 months or greater, and only monotherapy treated pts were included to rule out any additional confounders. The FTD pts included were treated between December 2019 to May of 2023, whereas the SG pts included were treated between April 2020 to May 2023. Comparisons of proportions were conducted using a two sample two-tailed z-test and compared median DOT using a Wilcoxon Rank Sum Test. Descriptive analyses were used to summarize pt demographic statistics. Results: 827 pts treated with SG were identified across 376 providers, with an average age at SG treatment start of 60.2 (median of 61); 14% of pts identified as Black or African American and 59% identified as White or Caucasian. Among 827 pts treated with SG across 376 providers, 23% of pts were treated by providers who treated 6 or more pts with SG, which accounted for 6% of all providers. 23% of pts were found to be treated by a provider who used only SG once, which accounted for 56% of all providers. The median DOT among providers who treated 6 or more pts with SG was 168 days (N = 83) compared to 110 days (N = 303) among providers who treated 5 or less pts (p < 0.01). The median DOT for all SG pts was 119 days (N = 386). Of the 1438 pts treated with FTD, the average age at FTD treatment start was 62.1 (median of 63), with 8% of pts identified as Black or African American and 54% identified as White or Caucasian. Among 1438 pts treated with FTD across 485 providers, 38% of pts were treated by providers who treated 6 or more pts with FTD, which accounted for 12% of all providers. 14% of pts were found to be treated by a provider who only used FTD once, which accounted for 40% of all providers. The median DOT among providers who treated 6 or more pts with FTD was 281 days (N = 158) compared to 263 days (N = 234) among providers who treated 5 or less pts (p > 0.05). The median DOT for all FTD pts was 269 days (N = 392). The difference in the number of pts treated by a provider who used SG once (23% of 827 pts) vs. the number of pts treated by a provider who used FTD once (14% of 1438 pts) was found to be statistically significant (p < .01). The difference in pts treated by a provider who used SG in 6 or more pts (23% of 827 pts) vs. compared to providers who used FTD in 6 or more pts (38% of 1438 pts) was found to be statistically significant (p < .01). Conclusion: A large percentage of providers have only used the respective antibody-drug conjugates once (for SG it was 56% of all providers; for FTD 40%), which suggests an opportunity for greater awareness and guidance around effective therapy use and management of antibody-drug conjugates. Providers who used SG more often (6 or more pts) showed a longer DOT for their SG treated pts compared to those providers who used SG in 5 or less pts. This suggests that the slower adoption of SG and lack of experience across the community oncology provider base may be impacting overall pt DOT on SG. Citation Format: Rushir Choksi, Vikram Gorantla, Mike Gart, Simon Blanc, Erin Alwon, Dawn Brenneman, Prateesh Varughese, Justin Scott, Harvey Katzen. Comparison of Provider Adoption of Antibody-Drug Conjugates Among Breast Cancer Patients (pts) and Impact on Duration of Therapy (DOT) [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO2-18-03.

Abstract PO2-18-01: Assessment of Initial Dosing and Dose Management of Sacituzumab Govitecan-hziy (SG) and How Dosing Practices Impact Duration of Therapy (DOT)

Abstract Background: As the Phase 3 ASCENT trial’s safety analysis found that a 10m/kg dose of SG resulted in better efficacy than treatment with a lower dose, this examination sought to use real-world data to evaluate how patients (pts) were dosed compared to the recommended starting dose for SG as well as how the starting dose impacted pt DOT.1 In addition, this assessment sought to understand the rate of dose reductions for pts treated with SG and how the use of dose reductions impacted DOT. Methods: This assessment utilized the Integra Connect PrecisionQ real-world de-identified database of over 2 million cancer pts across 500 sites of care to evaluate starting dose and rate of dose reduction, as well as whether starting dose and use of dose reductions impacted DOT for pts treated with SG. In analyzing the DOT, pts were required to have had a follow-up of 12 months or greater. The SG pt data utilized reflects treatments through May 31, 2023. Comparisons of proportions were conducted using a two sample two-tailed z-test and compared median DOT using a Wilcoxon Rank Sum test. Descriptive analyses were used to summarize pt demographic statistics. Results: 433 pts treated with SG were identified with an average age at treatment start of 59.6 (median of 61); 17% identified as Black or African American and 62% identified as White or Caucasian. Of the 433 pts treated with SG, 83% received the recommended starting dose of 10mg/kg, 13% initiated treatment at 7.5mg/kg and the remaining 5% received 5mg/kg or less. Among the 433 pts, 37% had a dose reduction. The rate of dose reductions for those who started at 10 mg/kg was 35% compared to 43% for pts who started at 7.5mg or less (p >0.05). The rate of dose reductions for those who started on 7.5mg/kg were 39% (N = 57) compared to 55% (N = 18) for those who started on 5mg/kg or less (p >0.05). The median DOT among the pts regardless of starting dose was 116 days (N = 336). The median DOT for pts who started on 10mg/kg was 136 days (N = 254) compared to 77 (N =61) for pts who started on 7.5 mg/kg or less (p = .012). The median DOT for pts who started on 7.5mg/kg was 91 days (N = 166) compared to 58 (N = 17) for those who started on 5mg/kg or less. The median DOT for pts who had a dose reduction was 172 days (N = 125) compared to 89 days (N = 190) for those who did not have a dose reduction (p < 0.001). Conclusion: The assessment found that SG-treated pts who received the recommended starting dose had a longer DOT than those who received a lower starting dose. In addition, dose reductions on SG contributed to a longer time on therapy for pts. These findings suggest using the recommended starting dose for SG and then dose managing via reductions to help keep pts on therapy and delay disease progression. Further evaluation of the impact of starting dose would be needed to understand pt differences in prior lines of therapy and hormonal status to understand how those factors impact DOT. [1] Rugo, H.S., Tolaney, S.M., Loirat, D. et al. Safety analyses from the phase 3 ASCENT trial of sacituzumab govitecan in metastatic triple-negative breast cancer. npj Breast Cancer 8, 98 (2022). https://doi.org/10.1038/s41523-022-00467-1 Citation Format: Vikram Gorantla, Erin Alwon, Mike Gart, John Li, Simon Blanc, Dawn Brenneman, Prateesh Varughese, Justin Scott, Harvey Katzen. Assessment of Initial Dosing and Dose Management of Sacituzumab Govitecan-hziy (SG) and How Dosing Practices Impact Duration of Therapy (DOT) [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO2-18-01.

Abstract PO2-18-02: Utilization of Granulocyte Colony-Stimulating Factor (GCSF) in the Management of Patients (pts) on Sacituzumab Govitecan-hziy (SG) and Impact on Duration of Therapy (DOT)

Abstract Background: An examination was conducted to understand the prevalence of neutropenia in pts managed with SG in the real-world setting, as the ASCENT trial demonstrated a 63% rate of neutropenia in those pts treated with SG1. In addition, an assessment was performed to see whether pts who developed neutropenia on SG received a GCSF and how GCSF use impacted pt DOT on SG. Methods: This assessment utilized the Integra Connect PrecisionQ real-world de-identified database of over 2 million cancer pts across 500 sites of care to evaluate the prevalence of neutropenia (< 1500 neutrophils) among those who were treated with SG, GCSF utilization among those with neutropenia, and the difference in DOT between neutropenic pts who received a GCSF and those who did not. In analyzing the DOT, pts were required to have had a follow-up of 12 months or greater. The SG pts data utilized reflects treatments through May 31, 2023. Comparisons of median DOT were conducted using a Wilcoxon Rank Sum test. Descriptive analyses were used to summarize pt demographic statistics. Results: 447 pts treated with SG were identified with an average age at treatment start of 58.5 (median of 60); 15% identified as Black or African American and 69% identified as White or Caucasian. Of the 447 pts treated with SG, 98% (N = 438) developed neutropenia while on therapy. Among those 438 pts who developed neutropenia, 61% received a GCSF and 39% did not. Of the 330 pts with at least 12 months of follow-up, the median DOT was 119.5 days. Among the 204 pts who received a GCSF, the median DOT was 147 days, compared to a median DOT of 97 days for the 126 pts who did not receive a GCSF (p < 0.001). Conclusion: The DOT for pts treated with SG who received a GCSF was longer than those who did not receive a GCSF while treated with SG. This assessment revealed that approximately 40% of SG treated pts who developed neutropenia did not receive a GCSF. Thus, increasing utilization of GCSFs presents an opportunity to improve management of pts who develop neutropenia while on SG to extend the time on therapy and potentially delay disease progression. These findings warrant further research on the use of prophylactic GCSFs for managing pts who receive SG and suggest further clinical guidance may be needed to provide best practices for managing pts on SG. [1] Rugo, H.S., Tolaney, S.M., Loirat, D. et al. Safety analyses from the phase 3 ASCENT trial of sacituzumab govitecan in metastatic triple-negative breast cancer. npj Breast Cancer 8, 98 (2022). https://doi.org/10.1038/s41523-022-00467-1 Citation Format: Vikram Gorantla, Erin Alwon, Mike Gart, John Li, Simon Blanc, Dawn Brenneman, Emma Genser, Prateesh Varughese, Justin Scott, Harvey Katzen. Utilization of Granulocyte Colony-Stimulating Factor (GCSF) in the Management of Patients (pts) on Sacituzumab Govitecan-hziy (SG) and Impact on Duration of Therapy (DOT) [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO2-18-02.

Abstract PO2-19-07: PROOFS – Pre-/perimenopausal patients with HR+/HER2- EBC with intermediate to high clinical and low genomic risk, treated by endocrine treatment (ET) plus ovarian function suppression (OFS) or chemotherapy followed by ET

Abstract Background During the past years, clinical routine has shifted away from relying solely on clinicopathologic factors toward increasing use of multigene expression assays in guiding treatment decisions regarding adjuvant chemotherapy (CT) for hormone receptor-positive (HR+), HER2-negative (HER2-) early breast cancer (EBC) with 0 to 3 positive lymph nodes. In case of a low genomic risk, there is strong consensus in favor of endocrine treatment (ET) alone for postmenopausal patients, regardless of clinical risk (supported by data from planB, ADAPT, RxPonder, TailorX, MINDACT). However, there is still uncertainty regarding optimal therapy for pre- and perimenopausal patients with a similar clinical/genomic risk profile. Since the observed benefit of CT in this patient group may be partly attributable to CT-induced ovarian function suppression (OFS), some of these patients could be spared CT by adding OFS to endocrine therapy. The West German Study Group (WSG) initiated the PROOFS-registry to create a real-world database on how to optimally treat these patients. Eligibility Criteria PROOFS (NCT05792150) aims at the long-term follow up of pre- or perimenopausal patients with HR+/HER2- EBC with an intermediate to high clinical risk of recurrence and low genomic risk measured by MammaPrint(R). Additional endocrine response assessment (Ki67) after a short preoperative endocrine therapy is encouraged. Up to 25% of the study population may have node-positive disease. Participants undergo standard-of-care treatment at physician´s discretion and according to clinical routine, which may include CT neoadjuvant or adjuvant + ET, ET + OFS in premenopausal, or ET +/- OFS in perimenopausal women. Specific Aims PROOFS aims to give insights in the real-world use of OFS and to confirm an excellent outcome in pre-/perimenopausal women with HR+/HER2- early BC with an intermediate to high clinical risk of recurrence and low genomic risk treated by ET +/- OFS alone (without CT). In addition, quality of life is captured. Statistical Methods The primary objective is to demonstrate the 5-year distant recurrence-free interval (dRFI) in patients treated by ET +/- OFS alone. The null hypothesis H(0) is: 5-year dRFI < 92%. Secondary endpoints for all patients are 5- and 10-year dRFI, distant disease-free survival (dDFS), overall survival (OS), breast cancer-free interval (BCFI), quality of life (QLQ BR23 and QLQ-C30) and therapy adherence. Cox regression models, Kaplan-Meier method and log-rank tests will be applied for survival analysis. Linear mixed models will be utilized to quantitatively describe the course of quality of life-scores as well as therapy adherence, and to conduct group comparisons. Present and Target Accrual The study is open for recruitment of 1500 patients (approximately 20% receiving CT and 80% receiving ET +/- OFS) at up to 100 centers in Germany (June 2023: 24 open for recruitment). Funding AGENDIA N.V., Amsterdam Contact Information rachel.wuerstlein@med.uni-muenchen.de Citation Format: Rachel Wuerstlein, Lotta Ada Fischer, Nadia Harbeck, Monika Graeser, Ulrike Nitz, Matthias Christgen, Sherko Kuemmel, Christine zu Eulenburg, Matthias Warm, Oleg Gluz. PROOFS – Pre-/perimenopausal patients with HR+/HER2- EBC with intermediate to high clinical and low genomic risk, treated by endocrine treatment (ET) plus ovarian function suppression (OFS) or chemotherapy followed by ET [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO2-19-07.