AbstractPurpose: The EMERALD trial led to the approval of elacestrant for estrogen receptor (ER)–positive, HER2-negative, estrogen receptor 1 (ESR1)–mutated advanced or metastatic breast cancer (mBC) with disease progression following at least one line of endocrine therapy (ET). Subgroup analyses provided evidence suggesting that elacestrant enables ET sequencing in the second line before other targeted combinations, which could delay chemotherapy-based regimens. Experimental Design: This study used claims data from the Komodo Research Dataset linked with Foundation Medicine Inc. clinical genomic data from patients with estrogen receptor+/HER2− mBC harboring an ESR1 mutation treated with elacestrant. The primary outcome measure was time to next treatment (TTNT). Results: Among 306 patients, 93.8% had prior ET ± cyclin-dependent kinase 4/6 inhibitor for ≥12 months, 50.0% had prior chemotherapy, and 72.2% had prior fulvestrant. Median TTNT (mTTNT) was 8.2 months [95% confidence interval (CI), 6.3–13.0] in patients with 1 to 2 prior lines and 7.5 months (95% CI, 7.1–9.9) in those with ≥3 prior lines of ET. In patients with coexisting ESR1- and PI3K-pathway–mutated tumors, mTTNT was 6.3 months (95% CI, 4.8–7.9). mTTNT was 7.9 months (95% CI, 7.1–9.8) in all patients and was also sustained in patients with no prior fulvestrant [12.9 months (95% CI, 7.2–not reached)], no prior chemotherapy [8.4 months (95% CI, 7.1–13.3)], visceral metastasis [7.9 months (95% CI, 7.0–9.9)], and liver metastases [7.2 months (95% CI, 6.3–9.0)]. Conclusions: Elacestrant demonstrated a durable benefit in real-world clinical practice, particularly in earlier lines and in patients with prolonged prior ET exposure. Despite coexisting ESR1 and PI3K pathway mutations, TTNT remained clinically meaningful, reinforcing the role of elacestrant in personalized ET sequencing strategies prior to chemotherapy, antibody–drug conjugates, or targeted combinations. See related article by Lloyd et al., p. 169

PURPOSE:The EMERALD trial led to the approval of elacestrant for estrogen receptor (ER)-positive, HER2-negative, estrogen receptor 1 (ESR1)-mutated advanced or metastatic breast cancer (mBC) with disease progression following at least one line of endocrine therapy (ET). Subgroup analyses provided evidence suggesting that elacestrant enables ET sequencing in the second line before other targeted combinations, which could delay chemotherapy-based regimens. EXPERIMENTAL DESIGN:This study used claims data from the Komodo Research Dataset linked with Foundation Medicine Inc. clinical genomic data from patients with estrogen receptor+/HER2- mBC harboring an ESR1 mutation treated with elacestrant. The primary outcome measure was time to next treatment (TTNT). RESULTS:Among 306 patients, 93.8% had prior ET ± cyclin-dependent kinase 4/6 inhibitor for ≥12 months, 50.0% had prior chemotherapy, and 72.2% had prior fulvestrant. Median TTNT (mTTNT) was 8.2 months [95% confidence interval (CI), 6.3-13.0] in patients with 1 to 2 prior lines and 7.5 months (95% CI, 7.1-9.9) in those with ≥3 prior lines of ET. In patients with coexisting ESR1- and PI3K-pathway-mutated tumors, mTTNT was 6.3 months (95% CI, 4.8-7.9). mTTNT was 7.9 months (95% CI, 7.1-9.8) in all patients and was also sustained in patients with no prior fulvestrant [12.9 months (95% CI, 7.2-not reached)], no prior chemotherapy [8.4 months (95% CI, 7.1-13.3)], visceral metastasis [7.9 months (95% CI, 7.0-9.9)], and liver metastases [7.2 months (95% CI, 6.3-9.0)]. CONCLUSIONS:Elacestrant demonstrated a durable benefit in real-world clinical practice, particularly in earlier lines and in patients with prolonged prior ET exposure. Despite coexisting ESR1 and PI3K pathway mutations, TTNT remained clinically meaningful, reinforcing the role of elacestrant in personalized ET sequencing strategies prior to chemotherapy, antibody-drug conjugates, or targeted combinations. See related article by Lloyd et al., p. 169.

mTTNT benefit in relevant subgroups.

The REAL-AVA 2.0 study was a retrospective multisite chart review evaluating avatrombopag (AVA) effectiveness among patients with primary immune thrombocytopenia (ITP) who underwent routine care in academic- and community-based practices in the United States and initiated AVA between 1 July 2019 and 30 June 2024. Treatment response was defined as achieving platelet counts (PC) ≥30 × 103/μL, ≥50 × 103/μL, or ≥100 × 103/μL. The discontinuation of steroids and/or immunosuppressants after AVA initiation was evaluated. Analyses were performed in the overall population and among 2 stratified subgroups: ITP disease duration (acute, <3 months; persistent, 3-12 months; and chronic, ≥12 months) and prior thrombopoietin receptor agonists exposure status. Among the 177 patients included in the study, 90% achieved or maintained a PC ≥30 × 103/μL response, 86% achieved or maintained a PC ≥50 × 103/μL response, and 76% of patients achieved or maintained a PC ≥100 × 103/μL response, with a median duration of response to AVA of 12.1, 12.4, and 10.0 months, respectively. The median durability of response was 96% at the PC ≥30 × 103/μL threshold, 93% at the PC ≥50 × 103/μL threshold, and 76% at the PC ≥100 × 103/μL threshold. Almost all patients (98%) who used concomitant steroids at AVA initiation subsequently reduced the steroid dose (19%) or discontinued steroid use completely (79%), and 40% of those who used immunosuppressants discontinued them after AVA initiation. Results of the subgroup analyses were consistent with the overall sample. Findings show that AVA is an effective treatment option for patients with ITP, demonstrating durable PC response in a diverse population.

Thrombopoietin receptor agonists (TPO-RAs), including eltrombopag (ELT), romiplostim (ROMI), and avatrombopag (AVA), are United States Food and Drug Administration (FDA)-approved treatments for chronic immune thrombocytopenia (ITP), an autoimmune disorder characterized by low platelet counts (PCs) and risk of severe bleeding. TPO-RA treatments aim to raise PCs above targeted thresholds. Prior research has found that switching TPO-RAs because of tolerability, adherence, or convenience reasons can improve PC response. This study aimed to assess TPO-RA switches and treatment response among patients who used ELT or ROMI before initiating AVA using real-world data.

KEY POINTS:Patients with nondiabetic apolipoprotein L1-mediated kidney disease progressed to dialysis and transplant faster than patients with other forms of nondiabetic CKD. Although patients with apolipoprotein L1-mediated kidney disease were younger with fewer comorbidities, kidney decline was accelerated underscoring the aggressive nature of apolipoprotein L1-mediated kidney disease. These findings highlight the need of targeted therapies for apolipoprotein L1-mediated kidney disease and earlier identification through genetic testing to improve patient outcomes. BACKGROUND:Apolipoprotein L1-mediated kidney disease (AMKD) is an aggressive form of CKD. This study described characteristics of nondiabetic patients with AMKD and compared their disease progression with nondiabetic patients with other forms of CKD. METHODS:This retrospective study used clinical and biosample data from NashBio (NashBio contains electronic health records generated during clinical encounters at Vanderbilt University Medical Center). Nondiabetic patients with ≥1 CKD diagnosis code who were 10 years or older at index (date of first CKD diagnosis code in patient's medical record) were included. The AMKD and other forms of CKD cohorts were defined on the basis of the presence of apolipoprotein L1 risk alleles, and then their clinical and demographic characteristics were described. To assess progression patients were matched 1:1 on sex, presence of hypertension, and CKD stage at index and were followed until the last observation in the data. Progression outcomes including time from index to dialysis, kidney transplant, and diagnosis of CKD requiring KRT were assessed using Kaplan-Meier analysis, with log-rank tests used to compare matched cohorts. RESULTS:The study included 645 patients with AMKD and 6749 patients with other forms of CKD. Patients with AMKD were significantly younger than patients with other CKD (median 44.0 versus 61.0 years; P < 0.001) and had significantly less comorbidity burden such as cardiovascular diseases (16.9% versus 36.6% P < 0.001). In addition, patients with AMKD had higher rates of CKD requiring KRT at index (59% versus 24%, P < 0.001). After 1:1 matching, patients with AMKD reached dialysis and kidney transplant significantly faster than patients with other CKD (both P < 0.001). Among patients who did not require KRT at index ( n =264 per cohort), patients with AMKD progressed to CKD requiring KRT significantly faster than patients with other CKD ( P < 0.01). CONCLUSIONS:Nondiabetic patients with AMKD experienced more rapid disease progression than patients with other forms of CKD, despite being younger and having lower comorbidity burden.

Median efficacy outcomes of elacestrant in three analyses.

Overall demographics and clinical characteristics.

Apolipoprotein L1 ( APOL1 )-mediated kidney disease (AMKD) is an aggressive form of chronic kidney disease (CKD). This study described characteristics of non-diabetic patients with AMKD and compared their disease progression to non-diabetic patients with other forms of CKD. This retrospective study used clinical and biosample data from NashBio (Nashbio contains electronic health records (EHR) generated during clinical encounters at Vanderbilt University Medical Center (VUMC)). Non-diabetic patients with ≥ 1 CKD diagnosis code who were ≥10 years of age at index (date of first CKD diagnosis code in patient’s medical record) were included. The AMKD and other forms of CKD cohorts were defined based on the presence of APOL1 risk alleles and then their clinical and demographic characteristics were described. To assess progression patients were matched 1:1 on gender, presence of hypertension, and CKD stage at index and were followed until the last observation in the data. Progression outcomes including time from index to dialysis, kidney transplant, and diagnosis of CKD requiring kidney replacement therapy were assessed using Kaplan-Meier analysis, with log-rank tests used to compare matched cohorts. The study included 645 patients with AMKD and 6,749 patients with other forms of CKD. AMKD patients were significantly younger than other CKD patients (median 44.0 vs. 61.0 years; p<0.001) and had significantly less comorbidity burden such as cardiovascular diseases (16.9% versus 36.6% p < 0.001). Additionally, AMKD patients had higher rates of CKD requiring kidney replacement therapy at index (59% vs. 24%, p<0.001). After 1:1 matching, AMKD patients reached dialysis and kidney transplant significantly faster than other CKD patients (both p<0.001). Among patients who did not require kidney replacement therapy at index (n=264 per cohort), AMKD patients progressed to CKD requiring kidney replacement therapy significantly faster than other CKD patients (p<0.01). Non-diabetic patients with AMKD experienced more rapid disease progression than patients with other forms of CKD, despite being younger and having lower comorbidity burden.

Immune thrombocytopenia (ITP) is an autoimmune disorder characterized by low platelet counts (PCs) and increased bleeding risk.Thrombopoietin receptor agonists (TPO-RA) aim to increase PCs to target levels to minimize this risk. ITP duration can be classified as acute (< 3 months), persistent (3-12 months) or chronic (≥1 year). Avatrombopag (AVA) is a TPO-RA that gained FDA approval for the treatment of adults with chronic ITP in 2019, but realworld data have also shown its use in acute and persistent ITP. The objective of this study is to describe response to AVA among patients with chronic and acute/persistent ITP.

Background: Endocrine therapy (ET) + CDK4/6i is the standard-of-care (SOC) for 1st-line treatment of ER+/HER2- advanced or metastatic breast cancer (mBC). In current practice, sequential endocrine monotherapy or combination therapies are used in the 2nd-line post ET+CDK4/6i as recommended by guidelines. Combination regimens in ≥2nd-line mBC can be associated with significant toxicities and high discontinuation rates. ESR1 mutations represent a type of acquired resistance that eventually emerges in up to 50% of patients during ET for ER+/HER2- mBC. The EMERALD trial (NCT03778931) demonstrated median PFS of 3.8 months for elacestrant vs 1.9 months for SOC ET (HR = 0.55; 95% CI, 0.39-0.77; P = 0.0005) with manageable safety in patients with ER+/HER2- mBC and ESR1-mutated tumors previously treated with ET+CDK4/6i (Bidard, 2022). Elacestrant is the first and only oral SERD approved targeting ESR1-mutated tumors. Sufficient time has passed since approval in January 2023 to characterize the real-world use of elacestrant in the current treatment landscape. This study aims to describe the rwPFS of patients who received elacestrant after Food and Drug Administration (FDA) approval in the United States. Methods: Adults with newly diagnosed ER+/HER2- mBC who initiated elacestrant in a real-world setting between January 2023 and December 2023 were identified in the Komodo Research Database (KRD+). Demographic information was described at the time of first administration of elacestrant (index date); metastatic sites were identified during the 6-month baseline period prior to the index date; and prior treatments received in the mBC setting were described among patients with sufficient health plan enrollment between the first observed mBC diagnosis and the index date. rwPFS, defined as time from index date until the earliest outcome (start of the next line of therapy or death), was assessed using time-to-event and Kaplan-Meier methods. Patients were censored at the first occurrence of the following: discontinuation of all therapy, end of data availability, or end of health plan enrollment. Elacestrant is indicated for the treatment of postmenopausal women or adult men with ER+/HER2- ESR1-mutated advanced or mBC with disease progression following at least one line of ET. ESR1-mutation status was not available in the database at the time of analysis. Results: A total of 212 patients treated with elacestrant with sufficient health plan enrollment were evaluated (median age was 63 years, 97% were female). Prior to initiating elacestrant, 89% of patients received prior treatment with a CDK4/6i, 58% were treated with only 1-2 prior lines of ET in the metastatic setting, and 62% had visceral metastases. The median follow-up time was 5.2 months. In the overall population analysis, median rwPFS (95% CI) was 6.8 months (5.4-not reached [NR]). Median rwPFS for patients with 1-2 lines of prior ET in mBC was 8 months (4.9-NR), and median rwPFS for patients with visceral metastases was 6.1 months (4.7-NR). Updated results and additional information will be presented based on longer follow-up. Conclusion: This retrospective observational study expands our understanding of elacestrant’s activity in ER+/HER2- mBC patients with prior exposure to ET in a real-world setting. Citation Format: Elyse Swallow, Jessica Maitland, Kirthana Sarathy, Ellen Sears, Yasir Nagarwala, Janelle DePalantino, Eric Kruep, Corey Pelletier, Sebastian Kloss, Tomer Wasserman. Elacestrant real-world progression-free survival (rwPFS) of adult patients with ER+/HER2-, advanced breast cancer: a retrospective analysis using insurance claims in the United States [abstract]. In: Proceedings of the San Antonio Breast Cancer Symposium 2024; 2024 Dec 10-13; San Antonio, TX. Philadelphia (PA): AACR; Clin Cancer Res 2025;31(12 Suppl):Abstract nr P3-10-08.

•IV protein C concentrate (Ceprotin®) treatment is approved for patients with SCPCD.•Data on the real-world use of protein C concentrate are limited.•An online physician survey provides insights into real-world clinical practice.•Both IV and SC long-term prophylaxis were reported in clinical practice.•Physicians are interested in the SC route of administration being approved.

Background: Several oral disease-modifying therapies (DMTs) have been approved by the Food and Drug Administration for the treatment of relapsing-remitting multiple sclerosis (RRMS). In the absence of head-to-head randomized data, matching-adjusted indirect comparisons (MAICs) can evaluate the comparative effectiveness and safety of ozanimod versus other oral DMTs in RRMS. Objectives: To synthesize results from the published MAICs of ozanimod and other oral DMTs for 2-year outcomes in RRMS. Methods: Published MAICs involving ozanimod for the treatment of RRMS were identified. Extracted data elements included efficacy [annualized relapse rate (ARR), confirmed disability progression (CDP), and brain volume loss] and safety [adverse events (AEs), serious AEs (SAEs), AEs leading to discontinuation, and infection] outcomes. Results: The four MAIC studies identified compared ozanimod with fingolimod, teriflunomide, dimethyl fumarate (DMF), and ponesimod. All comparisons were adjusted for differences in age, sex, relapses within the previous year, Expanded Disability Status Scale score, and percentage of patients with prior DMTs. Outcomes at 2 years were analyzed based on comparisons that lacked a common comparator arm. Ozanimod was associated with significantly lower ARR versus teriflunomide [ARR ratio (95% CI) 0.73 (0.62, 0.84) and DMF 0.80 (0.67, 0.97)], with no significant difference versus fingolimod or ponesimod. The proportions of patients treated with ozanimod or fingolimod had similar 3- and 6-month CDP. Compared with teriflunomide and DMF, ozanimod was associated with a significantly lower risk of 3-month CDP; 6-month CDP was comparable. Ozanimod was associated with significantly lower rates of any AE and AEs leading to discontinuation compared with the other oral DMTs evaluated. Ozanimod also had significantly lower rates of SAEs versus teriflunomide and DMF and lower rates of reported infection outcomes versus fingolimod and ponesimod. Conclusion: Compared with the other oral DMTs evaluated in MAICs, ozanimod was associated with a favorable safety profile and improved or comparable efficacy outcomes. Keywords fingolimod , matching-adjusted indirect comparison , ozanimod , ponesimod , relapsing-remitting multiple sclerosis , teriflunomide

Background: Several oral disease-modifying therapies (DMTs) have been approved by the Food and Drug Administration for the treatment of relapsing-remitting multiple sclerosis (RRMS). In the absence of head-to-head randomized data, matching-adjusted indirect comparisons (MAICs) can evaluate the comparative effectiveness and safety of ozanimod versus other oral DMTs in RRMS. Objectives: To synthesize results from the published MAICs of ozanimod and other oral DMTs for 2-year outcomes in RRMS. Methods: Published MAICs involving ozanimod for the treatment of RRMS were identified. Extracted data elements included efficacy [annualized relapse rate (ARR), confirmed disability progression (CDP), and brain volume loss] and safety [adverse events (AEs), serious AEs (SAEs), AEs leading to discontinuation, and infection] outcomes. Results: The four MAIC studies identified compared ozanimod with fingolimod, teriflunomide, dimethyl fumarate (DMF), and ponesimod. All comparisons were adjusted for differences in age, sex, relapses within the previous year, Expanded Disability Status Scale score, and percentage of patients with prior DMTs. Outcomes at 2 years were analyzed based on comparisons that lacked a common comparator arm. Ozanimod was associated with significantly lower ARR versus teriflunomide [ARR ratio (95% CI) 0.73 (0.62, 0.84) and DMF 0.80 (0.67, 0.97)], with no significant difference versus fingolimod or ponesimod. The proportions of patients treated with ozanimod or fingolimod had similar 3- and 6-month CDP. Compared with teriflunomide and DMF, ozanimod was associated with a significantly lower risk of 3-month CDP; 6-month CDP was comparable. Ozanimod was associated with significantly lower rates of any AE and AEs leading to discontinuation compared with the other oral DMTs evaluated. Ozanimod also had significantly lower rates of SAEs versus teriflunomide and DMF and lower rates of reported infection outcomes versus fingolimod and ponesimod. Conclusion: Compared with the other oral DMTs evaluated in MAICs, ozanimod was associated with a favorable safety profile and improved or comparable efficacy outcomes.