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Effects of tai chi qigong on gene expression profiles in older male cancer survivors with fatigue.
12038 Background: The HERO trial showed that Tai Chi Qigong (TCQ) reduced fatigue (primary endpoint) in male cancer survivors. Fatigue-related biological pathways influenced by mind-body therapies, such as TCQ, remain poorly defined. This trial hypothesized that TCQ, compared to an exercise-intensity matched (EIM) intervention and usual care (UC), would have a more favorable effect on the regulation of two major fatigue-associated functional gene clusters: a) inflammation-vasodilation-metabolite sensing and b) energy and adrenergic activation among older male cancer survivors with fatigue. Methods: In this three-arm randomized trial (NCT 03345563), 113 male cancer survivors aged ≥ 55 years with fatigue were randomized to 12 weeks of TCQ (n = 45), EIM (n = 43), or UC (n = 25), delivered twice weekly with recommended home practice. Gene expression profiles were assessed at baseline and at 1 week and 3 months post-intervention using genome-wide transcriptional profiling of blood samples. A key secondary endpoint was changes in gene expression at the 3-month follow-up. A minimum of 8 subjects per study arm is required to achieve 80% power (two-sided alpha = 0.05) to detect a 2.0-fold change in gene expression. Intervention effects were evaluated using an intention-to-treat approach and general mixed linear models, with baseline adjustment and time of sample collection included as time-varying covariates. Multiple comparisons were controlled for using the false discovery rate (FDR). Upregulation of DBI, IL-10, ADRB2, VIPR2, OXTR, ASIC3, P2RX4, P2RX7, ATP5E, NDUFS5 genes and downregulation of TNF, NR3C1, P2RY1, HSPA2 genes were deemed as favorable effects. Mean difference (MD), 95% CI, and FDR corrected p-values were reported. Results: TCQ favorably regulated the expression of genes associated with inflammation (TNF: MD = -1.25; CI: -1.97 – -0.53; p = 0.001 and IL-10: MD = 0.51; CI: 0.02 – 1.00; p = 0.043), metabolite-sensing (P2RX4: MD = 0.45; CI: 0.04 – 0.85; p = 0.032), and energy activation (P2RY1: MD = -0.43; CI: -0.95 – -0.08; p = 0.037, ATP5E: MD = 0.15; CI: 0.05 – 0.30; p = 0.035, and NDUFS5: MD = 0.14; CI: 0.02 – 0.28; p = 0.042) at 3 months post-intervention. EIM favorably regulated genes associated with vasodilation (OXTR: MD = 0.89; CI: 0.36 – 1.42; p = 0.001) and inflammation (NR3C1: MD = -0.24; CI: -0.47 – -0.01; p = 0.043). Compared with EIM, TCQ produced greater increases in ADRB2, an adrenergic activator (MD:0.81; CI: 0.26 – 1.35; p = 0.003) and P2RX4 (MD:0.56; CI: 0.12 – 1.01; p = 0.013) and favorably decreased the expression of P2RY1 (MD:-0.93; CI: -1.51 – -0.35; p = 0.002). Conclusions: TCQ produced meaningful changes in inflammatory, adrenergic, energy, and metabolic pathways, supporting potential biological mechanisms through which TCQ may reduce fatigue in older male cancer survivors. Larger trials with a broader representation of participants are needed to confirm these pathway-level effects. Clinical trial information: NCT03345563 .
Trends in frontline treatment patterns for multiple myeloma among US veterans, 1999–2025.
7576 Background: Frontline treatment for multiple myeloma (MM) has evolved substantially, transitioning from alkylating therapy to newer therapeutic classes, including immunomodulatory drugs, proteasome inhibitors, and monoclonal antibodies. Despite these advances, real-world treatment patterns remain heterogeneous, and MM therapies carry substantial toxicity and costs. Using nationwide Veterans Health Administration (VHA) data, an integrated health system with longitudinal follow-up, we characterized frontline treatment patterns for MM among US Veterans from 1999 to 2025. Methods: We identified Veterans diagnosed with MM in the VHA from 1999 to 2025. Diagnoses were confirmed using a published and validated natural language processing (NLP) algorithm, with the index date defined as the first MM-specific treatment, excluding dexamethasone alone. Patients receiving no MM-specific therapy or dexamethasone alone were excluded. Frontline treatments were defined as treatments initiated within 30 days of the index date. Treatments were captured using VA inpatient and outpatient pharmacy files, inpatient and outpatient procedure records for injectable agents, Fee Basis and Community Care data, and CMS Medicare Part D claims. Because the VHA does not require insurance approval, a 30-day window was used to define frontline treatment. Hematopoietic stem cell transplant was excluded to focus on trends in frontline treatments. MM-specific treatments were defined using a clinician-reviewed list of medications and relevant Current Procedural Terminology (CPT) codes. Results: We identified 4,738 Veterans with MM from 1999 to 2025. Median age was 72.1 years (IQR 65.1-78.1), and 96.7% were men. Non-Hispanic Black accounted for 20.1%, non-Hispanic White 55.6%, Hispanic 3.0%, and other races 1.5%. Median BMI was 27.6 (IQR 24.3-31.8), and 63.3% lived in urban areas. Melphalan predominated in 1999 (85.3%) but steadily declined. Cyclophosphamide use increased from 10.5% in 1999 to a peak of 29.2% in 2015, followed by a decline to 10.4% in 2024. Thalidomide use peaked in 2005 (61.8%) and declined to near zero by 2017. Lenalidomide use increased after 2006, reaching 78.1% in 2024. Bortezomib increased from 1.2% in 2004, peaking at 49.4% in 2015 and remaining common, whereas carfilzomib and ixazomib were infrequently used ( < 6%). Monoclonal antibody use expanded after 2019 with daratumumab, reaching 45.5% in 2024. Conclusions: Using national VHA data from 1999 to 2025, we describe real-world frontline MM treatment patterns among US Veterans, illustrating temporal shifts in therapeutic class use, including increasing adoption of monoclonal antibodies within an integrated, longitudinal health system.
Advancing HER2 testing and evidence-based treatment in non–small cell lung cancer: A quality improvement initiative across academic and community settings.
e23309 Background: Treatment recommendations for biomarker-directed therapy in advanced non-small cell lung cancer (NSCLC) are rapidly evolving, with current clinical guidelines recommending assessment of both HER2 overexpression (OE) and HER2 gene mutations. However, integrating HER2 testing into practice remains a significant challenge. To address this, we implemented a data-driven quality improvement (QI) initiative to evaluate current practices and identify opportunities to optimize HER2 testing and evidence-based care. Methods: Between August–October 2025, healthcare professionals at two academic cancer centers (aHCPs; n = 65) completed surveys and baseline patient chart audits (n = 75) to identify practice gaps. At audit-feedback (AF) sessions, aHCPs reviewed site-specific findings from the baseline assessment and developed action plans to address identified gaps, including integrating a HER2 testing resource into practice. In parallel, a nationwide survey of community HCPs (cHCPs; n = 72) was conducted to evaluate real-world practice patterns and benchmark community care against academic centers. Results: Routine assessment of HER2 was inconsistent across settings. Assessment of HER2 mutations for every patient was reported by 29% of aHCPs and 18% of cHCPs and assessment of overexpression for every patient was reported by 31% and 18%, respectively. Chart audits revealed HER2 testing was ordered on pathology requisition in 51% of cases. Among tested patients, 82% received NGS testing for mutations, while only 13% received testing by IHC for OE. Major barriers to HER2 OE testing included executing the ordering for the test (aHCPs/cHCPs: 42%/32%), limited access to testing facilities/equipment (31%/39%), and communication and/or coordination between oncology and pathology (34%/32%). Key strategies identified for improving HER2 OE testing included institutional support for reflex testing protocols (65%/49%), better electronic health record (EHR) integration with pathology (57%/53%), and integrating training or education sessions (20%/42%). Additionally, HCPs reported that shared EHR (42%/51%), reflex testing protocols (37%/47%), and dedicated liaisons or navigators (39%/28%) would most improve collaboration between oncology and pathology. Academic AF sessions resulted in action plans focused on standardizing HER2 testing protocols, enhancing multidisciplinary communication, and securing leadership support for integrated testing workflows. Conclusions: Significant gaps exist in HER2 testing in academic and community oncology settings. Targeted QI interventions addressing workflow inefficiencies, multidisciplinary coordination, and institutional infrastructure may improve implementation of comprehensive HER2 testing and delivery of evidence-based care for patients with advanced NSCLC.
Impact of reflexive next-generation sequencing on treatment initiation in non–small cell lung cancer.
e20096 Background: Timely identification of actionable mutations is critical for guiding targeted therapy and immunotherapy in non-small cell lung cancer (NSCLC). In previous work, our group has shown that reflexive next generation sequencing (NGS), where molecular testing is initiated by pathology at the time of diagnosis, resulted in a 40.6% reduction in NGS reporting time. In this retrospective study, we investigated whether these improvements were associated with improvements in diagnostic to treatment timelines and downstream clinical care metrics among patients with NSCLC. Methods: We conducted a retrospective cohort study of patients diagnosed with NSCLC who underwent NGS testing during their diagnostic evaluation (N = 49). Time zero was defined as the specimen collection date from biopsy/surgical resection to initiation of treatment. We used Foundation One Companion Diagnostic (CDx) to identify tumor mutation profiles to detect biomarkers with FDA-approved targeted therapies. Patients who did not undergo oncology evaluation or who had insufficient clinical data due to early death were excluded. Key intervals consisted of biopsy to finalized NGS report and biopsy to treatment initiation. Continuous variables were summarized using medians and interquartile ranges (IQRs) and compared using Mann-Whitney U tests. Categorical variables were compared using Fisher’s exact test. Results: A total of 42 patients with NSCLC were included in the analysis, including 22 patients in the non-reflexive NGS cohort and 20 patients in the reflexive NGS cohort. The median age at diagnosis was 69.5 years [range 32-85]. Most patients presented with advanced-stage disease, with stage IV disease in 27 patients (64.2%), stage III in 9 patients (21.4%), and early-stage disease (stage I-II) in 6 patients (14.2%). Among patients with systemic therapy treatments, reflexive testing was associated with a shorter time from biopsy to treatment initiation (median 34.0 days [IQR 31.0-36.5] vs 51.5 days [IQR 38.5-63.5], p = 0.009). Molecular profiling results were available prior to initiation of first-line therapy in 100% of patients in the reflexive group compared with 83.3% in the non-reflexive group. Acute care visits and hospitalizations did not differ significantly between reflexive and non-reflexive cohorts, although a nonsignificant trend toward fewer acute care visits was observed in the reflexive group. Conclusions: Reflexive NGS implementation was associated with a significantly shorter diagnosis to treatment timeline and implement in molecular readiness at the time of treatment initiation. These improvements showed a significant reduction in time to initiation of appropriate and specific systemic therapy. These findings support reflexive molecular testing as a pragmatic, system level intervention to improve quality care by accelerating appropriate treatment decisions and care delivery in NSCLC.
Non-invasive MRD monitoring and profiling of clonal evolution by ctDNA in patients with advanced cancers treated within molecular tumor boards.
3041 Background: Profiling of targetable genetic alterations within molecular tumor boards (MTB) guides for personalized treatment selection in patients with advanced cancers. During therapy, response is typically assessed by CT scans or MRI, which often have suboptimal sensitivity and specificity. Circulating tumor DNA (ctDNA) from blood plasma has emerged as a promising biomarker for noninvasive profiling of tumor mutational landscapes and disease monitoring. Here, we applied a pan-cancer next-generation sequencing (NGS) technology to assess the role of ctDNA for comprehensive tumor genotyping, early response prediction, and characterization clonal heterogeneity in patients receiving MTB recommended therapies. Methods: We developed and applied a custom targeted NGS approach (ExTARGET), which covers 266 genes across a 540 kb genomic region, to 157 plasma samples obtained at distinct milestones from 57 patients with diverse solid cancers. Plasma samples from healthy individuals ( n = 24) were used to determine the specificity of our technology. Results: We identified variants in 96% of baseline plasma samples by ctDNA profiling, with a median of 7 mutations per patient (range: 1-41). Most frequently mutated genes included KRAS (35%), BRAF (24%), ERBB2 (22%) and TP53 (22%). Targetable tumor variants that led to treatment recommendations within the MTB were found non-invasively in 69% of patients. Longitudinal monitoring of baseline ctDNA variants in on-treatment samples, obtained early during therapy ( n = 21), revealed that ctDNA dynamics were predictive of disease progression and preceded radiological/clinical progression in 8/19 (42%) patients. All patients with increasing ctDNA levels early during treatment showed radiologic disease progression in subsequent CT scans. On the other hand, an early decrease of ctDNA levels was associated with durable disease control in most patients and significantly favorable progression-free survival ( p = 0.008; HR = 0.1, 95%CI: 0.02-0.6). Next, we explored temporal clonal heterogeneity in plasma samples collected from 16 patients with disease progression following MTB-recommended therapies. We observed substantial clonal evolution over time, with all samples harboring at least one emerging variant. Among these emerging alterations, 19% were classified as ‘oncogenic’ and 5% were identified as potentially targetable. Conclusions: We here developed an NGS-based technology for ctDNA profiling in heavily pretreated patients receiving MTB-recommended therapies. Non-invasive genotyping from plasma robustly identifies targetable aberrations and allows comprehensive tumor genotyping. Monitoring of ctDNA during treatment and at disease progression facilitates early prediction of treatment response and profiling of temporal clonal heterogeneity that could enable subsequent treatment selection.
Breast cancer–specific mortality in invasive lobular versus ductal carcinoma over 30 years.
636 Background: Invasive lobular carcinoma (ILC) differs biologically from invasive ductal carcinoma (IDC) and has been associated with delayed recurrence. However, long-term patterns of breast cancer-specific mortality (BCSM) following ILC remain incompletely described. We aimed to characterize temporal patterns of BCSM associated with ILC vs IDC over extended follow-up. Methods: We conducted a population-based study using the SEER program. Women diagnosed with stage I–III IDC or ILC from 1990 to 2012 were included. BCSM was the primary endpoint, with death from other causes treated as a competing event. Unadjusted cumulative incidence functions estimated BCSM by histology. Fine-Gray competing risks models were used to compare histologies overall and within hormone receptor (HR)-defined subgroups, with all models adjusted for age at diagnosis, year (y) of diagnosis, HR status (where applicable), tumor size, nodal status, tumor grade, surgery, radiation, and chemotherapy. Non-proportional effects were identified visually and modeled using time-varying coefficients. Landmark competing risks analyses assessed late BCSM among long-term survivors. Results: Among 423,479 women included, 41,027 (9.7%) had ILC and 382,452 (90.3%) had IDC; median follow-up was 16.7 y (range 0.1–33 y). During follow-up, 77,926 breast cancer deaths and 111,814 deaths from other causes occurred. In unadjusted analyses of the overall population, BCSM was lower for ILC than IDC at 5 and 10 years and higher for ILC at 20 and 30 years (Table). In adjusted Fine-Gray models, lobular histology demonstrated a significant time-varying association with BCSM (p<0.001). Associations between histology and BCSM differed by HR status (p for interaction=0.0029). In time-varying models restricted to HR+ disease, the adjusted subdistribution hazard ratio (sHR) for ILC versus IDC increased over time, reaching 1.19 (95% CI 1.15–1.23) at 10 y, 1.34 (1.28–1.41) at 20 y, and 1.44 (1.36–1.54) at 30 y. In landmark analyses among HR+ survivors, ILC remained associated with higher late BCSM beyond 10 y (sHR 1.36, 95% CI 1.29–1.43) and beyond 15 y (sHR 1.32, 95% CI 1.20–1.45). Conclusions: ILC is associated with a distinct temporal pattern of BCSM compared with IDC. Although unadjusted early BCSM is lower for ILC, adjusted risk increases over time and exceeds that of IDC in the late post-diagnosis period, particularly among HR+ disease. These findings highlight the importance of long-term risk assessment and survivorship strategies tailored to lobular histology. Unadjusted cumulative incidence of BCSM by histology (%; 95% CI). Overall population HR+ Y since diagnosis IDC ILC IDC ILC 5 9.8 (9.7–9.9) 7.3 (7.0–7.5) 6.5 (6.4–6.6) 6.4 (6.1–6.6) 10 15.0 (14.9–15.2) 14.3 (13.9–14.6) 11.9 (11.8–12.0) 13.4 (13.1–13.8) 20 19.6 (19.5–19.8) 21.6 (21.2–22.1) 17.2 (17.0–17.4) 21.0 (20.5–21.4) 30 22.0 (21.8–22.2) 24.5 (23.9–25.2) 19.8 (19.5–20.0) 23.9 (23.1–24.6)
Pathologic complete response in rare histologic subtypes of early-stage triple-negative breast cancer in the era of immunotherapy.
593 Background: The addition of immunotherapy (IO) to chemotherapy has improved outcomes in early-stage triple-negative breast cancer (eTNBC). Rare histologic subtypes, like lobular and metaplastic, are managed using the same treatment algorithms as ductal TNBC but historically have been associated with worse outcomes. Whether the benefits of IO extend to these rare subtypes in real-world practice remains unclear. Methods: We used the National Cancer Database to retrospectively identify patients diagnosed with stage II-III TNBC who received neoadjuvant therapy from 2021 to 2022, after FDA approval of IO for eTNBC. TNBC was categorized as ductal, lobular, metaplastic or other. Logistic regression was used to assess pathologic complete response (pCR) stratified by IO use. All models were controlled for key demographic and clinicopathologic factors. Results: We identified 17,006 patients with stage II–III TNBC (mean age 55.0 years). Most patients had ductal histology (91.1%), with smaller proportions of metaplastic (2.5%), and lobular (1.9%). Overall, 11,132 (65.5%) patients received IO and achieved a higher pCR rate than those who did not receive IO (45.2% vs 33.1%). pCR rate differed significantly by histologic subtype treated with neoadjuvant chemotherapy, both with and without IO. Among patients who received IO, pCR rate was highest in ductal TNBC (47%) and was significantly lower in lobular (18.9%) and metaplastic (17.6%) tumors (p<0.001). Similarly, in patients who did not receive IO, ductal TNBC had the highest pCR rate (34.6%) with metaplastic and lobular subtypes having lower pCR rates (12.5% and 14.3%, respectively; p<0.001). After covariate adjustment, all non-ductal subtypes had significantly lower odds of pCR compared to ductal TNBC regardless of receipt of IO. This was most notable for metaplastic TNBC with an odds ratio [OR] of 0.19 (95% CI 0.10–0.33) with IO and OR 0.13 (95% CI 0.04–0.44) without IO. Lobular TNBC was also associated with significantly lower odds of pCR in IO-treated patients (OR 0.50, 95% CI 0.28–0.90) with similar trends observed in patients treated without IO. Conclusions: In this national real-world cohort, we demonstrate that despite the adoption of neoadjuvant IO for eTNBC and improved pCR rates overall, rare histologic subtypes continue to experience inferior treatment outcomes. Metaplastic and lobular TNBC had persistently low pCR rates, regardless of IO use. These results highlight the urgent need for novel therapeutic strategies and dedicated clinical trials for these rare histologic subtypes.
Apalutamide in Chinese patients with metastatic hormone-sensitive prostate cancer (mHSPC): Final analysis from the retrospective real-world CAPABLE study.
e17103 Background: Apalutamide (APA) combined with androgen deprivation therapy (ADT) is the standard care for mHSPC and is associated with significant survival benefits. Given limited data from Chinese patients (pts), this study aimed to conduct the largest observational investigation to date to assess the real-world effectiveness and safety of APA plus ADT in Chinese pts with mHSPC, with a focus on prostate-specific antigen (PSA) decline and disease progression. Methods: This retrospective, multicenter observational study enrolled adult pts with mHSPC who initiated on APA plus ADT between 1 Jan 2022 and 31 May 2024 (index date), with follow-up through 31 May 2025, utilizing data from chart review. The observation period for each pt spanned from the index date to loss to follow-up, death, or 1-year follow-up. The primary endpoint was the proportion of pts achieving PSA≤0.2 ng/mL (PSA0.2) at Month (M) 3. Other endpoints included proportion of pts achieving a decrease in PSA ≥50% or ≥90% (PSA50/90), PSA progression, clinical and radiographic disease progression events within 12 mo. The number and proportion of pts achieving PSA0.2 or PSA50/90 along with their 95% confidence intervals (CIs) were determined by using Clopper–Pears on exact method on the basis of observed case data. Subgroup analyses were performed by age ( < 65, ≥65 to < 75, and ≥75 yr) and Gleason score (≤7 or > 7) on PSA0.2. Adverse drug reactions (ADRs) were collected for safety evaluation. Results: There were 300 pts with mHSPC treated with APA plus ADT analyzed. Median treatment duration was 12.8 (range 0.1–13.5) mo. Baseline characteristics were as follows: median age 72 (range 40–97) yr, Gleason score > 7 in 84% (172/204) of pts, tumor stage T3 in 22/84 and T4 in 51/84 pts, median PSA100 (range 0.1–5000) ng/mL. PSA0.2 response was 41.1% at M3, increasing to 62% at M6 and 69.7% at M12. PSA50 and PSA90 responses were 98.8% and 92% at M3, respectively. PSA progression (increase ≥50% and ≥5 ng/mL above nadir) occurred in 7 pts; clinical and radiographic disease progression occurred in 2 pts and 1 pt. Regarding safety analysis, ADRs were reported in 13% of pts, with ADRs (grade 3–4) reported in 1%. 4 deaths were reported. PSA0.2 response did not show meaningful difference across subgroups. Conclusions: The CAPABLE, the largest published APA real-world study in China, reveals a notably high PSA response for APA plus ADT, with infrequent progression reported, indicating a favorable prognosis for pts with mHSPC. The regimen also has a tolerable safety profile. PSA response among pts with mHSPC after APA plus ADT treatment. % (n/N) 95% CI PSA0.2M3M6M12 41.1% (76/185)62% (98/158)69.7% (99/142) 33.9%–48.5%54%–69.6%61.5%–77.1% PSA50M3M6M12 98.8% (160/162)97.1% (134/138)95.3% (121/127) 95.6%–99.9%92.7%–99.2%90%–98.2% PSA90M3M6M12 92% (149/162)91.3% (126/138)92.9% (118/127) 86.7%–95.7%85.3%–95.4%87%–96.7%
Equity in breast cancer research authorship: Country, gender, and income representation in phase III trials presented at the ASCO Annual Meeting (2015–2025).
11083 Background: Equitable representation in global oncology research is essential for scientific validity, generalizability, and ethical trial conduct. However, leadership in clinical research remains concentrated in high-income countries (HICs), with persistent gender inequities. We evaluated longitudinal trends in geographic, economic, and gender representation among authors of Phase III breast cancer trials presented at the ASCO Annual Meeting. Methods: We conducted a retrospective analysis of abstracts accepted to the ASCO Annual Meeting from 2015–2025 within breast cancer tracks, including metastatic and local/regional/adjuvant categories. Abstracts were identified using keyword searches for “phase” and included if they reported Phase III clinical trial data. For each eligible abstract, data were extracted for first and senior (last) authors, including institutional affiliation, country, World Bank region, and World Bank income classification. Author gender was assigned using a hierarchical approach incorporating culturally associated names, publicly available professional profiles, and genderize.io. Differences in authorship distribution by country were assessed using a univariate generalized linear model with country as a fixed effect. Results: Of 1,199 screened abstracts, 420 met inclusion criteria. Authorship was dominated by North America (44%) and Europe/Central Asia (40%), with representation from Latin America/Caribbean and Middle East/North Africa/Afghanistan/Pakistan each < 1%. The United States accounted for 40.7% of all authorship. East Asia representation increased from 2.8% (2015) to 19.1% (2025), driven by China, South Korea, and Japan. Country effect on authorship share was significant (F = 3.381, p = 0.001), while year was not (F = 0.000, p = 1.000), indicating persistent structural hierarchies. Overall, 93% of authors were affiliated with HICs, ~7% with upper-middle–income countries, and < 1% with lower-middle–income countries; no senior authors were from lower-middle–income countries. Gender distribution was 61.7% male and 37.7% female. Only Germany demonstrated female predominance in senior authorship among top contributing countries, while Japan exhibited 100% male senior authorship. Conclusions: Phase III breast cancer research presented at ASCO remains structurally concentrated in high-income countries with persistent geographic, economic, and gender inequities. Low- and middle-income countries remain largely excluded from academic leadership, and senior authorship remains male-dominated. These findings demonstrate enduring structural imbalances in global oncology research production and leadership, underscoring the need for equity-focused funding models, inclusive trial governance, and capacity-building research partnerships.
Impact of immunotherapy infusion timing on overall and progression-free survival in advanced NSCLC.
e20573 Background: Circadian rhythms regulate immune function through central and peripheral molecular clocks, modulating T-cell activity, antigen presentation, and cytokine release in a time-dependent manner. Preclinical models and retrospective studies suggest that morning hours may represent a period of enhanced antitumor immune responsiveness. However, despite several retrospective analyses evaluating the impact of immunotherapy infusion timing, further investigation is needed to clarify its clinical relevance specifically in lung cancer, particularly in patients with stage IV NSCLC. Therefore, the aim of the present study is to evaluate the association between immunotherapy infusion timing and clinical outcomes, including overall survival and progression-free survival. Methods: We conducted a retrospective cohort study including patients with stage IV NSCLC treated with immune checkpoint inhibitors (ICIs) between 2016 and 2025 in the Instituto Oncologico de Cordoba (IONC). Patients were classified according to infusion timing: before 12:00 (AM group) or after 12:00 (PM group). Clinical characteristics, tumor PD-L1 status, and concomitant treatments were collected. Kaplan–Meier estimates were used for survival analysis. Multivariate Cox regression models adjusted for relevant clinical and biological covariates were performed. Results: Fifty-nine patients were included (AM: n=24; PM: n=35). ORR was higher in the AM group (50% vs. 37.1%), as was the proportion of long-term survivors (87.5% vs. 45.7%). Median PFS was 9.5 months in the AM group vs. 4.3 months in the PM group (p=0.01). Median OS was 21.3 vs. 11.8 months, respectively (p=0.01). After adjustment, morning infusion remained independently associated with lower risk of progression (HR 0.38; 95%CI 0.19–0.79; p=0.01) and death (HR 0.48; 95%CI 0.24–0.98; p=0.04). Conclusions: Our findings suggest that the timing of immunotherapy administration may impact clinical outcomes in patients with advanced NSCLC. Morning administration was associated with improved survival and treatment response. As this is a low-cost, modifiable variable, it deserves further investigation in prospective clinical trials aimed at optimizing treatment efficacy through chronomodulated immuno-oncology strategies.
IMforte: Quality-adjusted time without symptoms or toxicity (Q-TWiST) analysis of first-line maintenance (1Lm) treatment (Tx) with lurbinectedin (lurbi) + atezolizumab (atezo) vs atezo in extensive-stage small cell lung cancer (ES-SCLC).
8086 Background: IMforte (NCT05091567) is the first positive phase 3 study of 1Lm in ES-SCLC to demonstrate statistically significant and clinically meaningful progression-free survival (PFS) and overall survival (OS) benefits (stratified hazard ratios, 0.54 and 0.73) with lurbi + atezo vs atezo. The combination was generally well tolerated based on safety findings and patient-reported outcomes. These data led to the approval of lurbi + atezo as 1Lm Tx for adults with ES-SCLC in the US and Switzerland in 2025. Here, we describe a post hoc Q-TWiST analysis using IMforte data to further elucidate the benefit-risk profile of lurbi + atezo. Methods: Eligible pts with ES-SCLC who were progression free after induction with atezo, carboplatin, and etoposide were randomized 1:1 to receive lurbi + atezo or atezo alone every 3 weeks. Survival time was partitioned into 3 health states: toxicity (TOX; time with grade ≥3 adverse events before disease progression), TWiST (time without TOX before disease progression), and relapse (REL; time from disease progression to death). The mean time spent in each health state was estimated using restricted mean survival times, calculated as area under the Kaplan-Meier curve. Q-TWiST was the sum of the mean time in each health state adjusted by respective utility weights, derived from EQ-5D-5L data. Results: Analyses were performed on all randomized pts from IMforte (lurbi + atezo, n = 242; atezo, n = 241) as of July 29, 2024, with a median follow-up of 15 months (mo). Utility weights in lurbi + atezo and atezo arms were 0.84 and 0.83 in TWiST, 0.83 and 0.83 in TOX, and 0.78 and 0.76 in REL health states. Pts in the lurbi + atezo arm spent most of their survival time in the TWiST state (66% vs 50% for atezo), and their mean duration of TWiST was substantially longer vs the atezo arm (9.8 vs 6.4 mo; Table). Lurbi + atezo arm pts spent more time in the TOX state vs atezo (0.7 vs 0.3 mo) but less time in the REL state (4.4 vs 6.1 mo). The lurbi + atezo arm had longer mean Q-TWiST vs atezo (12.2 vs 10.2 mo), representing a clinically important 14.9% gain in utility at the maximum follow-up of 26 mo. Conclusions: Lurbi + atezo pts had more time without toxicity before disease progression vs atezo and showed a clinically important improvement in quality-adjusted survival, further supporting a favorable benefit-risk profile of lurbi + atezo as 1Lm Tx for ES-SCLC. Clinical trial information: NCT05091567 . Mean duration of each health state, Q-TWiST, PFS, and OS. Mo, Mean (95% CI) Lurbi + Atezon = 242 Atezon = 241 Difference Relative Gain Q-TWiST 12.2 (11.1, 13.2) 10.2 (9.2, 11.3) 1.9 (0.5, 3.4) 14.9% TWiST 9.8 (8.4, 11.2) 6.4 (5.2, 7.7) 3.4 (1.5, 5.2) TOX 0.7 (0.5, 0.9) 0.3 (0.1, 0.5) 0.4 (0.1, 0.6) REL 4.4 (2.8, 6.0) 6.1 (4.6, 7.6) −1.8 (−4.0, 0.4) PFS 10.5 (9.1, 11.9) 6.8 (5.4, 8.1) 3.7 (1.8, 5.6) OS 14.8 (13.5, 16.1) 12.9 (11.6, 14.2) 2.0 (0.1, 3.8)
Incidence and risk: The epidemiology and long-term outcomes of early-onset luminal B breast cancer.
e12753 Background: Early-onset breast cancer is an increasing public health concern, with younger women disproportionately affected by aggressive subtypes such as Luminal B disease. Despite advances in systemic therapy, population-level data on long-term outcomes in this subgroup remain limited. We conducted a population-based study using the SEER Incidence 17 Registries database (November 2024 submission; 2000–2022) accessed via SEER*Stat v9.0.42.2. Female patients with invasive Luminal B breast cancer were identified using the SEER molecular subtype variable and stratified by age at diagnosis (18–39). Age-adjusted incidence rates were calculated and trended over time using Joinpoint v5.4.0. Five- and ten-year breast cancer–specific survival were estimated using SEER survival sessions to evaluate temporal patterns in short- and long-term outcomes. Methods: Using SEER Incidence 17 Registries (2000–2022), we evaluated incidence and 5- and 10-yearcause-specific survival among women aged 15–39 diagnosed with Luminal B breast cancer.Analyses were conducted using SEER*Stat v9.0.42.2, with temporal trends assessed viaJoinpoint v5.4.0. Results: Using SEER 17 registries (2010–2022), incidence of Luminal B breast cancer among women aged 15–39 increased across all age strata. The highest absolute incidence was observed in women aged 35–39, with a significant rise through 2014 followed by plateauing thereafter, while younger cohorts (20–34) demonstrated steady, incremental increases over the study period. Survival analyses revealed divergent temporal patterns. Five-year breast cancer–specific survival modestly improved across age groups diagnosed between 2010 and 2017, most notably among women aged 25–29 and 30–34, consistent with advances in systemic therapy and endocrine optimization. In contrast, ten-year cause-specific survival declined among women aged 30–34 and 35–39 diagnosed between 2010 and 2012, despite stable or improving short-term outcomes. This discordance suggests that early survival gains have not translated into durable long-term benefit, highlighting persistent late recurrence risk in young patients with Luminal B disease. Collectively, these findings demonstrate a growing incidence of early-onset Luminal B breast cancer accompanied by short-term survival improvements but worsening long-term outcomes in key age subgroups. Conclusions: Once thought uncommon, early-onset Luminal B breast cancer is increasing in incidence, with modest improvements in short-term survival but persistent declines in long-term outcomes. These population-level findings suggest that contemporary therapies improve early disease control without ensuring durability, underscoring the need for policies and research strategies focused on long-term risk reduction and survivorship in young women.
Analyzing variants and methylation in complex genomic regions using targeted long-read nanopore sequencing: A PKD case study.
e22644 Background: In oncology, actionable genomic and epigenomic alterations often occur in repetitive or other structurally complex regions. However, many targeted methods rely on short reads or PCR amplification, limiting resolution. Methods that preserve long-read context and native epigenetic information are therefore needed to interrogate this complexity without sacrificing scalability or cost efficiency. Here, we describe an Agilent-enabled targeted nanopore sequencing workflow for simultaneous native variant and methylation analysis, using autosomal dominant polycystic kidney disease (ADPKD) as a case study for resolving methylation and challenging genomic architecture. Methods: Assay performance was evaluated using SureSelect-based probe sets targeting multiple genomic regions across Genome in a Bottle (GIAB) reference samples. Libraries were sequenced on Oxford Nanopore platforms and analyzed using an integrated workflow including alignment, variant calling, and methylation profiling. Clinical applicability was assessed using a targeted ADPKD panel evaluated in a clinically verified patient sample and HG002 GIAB controls. Results: Across 634 filtered target regions, single-nucleotide variant detection achieved a mean precision of 98.5% and recall of 99.5%, and average methylation calling precision of 91% relative to GIAB truth sets, with consistent enrichment and coverage. With 1µg gDNA input per sample and 8-plex, mean on-target coverage exceeded 120x across genes, with fold enrichment greater than 1,600x. Long reads accurately resolved PKD1 despite highly homologous pseudogenes. Target variant calls were completely concordant with known patient variants and GIAB references. Conclusions: Together, these results indicate that Agilent-enabled targeted nanopore sequencing resolves variants in complex genomic regions, including loci with high homology or limited PCR accessibility, while preserving native methylation. Ongoing work focuses on expanding target designs, incorporating additional genomic features, and evaluating performance in clinical oncology samples to develop panels that capture SNPs, STRs, and other oncology-related variants.
Prognostic impact of tumor suppressor and DNA damage repair gene mutations in oral cavity squamous cell carcinoma: A clinico-genomic analysis from a real-world database.
6065 Background: Oral cavity squamous cell carcinoma (OCSCC) has unique genomic features, yet molecular biomarkers predicting prognosis remain poorly defined. Prior surgical series and TCGA analyses demonstrated TP53 and TERT promoter mutations associate with worse outcomes, while DDR pathways may influence immunotherapy response. However, no study has systematically evaluated these mutations with linked treatment and survival data. This is the first real-world clinico-genomic analysis addressing this gap in OCSCC. Methods: Using a pre-specified protocol with IRB approval, we analyzed 381 OCSCC patients from the Flatiron Health-Foundation Medicine Clinico-Genomic Database. Inclusion required confirmed OCSCC, genomic profiling (~300 genes), and survival data. We evaluated tumor suppressors (TP53, CDKN2A), TERT promoter, PIK3CA, and DDR genes (BRCA1/BRCA2/PRKDC). IPTW adjusted for age, sex, stage, smoking, advanced disease, and TMB. A 90-day landmark eliminated immortal time bias. Complete case analysis handled missing data. IO cohort (n=213, 56%) received checkpoint inhibitors. Primary endpoint: OS from diagnosis; secondary: OS from IO initiation. Results: Stage IV was the strongest clinical prognostic factor (HR 1.64, 95%CI 1.29-2.08, p<0.0001). In IO-treated patients, TMB-high showed improved survival (HR 0.54, p=0.035). DDR pathway mutations were associated with markedly inferior outcomes from IO initiation (HR 2.34, 95%CI 1.00-5.49, p=0.049; median OS 5.7 vs 13.8 months; 12-month OS 17.4% vs 50.4%). TP53+CDKN2A co-mutation showed a trend toward worse survival versus TP53 alone (HR 1.50, 95%CI 0.99-2.27, p=0.056; median OS 9.8 vs 12.8 months; 12-month OS 34.7% vs 51.5%). Conclusions: In this first real-world clinico-genomic analysis of OCSCC, TP53 mutation was associated with worse OS, and TP53+CDKN2A co-mutation identified an even higher-risk subset with nearly halved median survival (20.9 vs 44.5 months) compared to wild-type. CDKN2A co-occurred with TP53 in 95% of cases. TERT promoter mutations confirmed their adverse prognostic role. Notably, PIK3CA mutation showed favorable prognosis (HR 0.59), potentially relevant for targeted therapeutics. DDR pathway mutations predicted particularly poor outcomes following immunotherapy. These findings provide a molecular framework for risk stratification in OCSCC and warrant prospective validation. Prognostic impact of gene mutations on overall survival in oral cavity cancer. Genes HR (95%CI) p-value Median OS (MT vs WT) 12-mo OS (from diagnosis) TP53+CDKN2A co-mutation 1.83 (1.23-2.72) 0.003 20.9 vs 44.5 mo 76.5% vs 83.9% TP53 1.72 (1.20-2.47) 0.003 26.0 vs 44.5 mo 80.6% vs 85.1% CDKN2A 1.34 (1.04-1.73) 0.024 20.9 vs 34.2 mo 77.3% vs 83.6% TERT promoter 1.35 (1.01-1.80) 0.041 24.4 vs 38.0 mo 77.6% vs 88.8% PIK3CA 0.59 (0.42-0.85) 0.004 51.3 vs 25.7 mo 83.5% vs 81.0%
Impact of <i>KRAS</i> sub-mutations in metastatic colorectal cancer patients (mCRC).
e15535 Background: KRAS mutations are established predictive and prognostic biomarkers in metastatic colorectal cancer (mCRC). However, the clinical relevance of specific KRAS sub-mutations and their interaction with chemotherapy regimens remains incompletely defined. We evaluated the impact of distinct KRAS sub-mutations on overall survival (OS) and progression-free survival (PFS) in a consecutive cohort of patients with mCRC. Methods: We retrospectively analyzed 126 consecutive patients with mCRC treated at a single institution. Tumor molecular profiling was performed using Next Generation Sequencing (NGS) and Polymerase Chain Reaction (PCR) to identify KRAS and NRAS mutations. Survival outcomes were analyzed according to KRAS sub-mutation status and first-line chemotherapy regimen (oxaliplatin- vs irinotecan-based). OS and PFS were estimated using the Kaplan–Meier method and compared with the log-rank test. Hazard ratios (HRs) were calculated using Cox proportional hazards models. All tests were two-sided. Results: Forty-nine patients (39%) harbored KRAS mutations. Median age was 68 years. Liver was the most common metastatic site (51%); 29% of patients had ≥2 metastatic sites. First-line treatment consisted of oxaliplatin-based regimens in 69% and irinotecan-based regimens in 16% of patients.Codon 12 KRAS mutations were associated with inferior OS compared with other variants. Median PFS for codon 12 mutations was longer with irinotecan-based therapy than with oxaliplatin-based therapy (22.5 vs 8 months, p sign < 0.05). Codon 13 mutations demonstrated similar median PFS (12 months) regardless of chemotherapy regimen or specific variant (G13D vs G13V). Non-canonical KRAS sub-mutations (codons 61 and 146) were associated with improved outcomes with oxaliplatin-based therapy (median PFS 17 vs 13 months, p sign < 0.05). Median OS was longest in non-canonical sub-mutations (23 months), followed by codon 13 (18 months) and codon 12 mutations (15 months). Concomitant genomic alterations were detected in 38% of cases, most frequently involving PIK3CA (10%) and TP53 (8%). Conclusions: KRAS mutations in mCRC are clinically heterogeneous. Codon 12 mutations confer poorer survival, whereas codon 13 and non-canonical mutations exhibit distinct prognostic and predictive profiles on the basis that codon 13 mutations do not completely abolish RAS GTPase activity, in contrast to codon 12 mutations, which result in a more profound functional impairment.Comprehensive molecular characterization may refine prognostic stratification and support personalized first-line treatment selection in mCRC.
Real-world effectiveness of first-line niraparib maintenance therapy in Korean patients with advanced ovarian cancer: A multicenter retrospective cohort study.
e17562 Background: Although first-line maintenance therapy with poly(ADP-ribose) polymerase (PARP) inhibitors has significantly improved progression-free survival in advanced epithelial ovarian cancer, the overall survival benefit of niraparib remains uncertain in randomized trials, largely due to substantial post-progression crossover to PARP inhibitors. Real-world data from clinical settings with limited crossover may therefore provide a more appropriate assessment of the survival impact of niraparib, particularly in underrepresented Asian populations. Methods: This multicenter, retrospective cohort study included patients with newly diagnosed FIGO stage III–IV EOC who completed first-line platinum-based chemotherapy between December 2019 and October 2022 at nine tertiary institutions in South Korea. Patients were categorized into those receiving niraparib maintenance and those with no maintenance. Propensity score matching (PSM) adjusted for baseline differences including age, neoadjuvant chemotherapy, and BRCA mutation status. Primary endpoints were progression-free survival (PFS) and overall survival (OS), analyzed using Kaplan–Meier and Cox models with predefined subgroup analyses. Results: A total of 554 patients were included (niraparib, n=248; no maintenance, n=306). In the unmatched cohort, niraparib was associated with significantly longer PFS (p=0.00017) and OS (p=0.0011). After 1:1 PSM, 189 matched pairs were analyzed. The 3-year PFS rate was higher with niraparib (43.1% vs. 25.7%; p=0.00011), as was the 3-year OS rate (86.3% vs. 74.7%; p=0.0046). Subgroup analyses showed PFS benefit in both BRCA-mutated (60.3% vs. 37.1%; p=0.0071) and BRCA wild-type patients (35.4% vs. 23.0%; p=0.017). OS benefit was evident in BRCA wild-type (p=0.017) but not BRCA-mutated patients (p=0.47). Crossover to subsequent PARP inhibitors occurred only in the no-maintenance group, more frequently in BRCA-mutated tumors (21.4%) than wild-type (4.1%). Niraparib benefit was most pronounced in patients undergoing primary debulking surgery with complete cytoreduction. Conclusions: First-line niraparib maintenance improved PFS regardless of BRCA status. OS benefit was observed in the matched cohort, particularly among BRCA wild-type patients with minimal crossover to post-progression PARPi.
Recurrence of ductal carcinoma in situ: A large South American multicenter analysis.
e12612 Background: Although ductal carcinoma in situ (DCIS) has minimal mortality, recurrence rates after surgery are clinically relevant, and approximately half of recurrences are invasive, leading to a reduction in both overall and disease-specific survival. Numerous risk factors for recurrence have been identified; however, for certain features such as DCIS size and margin status, the association remains less clear. The objective was to analyze the association between clinical, pathological, and therapeutic characteristics and the risk of recurrence of primary pure DCIS. Methods: A retrospective evaluation was conducted in a large cohort of 1,270 patients from 24 centres from South American. Recurrence-free survival (RFS) was estimated using the Kaplan–Meier method, and comparisons between groups were performed using the Wilcoxon test. Univariate and multivariate Cox proportional hazards models were fitted to assess the association between the variables of interest and the risk of recurrence over time. A significance level of 0.05 was applied for all analyses. Results: Higher recurrence-free survival was observed in cases treated with breast-conserving surgery, radiotherapy, adjuvant endocrine therapy, smaller tumor size, and nuclear grade 1 or 2. No significant differences in recurrence-free survival were found according to margin status. For each 5-mm increase in tumor size, the risk of recurrence increased by 6% (HR 1.06; 95% CI 1.01–1.13; p = 0.0378). Participants who did not receive endocrine therapy had a 119% higher risk of recurrence compared with those who did (HR 2.19; 95% CI 1.24–3.86; p = 0.006). Low-grade DCIS (nuclear grade 1 and 2) showed a 53% lower risk of recurrence than high-grade DCIS (HR 0.47; 95% CI 0.28–0.78; p = 0.0033). After adjustment in the multivariate model, only nuclear grade remained a significant independent predictor, with low-grade DCIS exhibiting a 45% lower risk of recurrence compared with grade 3 disease (HR 0.55; 95% CI 0.32–0.94; p = 0.03). Conclusions: These findings confirm the inherent complexity of identifying factors associated with recurrence risk in DCIS. While tumor size, absence of endocrine therapy, and high nuclear grade were significantly associated with higher risk of recurrence in the univariate analyses, only nuclear grade retained an independent and significant association in the multivariate analysis. This underscores the central prognostic role of nuclear grade and highlights the limitations of interpreting other clinical and therapeutic factors in isolation. Given the overall low recurrence rate of DCIS, larger studies with long-term follow-up are needed to refine risk stratification, optimize therapeutic decision-making, and advance toward more personalized management strategies, avoiding both undertreatment and overtreatment.
Real-world outcomes associated with tarlatamab for extensive-stage small cell lung cancer (ES-SCLC) in the Veterans Health Administration (VA).
e20153 Background: ES-SCLC remains an aggressive malignancy with a very poor prognosis. Tarlatamab, a DLL3-targeted bispecific T-cell engager, improves survival in previously treated ES-SCLC. However, real world outcomes of tarlatamab use outside of large medical centers, and specifically in the VA, have not been reported. Examination of toxicity and efficacy outcomes in the VA allows examination of a national cohort characterized by an older age and higher comorbidities. Methods: We conducted a retrospective cohort analysis of patients treated with tarlatamab from 6/6/2024 to 1/13/2026 using the VA Corporate Data Warehouse. Annual SCLC incidence was obtained from the VA Cancer Registry System. Clinical data was obtained by manual chart review. Descriptive statistics were used to summarize patient demographics, disease characteristics, treatment patterns, clinical outcomes, and safety outcomes. Results: An estimated 908 cases of ES-SCLC were estimated to have been diagnosed during the study interval. 52 patients received tarlatamab at 23 distinct hospital sites in 17 states (2 patients were treated at 2 sites). Patient characteristics: 90% male; median age 68 (range 43-81); 73% White, 8% Black and 8% Latino; ECOG 0 = 6 (12%), 1 = 27 (52%), 2 = 14 (27%), 3 = 2 (4%), unknown 3 (6%); 69% ES-SCLC at diagnosis. At the start of tarlatamab, 24 (46%) and 21 (40%) had liver and brain metastasis. The number of starts increased from 2.5/month to 4.1/month between the first and second half of the study interval, 20 (38.5%) were started as second line treatment. Outcomes: 43 patients were evaluable for response. Disease control rate was 46% (95% CI, 32.5%-61.1%). Median progression free survival was 2.6 months (95% CI 2.0-6.0) and median overall survival (OS) 4.9 months (95% CI: 3.4-NR) with 12 month- OS rate 27.6% (95% CI, 14.0%–54.3%). Safety: Any grade CRS occurred in 21 patients (40%) and recurred in 5 (10%); 91% and 9% of CRS episodes occurred in cycle 1 or 2 respectively. Grade 3+ CRS occurred in 3 (6%). Glucocorticoid and tocilizumab were used in 38% and 33% respectively. No recurrent CRS was grade 3-5. ICANS occurred in 13 (25%) patients, with no recurrence. No association was found between ICANS incidence and baseline brain metastasis. Grade 5 toxic events: CRS 1, ICANS 2, hepatotoxicity 1. Conclusions: An increasing but small fraction of ES-SCLC patients have received tarlatamab in the VA. Among the first 52 patients treated in VA, both outcomes and toxicity were numerically less favorable than reported in the DeLLphi-304 study with lower PFS and OS and higher risk of ICANS and G3 CRS with fatal toxicity in 4 (8%) patients. Analysis of patients with ES-SCLC treated outside of VA may further inform the efficacy and safety of tarlatamab in Veterans and guide future use in VA.
Effectiveness and safety of IBI310 combined with sintilimab versus sorafenib in the first-line treatment of advanced hepatocellular carcinoma (aHCC): A randomized, open-label, controlled, multicenter phase III clinical study.
4148 Background: Immune checkpoint inhibitors (ICIs) targeting PD-1/PD-L1 have demonstrated efficacy in aHCC. Despite improved outcomes with PD-1/PD-L1 inhibitor-based regimens, prognosis remains poor and there is a continued unmet need for alternative therapies with long-term survival benefits. This study aimed to evaluate the effectiveness and safety of IBI310 (anti-CTLA-4 antibody) combined with sintilimab (anti-PD-1 antibody) in the first-line treatment of aHCC. Methods: Pts were randomized in a 2:1 ratio to IBI310+sintilimab group or sorafenib group. The experimental group received IBI310 3mg/kg intravenously (IV) and sintilimab 200 mg IV on day 1 of every 3 weeks. The control group received sorafenib 400 mg orally twice daily (BID) continuously until disease progression, intolerable toxicity, death or other protocol-specified discontinuation criteria. During the study, the IBI310 dose was adjusted to 1 mg/kg every 6 weeks. Primary end points included overall survival (OS) and objective response rate (ORR)assessed by the independent radiology review committee (IRRC) per RECIST v1.1. Secondary endpoint included progression-free survival (PFS), disease control rate (DCR), safety, etc. Results: As of August 2022, 344 patients were enrolled and allocated to Group 1 (G1, IBI310 3mg/kg + sintilimab, n=84), Group 2 (G2, modified-dose IBI310 1mg/kg + sintilimab, n=145) and Group 3 (G3, sorafenib, n=115). Overall, PFS and ORR improved with IBI310+sintilimab vs Sorafenib. The median OS in the primary endpoint was 44.0 months(G1), 36.1 months(G2) and 22.9 months(G3), respectively. Confirmed ORRs were significantly higher in the combination therapy groups (G1: 41.7%; G2: 22.1%) versus the control group (2.6%). Median PFS of three groups were 13.5 months(G1), 6.1 months(G2) and 2.8 months(G3), respectively. Grade ≥3 treatment-related adverse events (TRAEs) occurred in 60.7% (G1), 34.7% (G2), and 35.1% (G3) of patients. Conclusions: Compared with sorafenib group, combination treatment of IBI310 + sintilimab as first-line treatment demonstrated survival benefits and a manageable safety profile in aHCC. Clinical trial information: NCT04720716 . Survival data. IBI310(3mg/kg)+Sintilimab(N=84) IBI310(1mg/kg)+Sintilimab(N=145) Sorafenib(N=115) mOS, m 44.0 36.1 22.9 Confirmed ORR, n(%) 35(41.7) 32(22.1) 3(2.6) mPFS, m 13.5 6.1 2.8
Real-world treatment patterns and adherence to adjuvant abemaciclib among patients with early hormone receptor–positive (HR+) breast cancer (BC).
530 Background: Adjuvant abemaciclib (2 years) is approved in combination with endocrine therapy (ET) for node-positive high-risk early HR+ BC. Although it improves invasive disease-free and overall survival, its long duration and toxicities increase treatment complexity. As adjuvant regimens become more intensive, long-term adherence is critical for real-world effectiveness. However, data outside clinical trials are limited. We examined treatment patterns and factors associated with adherence to abemaciclib in a younger population of patients with early BC. Methods: We conducted a retrospective cohort study using the Merative MarketScan Commercial Claims and Encounters database. Patients aged 18-64 years with early BC who received abemaciclib between 2017 and 2024 were identified. Index date was the date of the first abemaciclib claim. We included patients who underwent breast surgery within one year before the index date and had continuous enrollment for 6 months before and one year after index date. We excluded patients with metastatic disease prior to the index date. Medication adherence was assessed using the proportion of days covered (PDC), with adherence defined as PDC ≥80%. Multivariable logistic regression was used to examine factors associated with abemaciclib adherence at one and two years. Results: Among 640 patients (median age 51 years) treated with adjuvant abemaciclib (median follow up 1.5 years), 55% were adherent to therapy at one year. Adherence declined from 100% in month 1, to 66%, 57%, 55%, and 50% in months 2, 6, 12, and 24 (p<0.001). Overall, 84.5% of patients initiated abemaciclib at 150 mg, and 47.2% had no dose adjustments during treatment. On multivariable analysis of one-year adherence, patients prescribed lower abemaciclib doses (50 or 100mg) were less likely to be adherent compared to those prescribed 150 mg (aOR=0.52; 95%CI 0.31–0.90). Adherence to ET was also associated with higher abemaciclib adherence (aOR=3.63; 95%CI 2.55–5.18). Polypharmacy was associated with reduced abemaciclib adherence among patients taking two (aOR=0.56; 95%CI 0.37–0.85) or ≥3 drug classes (aOR=0.51; 95%CI 0.34–0.78) compared with 0–1 drug class. Patients with high-deductible health plans (HDHP) had higher odds of adherence compared to those with PPO insurance (aOR=2.10; 95%CI 1.23–3.59). At two years (n=213), younger age and adherence to ET were significantly associated with greater abemaciclib adherence. Conclusions: Abemaciclib adherence was low, 55% in year 1, and 50% in year 2. Although lower abemaciclib doses and polypharmacy were associated with lower odds of adherence, ET adherence was associated with higher odds. Adherence in HDHP patients may reflect demographics (White, young, higher income). These findings highlight the need for close patient monitoring and strategies to support long-term adherence to adjuvant treatment.