Real-world Patient Population Research Articles

External validation of Standardized KELIM and platinum-resistant recurrence scores in patients with advanced epithelial ovarian cancer

BackgroundNeoadjuvant chemotherapy followed by interval debulking surgery is currently a common treatment option for advanced epithelial ovarian cancer (EOC). The Standardized CA-125 ELIMination rate constant K (Std KELIM) and the Platinum Resistant Recurrence (PtRR) Score have been proposed as markers of tumor chemosensitivity. The aim of our study was to validate these tools for predicting platinum sensitivity in a real-world population of patients with advanced EOC treated with neoadjuvant chemotherapy.Experimental designAll patients with advanced EOC treated with neoadjuvant chemotherapy at the Institut Curie between 2000 and 2015 were included. The Std KELIM was calculated with the CA-125 concentrations during the first 100 days of chemotherapy. The predictive value of Std KELIM and PtRR scores for the risk of subsequent PtRR was assessed using receiver operating characteristic (ROC) curve analysis, logistic regression and calibration curve. Kaplan–Meier survival analysis was performed for the treatment-free interval from platinum (TFIp) therapy and overall survival (OS).ResultsStd KELIM data were available for 149 patients. The AUC was 0.67 for PtRR. A low Std KELIM was significantly associated with PtRR (OR = 0.19 (95% CI [0.06, 0.53], p = 0.002)) according to the univariate analysis. The calibration curve of the PtRR showed a slight but significant underestimation (p = 0.02) of the probability of platinum resistance. Favorable Std KELIM (≥ 1) alone and combined with the completeness of surgery were associated with significantly better survival in terms of TFIp and OS.ConclusionsStd KELIM is an early prognostic marker of chemosensitivity in a real-life setting complementary to surgical status. It could help the clinician in the early management of patients by identifying those with a worse prognosis.

Real-world clinical outcomes with fostamatinib for the treatment of refractory chronic immune thrombocytopenia: a single-center experience.

Fostamatinib is a spleen tyrosine kinase inhibitor indicated for the treatment of chronic immune thrombocytopenia (ITP) unresponsive to a previous treatment. Real-world studies evaluating the utilization and effectiveness of fostamatinib outside the context of a clinical trial are lacking. The objective of this analysis was to evaluate the effectiveness of fostamatinib for the treatment of ITP in a real-world cohort. We conducted a single-center, retrospective, observational study to evaluate the effectiveness of fostamatinib for the treatment of ITP. The primary endpoint was durable response as defined by the American Society of Hematology ITP response criteria. Secondary endpoints included overall response rate, time to response, and safety. Subgroup analysis was performed to assess frequency of durable response in key subgroups of patients based on prior therapies. Thirty-one patients treated with fostamatinib for ITP were included in our analysis. Patients had received a median of four prior lines of therapy. Ten patients (32%) achieved a durable response. Most durable responders maintained their response at 24 months (n = 7; 70%). The median time to response was 9 days. Four patients (13%) discontinued fostamatinib due to an adverse event. Subgroups who had higher rates of durable responses included those who had received two to three prior lines of therapy (40%), splenectomized patients (50%), and those who had not received prior rituximab (55%). Fostamatinib therapy in a real-world population of patients with heavily pretreated ITP led to a durable response in a third of patients, which was maintained for most responders.

The Multi-Institutional Medullary Thyroid Cancer Collaborative Registry: Can a Rare Tumor Registry Accurately Represent the Real-World Patient Population?

Background: Large population-based registries, such as the Surveillance, Epidemiology and End Results (SEER) Registry, help in the study of rare tumors, including medullary thyroid cancer (MTC), but lack data to understand the natural history of the disease. The Medullary Thyroid Cancer Collaborative Registry (MTCCoRe) is an exhaustive multi-institutional collection of demographic, clinical, and pathological data. To determine the extent to which MTCCoRe represents the real-world MTC population, we compared the characteristics of patients enrolled in MTCCoRe with patients enrolled in population-based cancer registries. Methods: Comparison of demographic and clinical characteristics of MTC patients who were enrolled in MTCCoRe, Texas Cancer Registry (TCR), California Cancer Registry (CCR), and SEER between 1995 and 2018. Results: A total of 1416 patients were identified in MTCCoRe, 329 in TCR, 2105 in CCR, and 3820 in SEER. Percentages of patients 20-54 years in MTCCoRe were 58.0%, 50.2% in TCR, 47.2% in CCR, and 44.8% in SEER (p < 0.0001). About half of the patients were female (55.9% in MTCCoRe, 61.4% in TCR, 59% in CCR, and 57.5% in SEER (p = 0.3). Percentages of Hispanic and Black patients differed among cohorts (10.1% and 3.8% for MTCCoRe, 23.7% and 8.2% for TCR, 24.8% and 4.9% in CCR, and 15.9% and 8.2% for SEER, respectively; p < 0.001). MTCCoRe patients presented with more advanced T and N classifications than patients in the other registries (MTCCoRe, 28.6% T3-4 and 49.4% N1; TCR, 12.7% and 32.2%; CCR, 18.6% and 32.4%; and SEER, 24% and 37.8%; p < 0.0001). Prevalence of M1 disease was 10% in MTCCoRe, 11.9% in TCR, 14.1% in CCR, and 9.5% in SEER (p < 0.0001). In the MTCCoRe, 11.4% underwent systemic therapy (compared with 0.3% in TCR and 5.6% in CCR). Conclusions: The clinicodemographic profile of patients with MTC enrolled in a multi-institutional registry differs from those enrolled in population-based databases, with lower proportions of Hispanic and Black patients but additive data on treatment modalities. Moving forward, MTCCoRe and other registry and clinical trial enrollment efforts should intentionally include underrepresented groups via community engagement techniques, patient stakeholder involvement, and inclusion of languages other than English in study materials to yield more generalizable results and conclusions.

Rigid Sternal Fixation and Enhanced Recovery for Opioid-Free Analgesia After Cardiac Surgery

BackgroundWe evaluated the individual contributions of rigid-plate fixation (RPF) and an enhanced recovery protocol (ERP) on postoperative pain, opioid use, and other outcomes after median sternotomy as they were sequentially adopted into practice. MethodsThis single-center, retrospective, case-cohort study compared outcomes between median sternotomy patients (all comers) who underwent operation before implementation of RPF or ERP (“controls”), patients closed with RPF before ERP implementation (“RPF-only”), and patients managed with RPF and ERP during early “RPF+ERP-2020” and late “RPF+ERP-2022” implementation. ResultsThe analysis included 608 median sternotomy patients (mean age, 65.7 ± 10.8 years; 29.6% women). Of those, 59.2% were isolated coronary artery bypass grafting, 7.7% were isolated valve procedures, and the rest were mixed/concomitant procedures. Median in-hospital, postoperative opioid administration was 172.5 morphine milligram equivalents (MMEs) in the control cohort vs 0 MMEs for RPF+ERP-2022 (P < .0001), despite similar or slightly reduced patient-reported pain scores. The proportion of patients discharged directly to home was 66.2% for controls, 79.6% for RPF-only (P = .010), and 93.5% for RPF+ERP-2022 (P < .0001). Median opioids prescribed at discharge were 600 MMEs for controls and 0 for RPF+ERP-2020 and RPF+ERP-2022 (P < .0001). At discharge, 86.7% of RPF-only patients received prescription opioids vs 5% in RPF+ERP-2020 and 4.3% RPF+ERP-2022 (P < .0001). These outcomes occurred without increased readmissions. ConclusionsSystematic implementation of RPF and ERP was associated with a significant and clinically meaningful decrease in opioid use in this large, real-world patient population.

OPTImal PHARMacological therapy for patients with heart failure: Rationale and design of the OPTIPHARM-HF registry.

Patients with heart failure (HF) remain often undertreated for multiple reasons, including treatment inertia, contraindications, and intolerance. The OPTIimal PHARMacological therapy for patients with Heart Failure (OPTIPHARM-HF) registry is designed to evaluate the prevalence of evidence-based medical treatment prescription and titration, as well as the causes of its underuse, in a broad real-world population of consecutive patients with HF across the whole ejection fraction spectrum and among different clinical phenotypes. The OPTIPHARM-HF registry (NCT06192524) is a prospective, multicenter, observational, national study of adult patients with symptomatic HF, as defined by current international guidelines, regardless of ejection fraction. Both outpatients and inpatients with chronic and acute decompensated HF will be recruited. The study will enroll up to 2500 patients with chronic HF at approximately 35 Italian HF centres. Patients will be followed for a maximum duration of 24 months. The primary objective of the OPTIPHARM-HF registry is to assess prescription and adherence to evidence-based guideline-directed medical therapy (GDMT) in patients with HF. The primary outcome is to describe the prevalence of GDMT use according to target guideline recommendation. Secondary objectives include implementation of comorbidity treatment, evaluation of sequence of treatment introduction and up-titration, description of GDMT implementation in the specific HF population, main causes of GDMT underuse, and assessment of cumulative rate of cardiovascular events. The OPTIPHARM-HF registry will provide important implications for improving patient care and adoption of recommended medical therapy into clinical practice among HF patients.

Safety and Efficacy of Dapagliflozin in Patients with Heart Failure with Reduced Ejection Fraction: Multicentre Retrospective Study on Echocardiographic Parameters and Biomarkers of Heart Congestion.

Objectives: Dapagliflozin has shown efficacy in clinical trials in patients with heart failure and reduced ejection fraction (HFrEF). However, real-world data on its use and outcomes in routine clinical practice are limited. We aimed to evaluate the utilisation and safety profile of dapagliflozin in a real-world population of HFrEF patients within the Marche region. Methods: Nine cardiology departments within the Marche region retrospectively included HFrEF patients who were initiated on dapagliflozin therapy in an outpatient setting. Data on medical history, comorbidities, echocardiographic parameters, and laboratory tests were collected at baseline and after 6 months. Telephone follow-up interviews were conducted at 1 and 3 months to assess adverse events. We defined the composite endpoint score as meeting at least 50% of four objective measures of improvement among: weight loss, NYHA decrease, ≥50% Natriuretic peptides (NP) decrease, and guideline/directed medical therapy (GDMT) up titration. Results: We included 95 HFrEF patients aged 66 ± 12 years, 82% were men, 48% had ischemic heart disease, and 20% had diabetes. At six months, glomerular filtration rate declined (p = 0.03) and natriuretic peptides levels decreased, on average, by 23% (p < 0.001). Echocardiographic measurements revealed a decrease in pulmonary artery pressure (p < 0.001) and E/e' (p < 0.001). In terms of drug therapy, furosemide dosage decreased (p = 0.001), and the percentage of the target dose achieved for angiotensin receptor-neprilysin inhibitors increased (p = 0.003). By multivariable Cox regression, after adjustment for age, sex, the presence of diabetes/prediabetes, and HF duration, higher baseline Hb concentrations (HR 1.347, 95% CI 1.038-1.746, p = 0.025), and eGFR levels (HR 1.016, 95% CI 1.000-1.033, p = 0.46). Conclusions: In a real-life HFrEF population, dapagliflozin therapy is safe and well-tolerated, improves echocardiographic parameters and biomarkers of congestion, and can also facilitate the titration of drugs with a prognostic impact.

Increase in blood pressure in patients with metastatic kidney cancer treated with combination checkpoint inhibitor and vascular endothelial growth factor receptor tyrosine kinase inhibitor therapy.

e24128 Background: The combination therapy of an immune checkpoint inhibitor (ICI) with a vascular endothelial growth factor receptor tyrosine kinase inhibitor (VEGFR-TKI) is considered a first line treatment option for patients with metastatic clear cell renal cell carcinoma (ccRCC). TKI-induced hypertension is a well-known potential side effect with VEGFR-TKIs however little is known about the real-world increase in systolic blood pressure (SBP) and diastolic blood pressure (DBP) in patients with and without underlying hypertension treated with this combination therapy. Methods: A retrospective study was performed that included patients with metastatic ccRCC who were treated at the University of Florida Health Cancer Center between June 2019 and September 2022 who received treatment with the combination of an ICI and VEGFR-TKI. The data collected included history of hypertension, patients use of anti-hypertensive therapy at baseline, SBP and DBP prior to initiation of therapy and at approximately one month after initiation of treatment. Results: We identified a total of 29 patients who met the inclusion criteria for our study. The median age was 68 years old (IQR 61-72) while 25 patients (86%) were male and 4 (14%) were females. There were 27 patients (93%) who were treated with axitinib with pembrolizumab, while 1 (3%) was treated with cabozantinib with nivolumab, and 1 (3%) was treated with lenvatinib with pembrolizumab. Out of the 29 patients, 11 (38%) did not have hypertension prior to therapy while 18 (62%) did have baseline hypertension and were receiving at least one anti-hypertensive treatment. In those patients without baseline hypertension, the median baseline SBP was 113 and the median SBP after one month of treatment was 144 (p = 0.01). Conversely, those patients with baseline hypertension, the median baseline SBP was 122 and median SBP after one month of treatment was 148 (p = 0.003). In those without hypertension at baseline, the mean SBP increase after one month was 27.3% while in those with baseline hypertension the mean increase in SBP of 17.0%. Conclusions: Our study demonstrates that in a real-world population of patients with metastatic ccRCC there is a statistically significant elevation of both SBP and DBP when treated with the combination of an ICI and VEGFR-TKI and that in those patients without baseline hypertension and not on anti-hypertensive therapy at baseline, there is a more pronounced increase in blood pressure. This data should reinforce the need to have close monitoring of SBP and DBP during therapy, regardless of whether the patient has underlying hypertension or not, and may help guide anti-hypertensive therapy during kidney cancer treatment.

Assessment of carcinoembryonic antigen-related cell adhesion molecule 5 expression by immunohistochemistry in real-world clinical samples of non-small cell lung cancer.

e20013 Background: Carcinoembryonic antigen-related cell adhesion molecule 5 (CEACAM5) is an emerging target of antibody-drug conjugate therapy for non-small cell lung cancer (NSCLC). High expression of CEACAM5 has been reported in approximately 25% of patients with lung adenocarcinoma (Lefebvre AM, et al. Lung Cancer. 2023; 184:107356). However, CEACAM5 expression has not been systematically examined in a real-world patient population with NSCLC. In this study, we evaluated our experience in the assessment of CEACAM5 expression by immunohistochemistry (IHC) in routinely diagnosed clinical samples. Methods: We assessed the expression of CEACAM5 by IHC on clinical biopsy/resection samples of consecutively diagnosed NSCLC from September 2022 to June 2023 at our institution, using the anti-CEACAM5 clone 769 antibody assay protocol developed for tusamitamab ravtansine clinical trials. Only cases adequate for PD-L1 22C3 and Oncomine Comprehensive Assay v3 NGS assay were included. CEACAM5 expression was scored independently by three pathologists based on the method proposed by Lefebvre et al. Expression levels were categorized as high (≥ 50% tumor cells at ≥ 2+ intensity), moderate (1–49% tumor cells at ≥ 2+ intensity), and negative (0 or 1+ intensity). Interrater reliability was assessed by Kendall’s coefficient of concordance (KCC) and Fleiss’ Kappa. Discordant classification was reviewed with the final classification achieved by consensus. Association with PD-L1 TPS and NGS results was determined by Chi-squared test. Results: This study cohort consisted of 150 consecutively diagnosed NSCLC, including 133 adenocarcinomas and 17 squamous cell carcinomas. The samples were derived from both primary (n = 138) and metastatic sites (n = 12). Both membranous and cytoplasmic CEACAM5 expression was observed in neoplastic cells, but was consistently absent in nonneoplastic cells. The prevalence of consensus high CEACAM5 membranous expression was 21% (n = 32) overall, 20% in primary (n = 28) and 33% (n = 4) in metastatic sites. The level of interrater agreement across all categories was moderate (KCC = 0.77). Interrater agreement between high CEACAM5 expression versus moderate/negative categories combined was also moderate (Kappa = 0.60). Challenging features included the determination of staining intensity and mixed membranous and cytoplasmic staining pattern, and cases near the cut-offs of the defined categories. CEACAM5 expression was not associated with PD-L1 TPS (p = 0.42) or EGFR mutations (p = 0.44). Conclusions: Our data showed that approximately 20% of routinely diagnosed clinical NSCLC samples had high CEACAM5 expression by IHC. The interrater reliability on the determination of high CEACAM5 expression was moderate among the three pathologists. We highlighted the challenging aspects in the evaluation of this biomarker.

Prognostic analysis and outcomes of metastatic pancreatic cancer patients receiving nab-paclitaxel plus gemcitabine as second or later-line treatment.

Pancreatic cancer (PC) first-line therapy often consists of polychemotherapy regimens, but choosing a second-line therapy after disease progression, especially following first-line FOLFIRINOX, remains a clinical challenge. This study presents results from a large, multicenter, retrospective analysis of Italian patients with metastatic PC (mPC) treated with Nab-paclitaxel/Gemcitabine (AG) as second or later line of treatment. Main objective of the study is to identify prognostic factors that could inform treatment decisions. The study included 160 mPC patients treated with AG in 17 Italian institutions. AG was administered according to labelling dose, until disease progression, unacceptable toxicity or patient refusal. Variations in schedules, dose modifications, supportive measures, and response evaluation were determined by individual clinicians' practice. AG was well-tolerated and exhibited promising clinical activity. The overall response rate (ORR) and the disease control rate (DCR) were 22.5% and 45.6%, respectively. Median progression-free survival (PFS) and overall survival (OS) were 3.9 and 6.8 months, respectively. Among the patients who received AG as a second-line therapy (n = 111, 66.9%), median PFS and OS were 4.2 and 7.4 months, respectively. Notably, in the 76 patients (68%) receiving AG after first-line FOLFIRINOX, an ORR of 19.7% and a DCR of 46.0% were observed, resulting in a median PFS of 3.5 and median OS of 5.7 months. The study identified specific clinical or laboratory parameters (LDH, NLR, fasting serum glucose, liver metastases, ECOG PS, and first-line PFS) as independent prognostic factors at multivariate level. These factors were used to create a prognostic nomogram that divided patients into three risk classes, helping to predict second-line OS and PFS. This study represents the largest real-world population of mPC patients treated with AG as a second or later line of therapy. It supports the feasibility of this regimen following first-line FOLFIRINOX, particularly in patients with specific clinical and laboratory characteristics who derived prolonged benefit from first-line therapy.

Survival benefit of autologous transplant (ASCT) for mantle cell lymphoma (MCL) in the California Cancer Registry (CCR).

e19043 Background: Extended follow up of the prospective Nordic MCL2 cohort shows ASCT in CR1 confers a median OS (mOS) of 12.7 y (Eskelund, BJH 2016). Incorporation of BTK inhibitors in 1L MCL is challenging the role of ASCT in an ongoing prospective trial (TRIANGLE, ASH 2022). The present study aims to evaluate the role of ASCT and the impact of social determinants of health (SDH) in a diverse real-world population of MCL patients. Methods: Adult MCL patients diagnosed from January 1, 2000 to December 31, 2020 in the CCR were identified with ICD-O-3 code 9673. The study was approved by UCLA IRB. OS was estimated using KM statistics, calculated from diagnosis to death/last follow-up. Univariate Cox proportional hazards modeling for lymphoma-specific survival (LSS) was performed for variables of interest; those significant at p ≤ 0.10 were incorporated in a stepwise multivariable regression excluding patients with missing data. Socioeconomic status (SES) variables were reported using census-block group data at diagnosis. Results: 5740 ethnically diverse patients were included (NH Whites, n=4038; NH Black, n=175; Hispanic, n=1057; Asian/Pacific Islanders, n=400). Median age at diagnosis was 69 y (IQR 61–68) and 71% were males. 4096 (71%) and 1346 (23%) patients received chemoimmunotherapy and were treated at an NCI/NCCN center, respectively. With a median follow-up of 33 m (IQR 9–76), mOS of the entire cohort was 4.4 y. ASCT patients (n=652, 11%) had improved mOS compared to non-ASCT (14.2 y vs 3.7 y, respectively p&lt;0.001), and 100-day TRM was 2.5%. In the univariable model for all subjects, age, Charlson Comorbidity Index (CCI), married, chemoimmunotherapy, ASCT, NCI/NCCN center, insurance, period of diagnosis, and community SES, poverty, and education were prognostic for LSS. Race, sex, and rural residence were not associated with LSS. Multivariable analysis of 4148 subjects showed significant predictors of LSS were age ≥ 70 y (HR 1.71, p&lt;0.001), ASCT (HR 0.54, p&lt;0.001), diagnosis after 2013 (HR 0.78, p&lt;0.001), CCI (Ref 0; 1-2 HR 1.22, p&lt;0.001; 3+ HR 1.94, p&lt;0.001), married (HR 0.86, p=0.003), NCI/NCCN treatment center (HR 0.77, p=0.001), higher education (top 40% with high school diploma vs. bottom 20%, HR 0.70, p&lt;0.001), higher overall SES (medium vs. low SES tertile, HR 0.81, p=0.003), and increased community poverty (middle 40% vs. bottom 20%, HR 1.14, p=0.043). Conclusions: Our data represent the largest real-world cohort describing the role of ASCT and SDH in MCL. A minority of patients received ASCT and had improved OS compared to non-ASCT patients. While follow-up of ongoing prospective studies will clarify the role of ASCT using contemporary 1L regimens, the present data suggest ASCT in select patients results in durable response with low TRM. Socially disadvantaged patients should be identified and offered supportive programs early in the disease course to mitigate inferior outcomes.

Sex influence on cancer immunotherapy efficacy and safety in advanced non-small cell lung cancer (NSCLC): A Canadian institution real-world experience.

e20618 Background: Males and females differ in innate and adaptive immune responses. This difference may also be reflected in their response to cancer immunotherapies. Immune checkpoint inhibitors (ICIs) have revolutionized the treatment for advanced NSCLC, however the impact of sex on treatment outcomes in these patients remains unclear. The aim of this retrospective cohort study was to evaluate sex-related differences in immunotherapy outcome in a real-world population of NSCLC patients treated with ICIs. Methods: Demographics, clinical, pathological and treatment characteristics were assessed. Treatment-related variables were analyzed to understand the differences in efficacy and safety outcomes including response rates, PFS, OS and all-cause treatment discontinuation (TD) in relation to sex. Results: 152 advanced NSCLC patients receiving first-line immunotherapy, either alone or in conjunction with chemotherapy, were included in the study cohort. Females were younger age, were more likely to be non-smokers, have non-squamous tumors and had a higher prevalence of pre-existing autoimmune diseases compared to males. Disease control (CR/PR/SD) was achieved in 65.8% of patients. Median PFS was 12.0 mo in females and 14.1 mo in males. Median OS for all patients was 15.8 mo; 16.1 and 15.7 mo in females and males respectively. No statistical differences based on gender were observed in PFS and OS (P = 0.767 and P = 0.657). In regression analysis older age and presence of liver metastases were independent poor prognostic factors. Gender was not an independent prognostic factor in PFS and OS. Notably, 44 or 28.9% patients developed symptomatic immune-related adverse events (ir-AEs) that led to TD (Table 1). ir-AE-related TD occurred at a significantly higher rate in females compared with males (Table 1; 38.2% vs 19.7%, RR = 1.90; 95% CI: 1.12 to 3.26; p = 0.018). GI toxicity, including hepatitis and colitis was predominantly observed in females, whereas pneumonitis was the most frequent ir-AE leading to TD in males. Conclusions: Despite no significant differences based on gender were observed in PFS and OS, our study showed that female patients with advanced NSCLC receiving ICIs are at a substantially greater risk of severe symptomatic ir-AEs and TD. This finding indicates that broad-based sex differences in this context could potentially exist and emphasizes the need for further investigations into the role played by gender in immunity and cancer immunotherapy treatment.[Table: see text]

Interaction between VEGF-A and immune checkpoint targets in triple-negative breast cancer and mechanisms of immune evasion and tumor progression.

1096 Background: Immune checkpoint inhibitors (ICIs) have revolutionized the treatment triple negative breast cancer (TNBC). However, not all patients with TNBC benefit from the addition of ICIs due to factors such as intrinsic and acquired resistance to ICIs, and complex interplay between tumor and immune cells in the tumor microenvironment (TME). Vascular endothelial growth factor (VEGF) promotes angiogenesis and potentially modulates tumor immune evasion. A phase I clinical trial has shown that a bispecific antibody to VEGF-A and PD-L1 produces encouraging tumor responses in advanced TNBC. In this study, we investigated the interaction between VEGF and various immune gene expression signatures including PD-L1 in a real-world breast cancer patient population. Methods: Comprehensive immune profiling, including the RNA-seq based gene expression assessment of 395 immune-associated genes, was performed on 120 formalin-fixed paraffin-embedded breast cancer samples. PD-L1 expression (Combined Positive Score, CPS ≥ 10%) was measured by immunohistochemistry (IHC; 22C3). Clinicopathologic variables were collected. Statistical associations between quantitative biomarkers, including 28 immune checkpoint genes, were calculated using Pearson correlations (r), and comparisons of quantitative biomarkers between groups were performed using the proportions test. For statistical significance, p&lt;0.05 was required. Results: The study cohort included 29 patients (24.2%) with TNBC and 91 (75.2%) with non-TNBC (including ER+/HER2- and HER2+). Most patients had metastatic tumors (n=92, 76.7%) and invasive ductal carcinoma (n=83, 69.2%). Among the TNBC group, 21 patients had PD-L1 positive tumors (72.4%), defined by CPS ≥ 10.In non-TNBC, VEGF has significant, though weak (r&lt;0.35) correlations with the expression of three checkpoint genes: AKT1 (r=0.35, p=0.00063), ICOS (r=0.34, p=0.00099), and TIM3 (r=0.29, p=0.0061). In TNBC, VEGF has significant, strong (r&gt;0.47) correlations with the expression of three other checkpoint genes: PD-1 (r=0.47, p=0.0094), PD-L1 (r=0.57, p=0.0012), and PIK3CA (r=0.6, p=0.00051) However, in TNBC, VEGF gene expression does not have a statistical association with PD-L1 IHC (CPS ≥/&lt; 10 (p=0.9)). Conclusions: Our findings suggest that there is an interplay between angiogenesis and an immunosuppressive tumor immune microenvironment in TNBC to a greater degree than in non-TNBCs. This supports the notion that angiogenesis mediators such as VEGF-A may enhance the expression of immunosuppressive checkpoint molecules, leading to immune evasion and tumor progression. Combination treatments of ICIs, especially anti-PD-1 therapy, with VEGF antibodies may be promising approaches to enhance the immune responses in TNBC, especially in tumors with CPS&lt;10, where the current frontline treatment is cytotoxic chemotherapy.

Efficacy of trifluridine/tipiracil in 3rd or 4th line of treatment in patients with advanced or metastatic colorectal cancer: A real-world data analysis with subgroups exploration.

e15576 Background: Patients with unresectable mCRC can achieve long-term overall survival (OS) thanks to modern systemic treatment and subsequent lines of therapy. With effective 1st, 2nd and next lines of therapy, their condition often allows further lines of treatment. Since publication of RECOURSE study, one of the most frequently used drugs in the 3rd or 4th line is trifluridine/tipiracyl (FTD/TPI). There is limited data on optimal selection of patients in order to obtain the greatest therapeutic gain with the least toxicity. The aim of this study was to find and define groups of patients who would benefit most from this treatment in a real-world mCRC patient population. Methods: Consecutive patients with unresectable or metastatic colorectal cancer (mCRC) started treatment with FTD/TPI between 1/Sep/2019 and 31/Dec/2023. Clinical factors including age, gender, primary location of colorectal cancer, BRAF, RAS and MSI-H status, ECOG performance status, baseline CEA level, location of metastases, response to treatment and AEs occurrence were analyzed. Survival analyses were performed using the Kaplan-Meier method, Log-rank and chi-square tests were used for comparison between groups. Data cut-off was 31/Jan/2024. Results: 822 medical records of patients with mCRC were analyzed. In total 261 patients treated with FTD/TPI were enrolled. 204 (78%) patients were treated with FTD/TPI in 3rd line (L3) and 57 (22%) in the 4th line (L4). Patients with RASmt were statistically more numerous in the L3 group; no other statistically significant differences in baseline characteristics was found between L3 and L4 groups. Estimated median OS (mOS) was 10.2 and 14.4 months in L3 and L4 group, respectively; no statistical significance was found between them (p = 0.0866; HR = 1.34, Cl 95% 0.9-1.9). Estimated median PFS (mPFS) was 7.4 and 4.6 months in L3 and L4 group, respectively, and statistically significant differences in mPFS was found in the L3 group in comparison to L4 (p = 0.0079; HR = 0.65, Cl 95% 0.5-0.9). Disease progression (PD) was found in 187 (92%) and 50 (88%) patients in the L3 and L4 group, respectively. PD was most common reason for discontinuing therapy. Most frequent serious AEs of grade 3 or higher were diarrhea, neutropenia and weakness. There were no grade 5 AEs and toxicity rarely led to discontinuation of FTD/TPI therapy. 102 (39%) patients were qualified for next line sequential systemic treatment after L3 or L4. Conclusions: Patients with mCRC who were treated with FTD/TPI in the 3rd line had better PFS than patients treated in 4th line, but mOS was statistically non-significantly better in L4 than L3, which requires further analysis. FTD/TPI is an effective therapy in subsequent lines of treatment for mCRC patients with acceptable toxicity.

The transformative role of digital health platforms: Bridging diversity gaps in cancer care in younger patient populations.

e13503 Background: Digital health platforms are transforming cancer care by offering unprecedented access to treatment options, including clinical trials (CTs). In this study, we analyzed data from the Leal digital health platform to identify demographic and behavioral trends among patients that may have implications for quality care and access to advanced treatments. Methods: Leal is an AI-based platform that matches cancer patients to CTs based on a self-reported medical profile. The profile includes parameters essential for CT matching, including disease status, stage, biomarker/mutational status, treatment history, comorbidities and demographics. The analysis incorporated data from 34,913 Leal Health community members, spanning a range of cancer types and encompassing all disease stages. Results: The digital platform attracted a significantly younger user base, while also reflecting key demographic trends consistent with the broader real-world cancer patient population. Specifically, 45% of the users were under 60 years old, and 20% were under 50, leading to a mean age of 60 years. This is notably younger than the general cancer patient population's mean age at diagnosis of 66 years (p = 0.03). The platform engaged diverse demographics, particularly among younger age groups (p&lt;0.0001). Notably, one-third of users under 40 and over a quarter under 60 belonged to minority groups. African American at younger ages represented about 10% of all signups, bridging a significant disparity for this minority group, even more so within the space of CT search and recruitment where African Americans represent up to 5% of patients. Moreover, younger users exhibited significantly higher disease knowledge (p&lt;0.0001), enhancing their potential for precise matching with advanced treatments. Conclusions: Digital health platforms uniquely attract younger and more diverse demographics, reflecting a broader spectrum of patient needs and experiences while significantly bridging racial disparity in CTs representation. This shift has profound implications for healthcare knowledge and outcomes. Our findings highlight the importance of adopting digital platforms to address the unique needs of the younger patient population.

Clinical impact of ICD implantation in octogenarians: a longitudinal cohort study

Abstract Background The implantation of defibrillators (ICDs) in patients over 80 years old is becoming increasingly common; however, evidence-based data regarding the actual clinical benefit in this population remain limited and contradictory. While age seems not to affect mortality and arrhythmia risk in octogenarians undergoing secondary prevention, the mortality reduction benefit given by ICD implantation for primary prevention appears to decrease with advancing age, likely due to the high number of non-arrhythmic deaths. Purpose This study aims to assess the long-term incidence of ventricular arrhythmias and mortality in a real-world cohort of octogenarian patients undergoing ICD implants. Methods This was an observational, retrospective, longitudinal cohort study. Demographic, clinical, and radiological data were collected for all patients undergoing ICD implantation between 2014 and 2021. Deaths from all causes and significant arrhythmic events (sustained ventricular tachycardias and ventricular fibrillation) detected during routine device controls and remote monitoring were recorded. Then was performed an univariate Kaplan-Meier analysis, stratifying the population by age in relation to the two study endpoints: ventricular arrhythmias and all-cause mortality. Results Out of a total of 700 patients, 512 underwent ICD implantation before the age of 80 (mean age at implantation 64±12), while 188 underwent ICD implantation after the age of 80 (mean age at implantation 82±3.2). No significant differences were found between these two groups in terms of gender (82% vs. 83% male; p 0.12), indication for implantation (74% vs. 75% primary prevention; p 0.79), and the presence of late gadolinium enhancement (LGE) on cardiac MRI (68% vs. 77%; p 0.14). Octogenarians were more frequently affected by ischemic heart disease (54% vs. 65%; p 0.01) and were more frequently treated with Amiodarone (17% vs. 24%; p 0.02). At the end of the average 8-year follow-up, octogenarians had significantly higher all-cause mortality than younger patients (HR=2.35 [1.88-3.16]; p&amp;lt;0.05), with survival curves diverging from 3 years after implantation. However, ventricular arrhythmic events were significantly reduced in octogenarian patients (HR=0.88 [0.87-0.89]; p&amp;lt;0.05). Conclusions In a real-world population of octogenarian patients, the clinical benefit of ICD implantation for primary prevention appears diminished, considering the trade-off between ventricular arrhythmias and mortality, in both ischemic and non-ischemic cardiomyopathy patients.

Polypharmacy and Bleeding Outcomes After Percutaneous Coronary Intervention.

Polypharmacy was reported to be associated with major bleeding in various populations. However, there are no data on polypharmacy and its association with bleeding in patients undergoing percutaneous coronary intervention (PCI).Methods and Results: Among 12,291 patients in the CREDO-Kyoto PCI Registry Cohort-3, we evaluated the number of medications at discharge and compared major bleeding, defined as Bleeding Academic Research Consortium Type 3 or 5 bleeding, across tertiles (T1-3) of the number of medications. The median number of medications was 6, and 88.0% of patients were on ≥5 medications. The cumulative 5-year incidence of major bleeding increased incrementally with increasing number of medications (T1 [≤5 medications] 12.5%, T2 [6-7] 16.5%, and T3 [≥8] 20.4%; log-rank P<0.001). After adjusting for confounders, the risks for major bleeding of T2 (hazard ratio [HR] 1.21; 95% confidence interval [CI] 1.08-1.36; P=0.001) and T3 (HR 1.27; 95% CI 1.12-1.45; P<0.001) relative to T1 remained significant. The adjusted risks of T2 and T3 relative to T1 were not significant for a composite of myocardial infarction or ischemic stroke (HR 0.95 [95% CI 0.83-1.09; P=0.47] and HR 1.06 [95% CI 0.91-1.23; P=0.48], respectively). In a real-world population of patients undergoing PCI, approximately 90% were on ≥5 medications. Increasing number of medications was associated with a higher adjusted risk for major bleeding, but not ischemic events.

Tafamidis medication adherence and persistence in patients with transthyretin amyloid cardiomyopathy in Japan.

This study aimed to describe baseline characteristics and adherence among patients with transthyretin amyloid cardiomyopathy (ATTR-CM) treated with tafamidis (VYNDAQEL®) in Japan using the Japanese Medical Data Vision (MDV) database. This study was a non-interventional, retrospective cohort study of adult (≥18years old) patients in the Japanese MDV claims database diagnosed with ATTR-CM and with at least two tafamidis prescriptions of dose strength 4×20mg/day between 1 March 2019 and 31 August 2021. The date of the first prescription was defined as the index date, with follow-up time defined as the time between the first and last prescription plus the days' supply from the last refill. Baseline characteristics were assessed during a 12month pre-index period. Adherence was measured using two metrics: (i) the modified medication possession ratio (mMPR), calculated by taking the sum of days supplied for all fills within the follow-up period, divided by the number of days of follow-up, and reported as a percentage, with patients classified as adherent with an mMPR of ≥80%, and (ii) the proportion of days covered (PDC), calculated by taking the total number of days' supply dispensed during the follow-up period divided by the number of days of follow-up, adjusting for any days' supply overlap. A total of 210 patients were identified; the mean (standard deviation) age of the cohort was 77 (5.9) years, and the majority (89%) were male. The most common baseline cardiovascular comorbidities were heart failure (85%), ischaemic heart disease (66%), hypertensive diseases (49%), and diabetes (35%); 75% of patients received heart failure medications in the 12months prior to index, with the most common being beta-blockers (49%), diuretics (48%), angiotensin receptor blockers (30%), angiotensin-converting enzyme inhibitors (22%), and sodium-glucose cotransporter-2 inhibitors (8.1%). Over an average 14month follow-up, mean mMPR was 96% with a median of 100% [inter-quartile range (IQR): 97-101%]; 93% of patients were adherent (defined as an mMPR≥80%). In the same follow-up period, mean PDC was 93.6% with a median of 99% (IQR: 93-100%). Persistence was high with 78% of patients having a 0day gap between prescription refills. This study found high adherence rates to tafamidis in this real-world Japanese patient population. Adherence rates in this study were similar to those reported by the tafamidis clinical trial and a previously published US commercial claims adherence analysis. Further studies should be conducted to assess the impact of real-world adherence on real-world outcomes.

Risk of Gastrointestinal Perforation in Patients With Rheumatic Diseases Exposed to Janus Kinase Inhibitors Versus Adalimumab: A Nationwide Cohort Study.

To compare the risk of gastrointestinal perforation (GIP), a rare but serious adverse event, in patients who a JAK inhibitor (JAKi; tofacitinib, baricitinib, upadacitinib, or filgotinib) versus adalimumab (tumor necrosis factor inhibitor) among a comprehensive real-world population of patients with rheumatic diseases. We conducted a nationwide population-based cohort study of the French national health data system, the exposed group that received a JAKi and the comparison group adalimumab. We included all individuals with a rheumatic disease who had their first dispensation of these treatments from July 2017 to December 2021. The primary endpoint was the occurrence of GIP (end of follow-up May 2022). Weighted hazard ratios (wHRs) were estimated with the inverse probability of treatment weighting method to account for confounding factors. Concomitant administration of systemic glucocorticoids, nonsteroidal anti-inflammatory drugs, and proton-pump inhibitors were time-varying variables. The cohort included 39,758 patients: 12,335 and 27,423 in the groups that received a JAKi and adalimumab (mean age 58.2 and 47.3 years; female 76% and 58%; rheumatoid arthritis 85.3% and 27.3%, and psoriatic arthritis/axial spondyloarthritis 14.7% and 72.7%), respectively. During follow-up, 38 and 42 GIPs occurred in the groups that received a JAKi and adalimumab groups; incidence rates were 2.1 (95% confidence interval [CI] 1.5-2.8) and 1.1 (95% CI 0.8-1.5) per 1,000 person-years, respectively. Rates of GIP did not differ between the groups that received a JAKi and adalimumab: wHR 1.1 (95% CI 0.7-1.9; P = 0.65). Despite the lack of power in some subgroup analyses, results were consistent whatever the subgroup of a type of JAKi received or subgroup with a type of rheumatic disease. In this nationwide cohort study, the rates of GIPs did not differ between groups of patients who received JAKi and adalimumab treatment. These results need to be confirmed in other observational studies.

Abstract PO4-14-02: Enhancing Informative Outcomes with Liquid Biopsy in a Real-World Population of Patients with Advanced Breast Cancer: Analysis of the SOLTI-1903 HOPE Study

Abstract Background: The integration of next-generation sequencing (NGS) into routine clinical practice is often hindered by financial and logistical challenges, resulting in diagnostic and therapeutic disparities among patients. Addressing these issues, the SOLTI-1903 HOPE study (NCT04497285) seeks to evaluate the feasibility of implementing a molecular screening program that actively involves patients with advanced breast cancer (ABC) in the management of their disease. By empowering patients, this study aims to gain a comprehensive understanding of the genomic landscape of ABC and to facilitate patient access to matched targeted therapies in Spain Methods: In the SOLTI-1903 HOPE study, a patient-centric approach was adopted, allowing patients living anywhere in Spain, and diagnosed with ABC, to actively lead their inclusion, participation, and follow-up using a digital tool (DT). Patients signed an informant consent, and then provided clinical information and underwent a liquid biopsy (LBx) using the Guardant360 panel at a local laboratory. LBx samples could be obtained at the moment of progressive disease (PD), when a new line of treatment was started &amp;lt; 8 weeks before extraction (PT), or during treatment with stable disease o partial response lasting more than 8 weeks (SD/PR). Clinical and molecular findings were evaluated by a Molecular Advisory Board (MAB), which generated a comprehensive report explaining the observed alterations and listing potentially beneficial matched targeted treatments. The primary endpoint of this subanalysis was to compare the genomic outcomes between LBx samples obtained at SD and those obtained at PD or PT. In the study, tissue samples were also collected and analysed by Foundation but this analysis will be reported in other communications. Results: From October 2020 to May 2023, a total of 273 blood samples were obtained from 253 patients diagnosed with ABC, with the majority being HR+/HER2- (81%), followed by HER2-positive (13%) and triple-negative (6%). Mean turnaround time was 10.9 days from blood collection to final result. Despite nearly 40% of patients being SD or PR, in 79.9% of the LBx (n=218), one or more genomic alterations were detected, and among these, 74.0% (n=202) were classified as pathogenic. Among the 74 genes analyzed by the Guardant360 panel, 8 genes were classified as tiers I-III according to the ESCAT levels of clinical relevance. In 150 LBx samples (54.9%), one or more pathogenic alterations were associated with ESCAT levels I-III, while only the remaining 52 LBx samples (19.1%) with pathogenic alterations were not associated with any ESCAT levels I-III. Among the analyzed LBx samples, a total of 928 distinct gene alterations were identified. Of these, 650 alterations (70.1%) were classified as pathogenic, while 278 (29.9%) were categorized as variants of unknown significance or lacked a reported impact. Notably, 25% (n=323) of the pathogenic gene alterations were further classified as ESCAT I-III. Out of the 273 LBx samples, 140 were obtained at PD, 30 at PT, and 103 at SD/PR. Circulating tumor DNA (ctDNA) was detected in 91.4% of PD samples, 86.7% of PT samples, and 62.1% of SD/PR samples (p&amp;lt; 0.001). Alterations classified as ESCAT levels I-III were observed in 70% of PD samples, 60% of PT samples, and 33% of SD/PR samples (p&amp;lt; 0.001). In 20 patients, LBx was repeated, with 16 of them having the first LBx obtained during SD/PR and the second LBx collected during PD or PT. The detection rate of ctDNA increased significantly from 18.7% (n=3) to 87.5% (n=14) (p&amp;lt; 0.001). The number of LBx samples with ESCAT levels I-III alterations also showed a significant increase from 12.5% (n=2) to 68.7% (n=11) (p=0.0032). Conclusions: Our findings highlight the importance of obtaining LBx samples during disease progression -compared to SD/PR- to gain greater genomic informativeness and better guide personalized treatment approaches for patients with advanced breast cancer. Citation Format: Tomás Pascual, Elia Seguí, Ruben Olivera-Salguero, Juan Miguel Cejalvo, Mafalda Oliveira, Pablo Tolosa, Maria Vidal, Marcos Malumbres, Joaquín Gavilá, Cristina Saura, Sonia Pernas, Rafael López, Mireia Margelí, Judith Balmaña, Montserrat Muñoz, Isabel Blancas, Valentina Boni, Eva Ciruelos, Elena Galve, Antonia Perelló, Rodrigo Sánchez-Bayona, Susana De La Cruz, Miguel De La Hoya, Aura Blanch-Torras, Rosana Sposito, Jordi Canes, Helena Masanas, Rosa Olmos, Margarita Forns, Maria José Prieto, Ana Casas, Aleix Prat. Enhancing Informative Outcomes with Liquid Biopsy in a Real-World Population of Patients with Advanced Breast Cancer: Analysis of the SOLTI-1903 HOPE 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 PO4-14-02.

Abstract PO4-05-04: Comparative effectiveness of Palbociclib plus Aromatase inhibitor versus fulvestrant alone as initial endocrine therapy for HR+/HER2- advanced breast cancer in Chinese clinical practice: a real-world study

Abstract Background: In the real world, there are still a large number of HR+/HER2- advanced breast cancer patients receiving initial endocrine therapy with fulvestrant monotherapy in China, especially patients with bone metastases only. It is due to lack of data comparing the effective between Palbociclib combined with AI and fulvestrant monotherapy as initial endocrine therapy. On the other hand, there are economic factors and access issues. According to the National Cancer Center's previous clinical experience, Palbociclib combined with AI is superior to fulvestrant monotherapy in HR+/HER2- advanced breast cancer patients receiving initial endocrine therapy. Therefore, we collected and summarized the previous clinical data in our center to compare the effective of Palbociclib combined with AI and fulvestrant monotherapy for HR+/HER2-advanced breast cancer patients receiving initial endocrine therapy in China. Patients and methods: This is a retrospective real-world study of multicenter studies. It aimed at verifying the effective of Palbociclib combined with AI and fulvestrant monotherapy for HR+/HER2-advanced breast cancer patients receiving initial endocrine therapy in China. A total of 392 patients with ≥3 months of follow-up received Palbociclib plus AI or fulvestrant alone in the first-line setting between April 1, 2015 and February 1, 2023. Stabilized inverse probability treatment weighting (sIPTW) was used to balance baseline demographic and clinical characteristics. Real-world progression-free survival (rwPFS) and overall survival (OS) were analyzed. Results: After sIPTW adjustment, a median follow-up of 37 months (range 34-40) in the Palbociclib group and 59 months (range 56-61) in those taking fulvestrant alone. Palbociclib combination regiment was associated with significantly longer median rwPFS compared to fulvestrant alone (22.0 vs 14.0 months; HR,0.469;95% CI 0.370–0.594, p&amp;lt; 0·0001). Median OS was not reached in the Palbociclib group and was 57 months (95% CI 54.0–66.0) in the fulvestrant group(HR,0.666; 95% CI 0.437–1.017, p&amp;lt; 0·94). Conclusion: In the real-world population of patients, palbociclib combined with AI endocrine therapy is superior to fulvestrant monotherapy in HR+/HER2- advanced breast cancer patients receiving initial endocrine therapy. PFS and OS before IPTW PFS and OS after IPTW Table patient characteristics Citation Format: Jian Yue, Xue Wang, Jie Ju, Zixiang Yang, Tong Wei, Peng Yuan, Min Gao, Ling Xu, Yin Guan. Comparative effectiveness of Palbociclib plus Aromatase inhibitor versus fulvestrant alone as initial endocrine therapy for HR+/HER2- advanced breast cancer in Chinese clinical practice: a real-world 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 PO4-05-04.