tbuckley/cabot-search huggingface dataset:
Rural-urban disparities in colorectal cancer-related mortality changes in the United States.
Authors: Laxman Yashwant Byreddi, Sundeep Atluri, Shiva Jashwanth Gaddam, Annapurna Pothuraju, Sri Lakshmi Pratyusha Javvadi, Vishal Devarkonda, Udhayvir Singh Grewal
Journal: Journal of Clinical Oncology (2024)

e13714 Background: Colorectal cancer is the second leading cause of cancer-related death in the world. The incidence of colorectal cancer rates is higher in rural areas compared to urban populations which is attributed to obesity, and lower adherence to screening. It is hence vital to identify large population-based data on rural and urban disparities in colorectal cancer-related mortality. We, therefore, sought to analyze the outcome variances between urban and rural populations. Methods: We retrieved the mortality data from the Centers for Disease Control and Prevention Wide-Ranging Online Data for Epidemiologic Research (CDC WONDER) multiple causes of death database (years:1999-2020) for patients aged 15 years and above, with malignant neoplasm of colorectum (ICD-10: C18.9, C19, C20) listed as underlying cause of death. We analyzed age-adjusted mortality rates (AAMRs) per 100,000 population and assessed temporal trends in the average percent change (APC) of AAMRs by applying the simplest model with a maximum of 3 joinpoints (using the Joinpoint regression program 5.0.2). We conducted nonparallel pairwise comparisons to assess differences in trends between large metropolitan, small/medium metropolitan, and rural areas (per National Center for Health Statistics Urban- Rural Classification Scheme, 2016) using average annual percentage change difference (AAPCD). Results: A total of 810,577 colorectal cancer-related deaths were retrieved, amongst which 418,744 (51.6%), were in the large metropolitan, 249,933 (30.8%) were in the small/medium metropolitan, and 141,900 (17.5%) were in the rural regions. We noted a decline in the AAMR overall and across large metropolitan, small/medium metropolitan, and rural areas. However, the decline in AAMR was significantly higher among large metropolitan areas as compared to rural areas (AAPCD: -1.0043, 95% CI -1.64, -0.35, p=0.0022). There was no statistically significant difference in decline in AAMR when large metropolitan areas were compared to small/medium metropolitan (AAPCD: -0.4517, 95% CI -0.90, -0.002, p=0.051) and when small/medium metropolitan were compared to rural areas (AAPCD: -0.5526, 95% CI -1.16, -0.05, p=0.07). Conclusions: We identified discrepancies in the decline in colorectal cancer AAMR between urban and rural areas. A substantially lower decline in AAMR is eminent in the rural regions, as compared to the large metropolitan counterparts. This raises the concern for poor access to cancer care in this population group. Our results emphasize the imperative of prioritizing and designing strategies to ensure healthcare equity in rural areas. [Table: see text]
Primary results from PATRICIA cohort C (SOLTI-1303), a randomized phase II study evaluating palbociclib with trastuzumab and endocrine therapy in pretreated HER2-positive and PAM50 luminal advanced breast cancer.
Authors: Eva Ciruelos, Tomás Pascual, Guillermo Villacampa, Sonia Pernas, Rodrigo Sanchez-Bayona, Jose Juan Ponce-Lorenzo, Blanca Cantos Sanchez de Ibarguren, Santiago Escrivá-de-Romaní, Antonia Perello, Alvaro Montaño, Eduardo Martinez, Ana López González, Mireia Melé Olivé, Juan De La Haba, Javier Cortes, Mafalda Oliveira, Lorea Villanueva, Xavier Gonzalez, Patricia Villagrasa, Aleix Prat
Journal: Journal of Clinical Oncology (2024)

1008 Background: The PATRICIA trial (cohorts A-B) demonstrated that palbociclib plus trastuzumab (T) is safe and active in patients (pts) with T-pretreated HER2-positive Hormone Receptor-positive (HR+/HER2+) PAM50 Luminal advanced breast cancer (ABC). Here, we present the primary efficacy analysis of the randomized cohort C from the PATRICIA trial that compares the efficacy of palbociclib + T + endocrine therapy (ET) with treatment of physicians’ choice (TPC). Methods: PATRICIA (cohort C) is a randomized, open-label, phase II study conducted at 34 sites in Spain recruiting from August 2019 to August 2023. Pts with HER2+/HR+ and centrally tested PAM50 Luminal A or B intrinsic subtype ABC who had received at least one prior line of anti-HER2 based regimens were eligible. Pts were randomized 1:1 to Cohort C1 (Palbociclib 125 mg/day orally 3 weeks/1 week off + T + ET) or Cohort C2 (TPC, including T + any ET or chemotherapy (CT) + T, or T-DM1). The stratification factors were number of previous regimens for ABC and presence of visceral disease. The primary endpoint was progression-free survival (PFS). The trial was designed to recruit a total of 102 pts, having an 80% power with one-sided alpha=0.1 to detect a HR of 0.62 in favor of the palbociclib cohort. The study was closed after 73 pts were randomized due to slow recruitment. Results: At data cut-off, 264 pts were pre-screened, and 73 pts were randomized. Baseline pts characteristics are summarized in Table 1. In cohort C1, 50% of the pts received fulvestrant and 50% aromatase inhibitor as ET. In cohort C2, 37.1% of pts were treated with TDM-1, 45.7% with CT+ T, 11.4 % with ET + T and two pts withdrew their consent before starting the treatment. Palbociclib + T + ET was associated with longer PFS compared to TPC (median 9.1 vs 7.5 months, stratified HR=0.52 [95%CI 0.29-0.94]; two-sided p=0.031); 12-months PFS rates were 43.7% and 21.4%, respectively. The overall response rate was 18.9% (95% CI 8.6-35.7) in cohort C1 and 8.3% (95% CI 1.4-28.5) in cohort C2. Grade ≥3 adverse events occurred in 63.2% of pts in C1 and 45.5% in C2 cohort. The most frequent grade ≥3 adverse event in the experimental arm was neutropenia (55.3%). Conclusions: The combination of palbociclib, T and ET showed a statistically significant improvement in PFS in patients with previously treated PAM50 luminal A or B HER2+ advanced breast cancer, as compared to TPC. Clinical trial information: NCT02448420 . [Table: see text]
DESTINY-Breast07: Dose-expansion interim analysis of T-DXd monotherapy and T-DXd + pertuzumab in patients with previously untreated HER2+ mBC.
Authors: Fabrice Andre, Erika P. Hamilton, Sherene Loi, Carey K. Anders, Peter Schmid, Daniil Stroyakovskiy, Rafael Villanueva, Jose Luiz Pedrini, Dinesh Chandra Doval, Bogdan Zurawski, Shin-Cheh Chen, Sarice Renee Boston, Adam Konpa, Barbara Pierotti, Giulia Fabbri, Komal L. Jhaveri
Journal: Journal of Clinical Oncology (2024)

1009 Background: Trastuzumab deruxtecan (T-DXd) is approved for adult patients (pts) with HER2+ advanced/metastatic breast cancer (mBC) who received a prior anti-HER2–based regimen. DESTINY-Breast07 is a Phase 1b/2 multicenter, open-label, modular study exploring the safety, tolerability, and antitumor activity of T-DXd alone or in combination with other anticancer agents (NCT04538742). These results are from an interim analysis of the dose-expansion phase assessing T-DXd ± pertuzumab (P) as first-line (1L) treatment in HER2+ mBC. Methods: Pts had locally assessed HER2+ mBC with measurable disease and no or stable brain metastases. A disease-free interval of ≥12 months from (neo)adjuvant therapy was required; no prior therapy for mBC was allowed. Pts were stratified by hormone receptor and disease status (recurrent vs de novo), and PD-L1 expression. Pts received T-DXd 5.4 mg/kg intravenously (IV) every 3 weeks (Q3W) as monotherapy or in combination with P 420 mg IV Q3W, with an 840 mg loading dose. Primary endpoints were safety and tolerability; key secondary endpoints included objective response rate (ORR) and progression-free survival (PFS), per RECIST 1.1 by investigator. Results: Seventy-five pts were treated in the T-DXd module and 50 pts in the T-DXd + P module; median follow up was 19.2 months (range 8.7–29.2) and 20.6 months (range 13.3–26.7), respectively. Median age was 57 years in both modules. As of August 1, 2023, the most common adverse event (AE) was nausea (T-DXd, 70.7% [4.0% Grade 3]; T-DXd + P, 68.0% [0% Grade 3]). Diarrhea was reported in 34.7% (2.7% Grade 3) and 60.0% (6.0% Grade 3) of pts in the T-DXd and T-DXd + P modules, respectively. There were no Grade ≥4 nausea or diarrhea events. Adjudicated drug-related interstitial lung disease (ILD) / pneumonitis was reported in six (8.0%) and five (10.0%) pts in the T-DXd and T-DXd + P modules, respectively (all Grade ≤2). One non-treatment-related AE with outcome of death was reported in the T-DXd module (post-acute COVID-19 syndrome); none with T-DXd + P. The confirmed ORR was 77.3% (80% confidence interval [CI] 70.0, 83.6) with T-DXd and 82.0% (80% CI 73.1, 88.8) with T-DXd + P. PFS rate at 12 months was 77.3% (80% CI 69.0, 83.7) with T-DXd and 89.4% (80% CI 81.9, 93.9) with T-DXd + P. Conclusions: Safety profiles were consistent with the known profiles for T-DXd and P, with no Grade ≥3 ILD events. Early data showed promising efficacy in both modules. The DESTINY-Breast07 study is ongoing; analyses from the Phase 3 DESTINY-Breast09 clinical trial will provide definitive data on TDXd ± P in 1L HER2+ mBC. Clinical trial information: NCT04538742 . [Table: see text]
Disparities in access to antineoplastic immunotherapy and outcomes by insurance status: A nationwide analysis.
Authors: Saad Javaid, Kelly Frasier, Vivian Li, Julia Vinagolu-Baur, Nataly Ortega Yaguachi, Evadne Rodriguez, Olivia Del Castillo, Raquel Batista, Kenlee Jonas, Laura Palma
Journal: Journal of Clinical Oncology (2024)

e13523 Background: Immunotherapy has emerged as a pivotal component in the treatment of cancer, particularly owing to the progress made in targeted therapies. Our analysis aimed to quantify the disparities in access to immunotherapy and the associated outcomes. Methods: We used National Inpatient Sample data (2017-2020) to identify patients hospitalized with a primary diagnosis of antineoplastic immunotherapy, stratifying them by either Medicaid or private insurance. The aim was to determine disparities in the likelihood of immunotherapy across various demographic factors and differences in outcomes, such as mortality and healthcare resource utilization. Results: A total of 14,530 patients were hospitalized for antineoplastic immunotherapy, with 2,960 (20%) having Medicaid insurance and 7,760 (53%) having private insurance. Patients with Medicaid were younger than those with private insurance (17.22% vs 38.53%). Compared to Medicare, patients with private insurance were more likely to undergo immunotherapy (OR=2.65(2.31-3.04); p&lt;0.001), while those with Medicaid had decreased odds (OR=0.75(0.61-0.92); p=0.007). Older patients were less likely to undergo immunotherapy than younger patients (36-45: OR=0.69(0.56-0.85), p=0.001; 46-64: OR=0.7(0.59-0.82), p&lt;0.001; &gt;65: OR=0.48(0.4-0.59), p&lt;0.001). Compared to the White population, Hispanics (OR=1.3(1.12-1.51); p&lt;0.001) and patients of other races (OR=3.33(2.86-3.88); p&lt;0.001) had increased odds of undergoing immunotherapy, while Black patients had decreased odds (OR=0.43(0.35-0.53); p&lt;0.001).The individuals with the highest median income were found to have the highest likelihood of undergoing immunotherapy (&gt;$86,000, OR=2.23(1.92-2.59); p&lt;0.001), followed by those in the less income groups ($65,000-$85,999: OR=1.6(1.38-1.86), p&lt;0.001; $50,000-$64,999: OR=1.48(1.28-1.73), p&lt;0.001). Patients in medium-sized (OR=1.27(1.03-1.55); p=0.022) and large (OR=3.49(2.93-4.15); p&lt;0.001) hospitals were more likely to receive immunotherapy compared to those in small hospitals. Patients with Medicaid had a higher total hospitalization cost than those with private insurances (+$219,484(83,731-355,238); p=0.002). There was no observed difference in mortality rates among patients with Medicaid or private insurance who received immunotherapy (Medicaid: OR=0.86(0.1-6.98), p=0.88; Private: OR=0.67(0.11-3.96), p=0.66). Conclusions: The utilization of immunotherapy among Medicaid patients is found to be lower when compared to those with private insurance and Medicare. This disparity is also related to a higher overall cost of hospitalization in Medicaid patients. However, there was no difference in mortality between the different insurance types who received immunotherapy.
Efficacy and safety of DOACs versus LMWH for elderly patients with active cancer: A meta-analysis.
Authors: Alice Marinho, Maria Carolina Caldeira de Freitas, Gabriela Coelho Itaya, Larissa Maria Da Costa, Eduardo Lambert Fossen, Davi Said Gonçalves Celso, Andre Ferro, Yasmin Dias, Eduardo de Figueiredo Vissotto, Mariana De Souza
Journal: Journal of Clinical Oncology (2024)

e13776 Background: Anticoagulant treatment in patients with cancer aims to reduce the high risk of thromboembolism. Direct oral anticoagulants (DOACs) and low-molecular-weight heparin (LMWH) are currently approved for the treatment of cancer-related thrombosis. However, there is limited data comparing the efficacy and safety of these two antithrombotic therapies among elderly patients with cancer. Methods: PubMed, Embase, and Cochrane Central Register of Controlled Trials databases were systematically searched for studies comparing DOACs with LMWH in cancer patients with newly diagnosed venous thromboembolism (VTE) or pulmonary embolism (PE). Both solid tumors and hematologic malignancies were included. Outcomes of interest were recurrent VTE and major bleeding. Odds ratio (OR) with 95% confidence intervals (CI) were pooled with a random-effects model. Statistical analysis was performed with Review Manager 5.4.1. Heterogeneity was assessed using the I2 statistic and chi-squared test. Results: Four studies, three randomized controlled trials (RCTs) and one observational, were included. A total of 3,266 patients older than 65 years who underwent anticoagulation with DOACs (35%) or LMWH (65%) were incorporated in the analysis. There was no statistically significant difference between anticoagulation therapies for recurrent VTE (OR, 0.68; 95% CI, 0.41-1.11; p = 0.13; I² = 56%; Table) or major bleeding (OR, 1.18; 95% CI, 0.61-2.25; p = 0.08; I² = 60%; Table). Conclusions: Our findings suggest no statistically significant differences in recurrent VTE or major bleeding between DOACs and LMWH in elderly oncologic patients with newly diagnosed VTE or PE. Given the practical challenges of using LMWH, DOACs may be considered an alternative anticoagulation strategy for these patients. [Table: see text]
Primary health clinicians' attitudes towards liquid biopsy as diagnostic test for advanced lung cancer.
Authors: Danyon Lo, Jenny Wong, Rawiri Keenan, Annie N. M. Wong
Journal: Journal of Clinical Oncology (2024)

e13525 Background: Lung cancer remains a leading cause of cancer mortality globally. In New Zealand (NZ), lung cancer disproportionately affects our indigenous Māori population with both incidence and mortality being three times higher than NZ-Europeans. Incidence of endothelial growth factor receptor mutated lung cancer is two to three times higher in Māori, Pacific, and Asian people compared to NZ-Europeans. Diagnostic delays arise from tissue biopsy difficulties and a lack of standardization in molecular testing. These delays could potentially be reduced if testing was augmented by liquid biopsy (LB) at the outset of diagnosis. LB could be more accessible, faster, and lower cost compared to tissue biopsy. We aimed to evaluate primary health clinicians’ (PHCs’) attitudes towards use of LB for molecular testing and lung cancer diagnosis. Methods: A NZ national survey was conducted of PHCs. The online survey was distributed through PHC bulletins, newsletters, and social media. It was open to circulation between November 2023 to January 2024 and consenting clinicians completed this via REDCap. Descriptive analysis was performed and reported in aggregate. Results: Seventy-two PHCs responded with 58 complete responses. Respondents were 78% urban and 25% worked in practices of very low-cost access. Current diagnostic challenges reported include limited PHC appointments, poor access to imaging, and limited access to specialist care. Fast track diagnostic pathway to specialist care existed for 55% of respondents. 92% were initially unaware of LB for molecular testing. 79% were not comfortable with pre-test genetic counselling associated for this. Concerns raised about LB included subsequent patient access to secondary care and establishing a culturally appropriate pathway particularly for Māori. Some rural PHCs highlighted the potential of LB to complement existing procedures. Provided there were adequate training and funding for LB, 72% of respondents would be comfortable requesting LB and associated counselling. The most preferred types of training were PHC focused articles (70%), online clinical pathways (68%), webinar (61%), online course (51%), and in-person presentation (46%). Conclusions: Most PHCs were not familiar with LB for molecular testing but 72% supported these tests to be incorporated into current pathways. There is a need to develop culturally safe pathways with sufficient training and funding, in order to reduce health inequities.
Informing optimal treatment (tx) sequences for platinum-eligible patients with locally advanced or metastatic urothelial carcinoma (la/mUC) in the United States: Results of a clinical simulation modeling exercise.
Authors: Javier Sanchez Alvarez, Agnes Benedict, Eszter Tichy, Thitima Kongnakorn, Chiemeka Ike, Mairead Kearney
Journal: Journal of Clinical Oncology (2024)

e13514 Background: Platinum-based chemotherapy (PBT) followed by avelumab (AVE) as first-line (1L) maintenance for patients with nonprogressive disease (PBT ± AVE) is the standard of care in la/mUC. This study compared the overall survival (OS) and cost-effectiveness of the tx sequence of PBT ± AVE followed by enfortumab vedotin (EV) or other therapies, including immuno-oncology (IO), in second line (2L; ie, PBT + 2L EV/IO or PBT + AVE + 2L EV/IO) vs 1L EV + pembrolizumab (PEM) for PBT-eligible patients (PBTp) from a US commercial payer perspective. Methods: A partitioned survival model compared outcomes with PBT ± AVE and EV + PEM among PBTp. Inputs included progression-free survival and OS, time to tx discontinuation, adverse event (AE) incidence, and health utilities and costs. Efficacy inputs were sourced and extrapolated from patient data in JAVELIN Bladder 100 (data cut: Jun 4, 2021), AVENANCE real-world study (1), and published data (EV-302 trial). Safety data were sourced from US prescribing information. Drug, subsequent tx, disease management, and AE management costs (2023 USD) were calculated. The optimal tx sequencing scenario assumed 80% of patients starting PBT were eligible to receive AVE (2023 Flatiron data cut; (2)), 70% of patients progressing on PBT ± AVE would start 2L, and 70% of those would be eligible for EV. Outcomes included life-years (LYs), quality-adjusted LYs (QALYs), costs, and incremental cost-effectiveness ratio (ICER). Scenarios and probabilistic sensitivity analyses (PSAs) were conducted to assess uncertainty. Results: LY, QALY, costs, and ICER modeling outcomes are shown in the Table. Use of EV in 2L after PBT ± AVE is associated with 0.76 lower QALYs, but given the large cost saving, it represents a cost-effective use of resources at the $150,000/QALY willingness to pay (WTP) threshold. PSAs showed that PBT ± AVE is likely to be more cost-effective over a broad and relevant WTP threshold range ($0-500,000/QALY). Results were sensitive to drug acquisition costs and eligibility to receive AVE and 2L EV. Conclusions: Based on this simulation exercise, the use of 2L EV after PBT ± AVE achieves considerable survival benefit at substantially lower costs vs 1L EV + PEM in PBTp with la/mUC. Given the shift toward value-based care in oncology, such analyses are becoming increasingly relevant to guide clinical decision-making. There is a need to assess tx alternatives that balance healthcare costs while optimizing outcomes in patients with la/mUC. 1. Barthélémy et al, J Clin Oncol 2024;42[suppl 4]: Abstract 561. 2. Moon et al, J Clin Oncol 2023;41[suppl 16]: Abstract 4567. [Table: see text]
FIT as a population-based and financially viable method to screen underserved patients for colorectal cancer.
Authors: Christopher Grivas, Abraham Ifrah, Nikita Dahake, Manasa Vallabhaneni, Shelby McNeilly, Brianna Graham, Gabrielle Gillow, Rishabh Khatri, Claire Raab
Journal: Journal of Clinical Oncology (2024)

e13516 Background: Temple University Hospital (TUH) created an initiative to increase colorectal cancer (CRC) screening by administering fecal immunochemical tests (FIT) to the underserved population of Philadelphia. We hypothesize that this will increase the percentage of diagnostic colonoscopies performed compared to baseline in our fixed capacity colonoscopy suite and ultimately generate a higher reimbursement per colonoscopy. This potential revenue increase can help fund the infrastructure to administer a large quantity of FIT tests to the community and create a truly equitable population-based approach to CRC screening. Methods: 27,169 colonoscopies and their associated CPT codes from 2017-2022 performed at TUH were analyzed. 16 individual CPT codes were identified and categorized as either screening or diagnostic CPT codes. Reimbursement for each of the CPT codes was determined by the Medicare reimbursement per CPT code and used to determine the average reimbursement per screening CPT code and average reimbursement per diagnostic CPT code. A Monte Carolo simulation model was created using Palisades @Risk software to compare the reimbursements of FIT test prompted vs. non-FIT test prompted colonoscopies over a range of possible distributions of diagnostic CPT codes. Monte Carlo simulations model scenarios that incorporate uncertainties with the objective of providing a distribution of outcomes from the least likely to most likely outcomes. Results: The historical distribution of screening vs. diagnostic CPT codes at TUH is 31% and 69%, respectively, with an average Medicare reimbursement of $2,668 per colonoscopy. We have distributed 292 FIT tests, and 5 FIT test prompted colonoscopies have been completed with 7 associated CPT codes. The preliminary distribution of screening CPT codes vs diagnostic CPT codes is 29% and 71%, respectively, with an average reimbursement of $2,691. Lastly, we used a Monte Carlo simulation to run 10 separate simulations with 5000 iterations each to show the most likely reimbursement rates over a possible distribution of diagnostic colonoscopies (Table). Conclusions: Our preliminary data suggests FIT testing can offer three main benefits: 1) Expansion of the number of patients receiving CRC screening; 2) triage optimization of the fixed capacity colonoscopy suite by performing more diagnostic colonoscopies than screening colonoscopies to diagnose more colorectal pathologies; and 3) funding for a population based FIT testing campaign by utilizing the Medicare reimbursement delta from screening to diagnostic colonoscopies. [Table: see text]