tbuckley/cabot-search huggingface dataset:
Non-small cell lung cancer in women: Experience of the National Institute of Oncology of Rabat, Morocco.
Authors: Boutaina Cherkaoui, Ibrahim El ghissassi, Najwa Chebli, Samia El hilali, Hanane Inrhaoun, Hind Mrabti, Hassan Errihani
Journal: Journal of Clinical Oncology (2025)

e20633 Background: Lung cancer is the leading cause of cancer deaths worldwide; its incidence in the female population is increasing. The objective of this study was to describe the epidemiological, clinical, paraclinical, therapeutic and evolutionary profile of female patients with non-small cell lung cancer (NSCLC), and to research the predictive factors of better survival. Methods: A retrospective cohort study was carried out among women with NSCLC, diagnosed between January 2019 and December 2023, at the National Institute of Oncology, Rabat, Morocco. The diagnosis was proven by pathological analysis of biopsy. Statistical analysis was carried by Jamovi software version 2.5.3. Results: we collected 146 women (18.3%) with NSCLC, average age was 63.5 ± 12.3 years. The percentage of non-smokers, passive smokers and active smokers was 87.7%, 7.5% and 4.8% respectively. Cough (56.2%), chest pain (21.2%) and dyspnea (19.9%) were the major clinical signs. The common histological types were: adenocarcinoma (90.4%), squamous cell carcinoma (6.8%). Most patients 87%(127 cases) were diagnosed at stage IV according to the TNM classification 8th edition. The epithelial growth factor receptor (EGFR) mutation test performed in 79 female patients (54%) was positive in 28 patients (35.4%). The Anaplastic Lymphoma Kinase (ALK) mutation, which was sought in 65 patients (44%), was positive in six patients (9.2%). The search for the Reactive Oxygen Species (ROS1) mutation was performed in seven patients (4.7%), was positive in one case (14.2%). For Programmed Death-Ligand 1 (PDL 1) expression was &lt;50% in 57 patients (85%) and ≥50% was noted in 10 patients (15%).106 stage IV patients (72.6%) had received first-line palliative systemic treatment, including 89 cases (84%) who had received platinum-based chemotherapy (including 11 EGFR mutated) and 17 EGFR mutated (16%) received anti-EGFR treatment. The median overall survival (OS) was 17 months [12.23] and the median progression-free survival (PFS) was 11 months [6.12]. Median OS of EGFR-mutated patients treated in first-line with EGFR TKIs (Tyrosine kinase inhibitors) was similar compared with that of EGFR-mutated patients treated with platinum-based chemotherapy (25 months), and PFS in these patients was slightly longer but statistically non-significant compared with that of patients treated with platinum-based chemotherapy (9.5 months vs. 6.5 months, p=0.22). Conclusions: The population of women with NSCLC studied was characterized by non-smoking, adenocarcinoma histological type dominance, and a high percentage of EGFR mutations. The median PFS of patients treated with EGFR TKIs were slightly longer than the patients who received platinum-based chemotherapy. These results encourage us to perform EGFR mutation testing in all patients diagnosed with adenocarcinoma so that they can receive targeted therapy with EGFR TKIs.
Phase I/II study to evaluate the feasibility and efficacy of sequential abemaciclib and gemcitabine treatment in patients with retinoblastoma (Rb)-positive leiomyosarcoma (LMS) and dedifferentiated liposarcoma (DDLPS).
Authors: Elise F. Nassif Haddad, Khandan Keyomarsi, Heather Y. Lin, Alexander J. Lazar, Wei-Lien Wang, Charles Manning, Guofan Xu, Osama F Mawlawi, Lorraine Cheryl Pelosof, Kelly Hunt, Funda Meric-Bernstam, Neeta Somaiah
Journal: Journal of Clinical Oncology (2025)

TPS11583 Background: LMS and DDLPS are aggressive malignancies with limited effective therapies in the advanced setting. Approximately 50% of LMS and nearly all DDLPS retain functional Rb protein, suggesting sensitivity to cell cycle inhibition. Our preclinical studies have demonstrated that combining sequential abemaciclib, a selective CDK4/6 inhibitor that induces cell cycle arrest, followed by gemcitabine timed with synchronized cell cycle reentry, results in synergistic antitumor activity in Rb-positive sarcomas. Sequential administration of abemaciclib followed by gemcitabine enhances apoptosis, impairs DNA repair mechanisms, and induces sustained cell cycle arrest. Methods: This is a multicenter, open-label, phase 1/2 clinical trial conducted through the National Cancer Institute (NCI), enabling broad, nationwide patient enrollment. The phase 1 dose-escalation portion will determine the maximum tolerated dose and recommended phase 2 dose of sequential abemaciclib and gemcitabine in patients with advanced/metastatic soft-tissue sarcomas. Part A of phase 1 will use biomarkers of cell cycle (functional positron emission tomography imaging using [18]F-fluoro-3'-deoxy-3'-L-fluorothymidine and thymidine kinase activity) to determine the optimal schedule of sequencing. Part B of the phase 1 will follow the BOIN design. Eligible patients must have histologically confirmed LMS or DDLPS with Rb positivity confirmed by immunohistochemistry, measurable disease, ECOG performance status ≤2, and adequate organ function. Prior gemcitabine therapy is permitted in phase 1 but excluded in phase 2. Phase 1 Part A is restricted to MD Anderson only enrollment due to the requirements of biomarker integration and timing. In the randomized phase 2 portion, patients will be randomized 1:1 (stratified by DDLPS vs LMS) to receive either (1) sequential abemaciclib followed by gemcitabine or (2) gemcitabine and docetaxel. The primary endpoint is progression-free survival, with secondary endpoints including objective response rate, overall survival, and safety. Correlative studies will analyze tumor biopsies and blood samples collected at baseline, after two treatment cycles, and at disease progression. Biomarker analyses will include RB1 expression profiling, whole exome sequencing, RNA sequencing, and circulating tumor DNA. Clinical trial information: NCT06498648 .
The impact of obesity on survival in non-small cell lung cancer patients receiving immune checkpoint inhibitor therapy: A retrospective multi-institutional US cohort study.
Authors: Mostafa Eysha, Mohanad Elchouemi, Arsalaan Asad, Sharda Singh, Thomas E. Hutson, Jose Conejo-Garcia
Journal: Journal of Clinical Oncology (2025)

e20630 Background: Immune checkpoint inhibitor (ICI) therapy is a cornerstone in the treatment of metastatic non-small cell lung cancer (NSCLC). However, many patients develop resistance or fail to respond to ICI. There has been a lot of interest in studying the host factors that might influence the response to immunotherapy. In recent years, the Obesity paradox phenomenon has been studied in multiple cancers. However, there is scarce information on the impact of obesity on the various ICI therapies on NSCLC patients in the US. In this study, we are presenting the first real-world analysis of the effect of obesity on survival in US based patients diagnosed with metastatic NSCLC and receiving ICIs. We also tried to unveil any possible underlying mechanisms that might explain this phenomenon like complications and immune‐related adverse events (irAEs). Methods: Data was retrospectively collected from the independent US population-based TriNetX network, a national electronic health record database with 120 million US patients from over 70 healthcare organizations. We identified patients ≥ 18 years old with non-small cell lung cancer diagnosis who received ICI therapy between 2012 and 2024. ICI therapies included pembrolizumab, nivolumab, atezolizumab, durvalumab, ipilimumab and cemiplimab. Patients were then split into two cohorts: those with normal BMI (18.5-24.9) and obese BMI (≥30). Patients were then 1:1 propensity score matched based on age, sex, race, ethnicity, type of ICI therapy used, comorbidities and staging. Overall survival (OS), NSCLC related complications and irAEs were measured at 6 months, 1 year and 3 years after initiation of ICI treatment. Results: We identified 10,056 patients over the age of 18 who received ICI therapy for NSCLC. After 1:1 matching, each cohort in our analysis included 2762 patients. In the normal and obese groups mean age in both groups was 66.2 ± 10.8 and 66.3 ± 9.69 years respectively. Patients were also more likely to be white (73%) and male (49%) in both groups. Obesity BMI was associated with significantly improved OS at 6 months (hazard ratio [HR], 0.78 [95% CI, 0.66-0.83]), 1 year (HR, 0.81 [95% CI, 0.74-0.89]), and 3 years (HR, 0.88 [95% CI, 0.81-0.95]) after ICI treatment, compared with patients with normal BMI. There was no difference in rates of NSCLC specific complications or irAEs at any of the time points from 6 months to 3 years. Conclusions: Analysis of one of the largest US based databases showed that obesity is associated with better overall survival without significant difference in complications or irAEs which suggest that the difference in the survival is likely due to the direct effect of the obesity on the cancers. Further clinical trials and transitional studies should be geared towards investigating the effects of obesity on tumor microenvironment.
The preliminary safety results of an observational phase II study of concurrent use of aspirin with dabrafenib and trametinib in BRAF V600 NSCLC.
Authors: Rui Han, Jianghua Li, Yong He
Journal: Journal of Clinical Oncology (2025)

e20632 Background: Dabrafenib combined with trametinib (DabTram) is highly effective in treating BRAF V600-mutant non-small cell lung cancer (NSCLC). However, pyrexia is the most common adverse event (AE), affecting over 50% of patients and often leading to dose reductions or interruptions, significantly impacting clinical application. Aspirin, a COX inhibitor, not only reduces PGE2 to alleviate pyrexia but may also modulate resistance pathways involving PI3K-AKT-mTOR and RAS-RAF-MEK, providing additional therapeutic benefits. This study evaluates the safety and potential of concurrent aspirin use with DabTram in this population (NCT05988697). Methods: This multicenter phase II study enrolled IIIB-IV stage BRAF V600-mutant NSCLC patients between May 2023 and November 2024 across hospitals in Chongqing, China. Patients received Dabrafenib 150 mg BID, Trametinib 2 mg QD, and Aspirin 100 mg QD until progression or intolerable toxicity. Primary endpoints were progression-free survival (PFS) and pyrexia incidence. Secondary endpoints included overall response rate (ORR), disease control rate (DCR), overall survival (OS), and coronary event risk. Results: Seventeen patients (median age: 67 years; 64.7% male; 100% stage IV adenocarcinoma) were enrolled. Most (58.8%) were ex-smokers, and 41.2% had prior systemic anti-cancer therapy. After a median follow-up of 8.2 months, treatment-related AEs (TRAEs) occurred in 35.3% of patients, including pyrexia (11.8%), hiccups (5.9%), rash (5.9%), fatigue (5.9%), and oral ulcers (5.9%), all grade 1/2. Pyrexia, typically affecting over half of DabTram-treated patients, was reported in only 2 patients (1 grade 1, 1 grade 2), significantly lowering its incidence. One patient required dose reduction, and no gastrointestinal bleeding or grade ≥3 AEs were observed. Conclusions: The addition of aspirin to DabTram therapy effectively reduced the incidence of pyrexia, the most frequent AE limiting DabTram use, and minimized treatment interruptions. This innovative approach demonstrated a favorable safety profile with no new signals. Longer follow-up is needed to confirm survival benefits in BRAF V600-mutant NSCLC patients. Clinical trial information: NCT05988697 . Baseline characteristics. Demographic variable N=17(%) Median Age (min-max) 67(48-80) Sex: Female/Male 6(35.3)/11(64.7) Smoking history: Never smoked/ Ex-smoker 7(41.2)/ 10(58.8) Histology: Adenocarcinoma 17(100) Disease stage: IV 17(100) Prior systemic anti-cancer therapy: Yes/No 7(41.2)/ 10(58.8)
Evaluating the Khorana score in advanced EGFR-mutated NSCLC patients receiving first-line osimertinib.
Authors: Amin Benyounes, Melissa Yacur, Najeebah A. Bade, Shubha Srinivas
Journal: Journal of Clinical Oncology (2025)

e20634 Background: Venous thromboembolism (VTE) poses a significant risk in patients with non-small cell lung cancer (NSCLC), particularly those with driver mutations, such as in the Epidermal Growth Factor Receptor (EGFR). While the Khorana Score is commonly used to predict VTE risk in general oncology patients, its relevance in genetically defined subgroups, such as EGFR-mutated NSCLC patients, remains unclear. Methods: This retrospective study evaluated the correlation between the Khorana Score and VTE incidence in 47 advanced EGFR-mutated NSCLC patients receiving first-line osimertinib at the Inova Schar Cancer Institute. Baseline demographics and Khorana Score components, including platelet count, white blood cell count, body mass index, hemoglobin, and erythropoietin stimulating agent use, were recorded, with VTE incidence as the primary outcome. Results: VTE was observed in 19.1% of patients, but the Khorana Score did not significantly correlate with VTE development. Median progression-free survival (PFS) was 13.87 months in the VTE group compared to 9.9 months in those without VTE. Conclusions: Our findings suggest that the Khorana Score may not be a reliable predictor of VTE risk in EGFR-mutated NSCLC patients treated with osimertinib, likely due to its design for a more heterogeneous cancer population. Further research is warranted to develop tailored VTE risk models for this distinct patient subgroup.
Geographic, racial and temporal disparities in cancer and respiratory failure mortality in the US: A 24 year retrospective study.
Authors: Aqsa Komel, Abdul Qadeer, Sardar Muhammad Imran Khan, Muneeb Khawar, Muhammad Waqas, Azka Aisha, H Muhammad Ismail Mughal, Salman Hassan, Mian Zahid Jan Kakakhel, Mobeen Zaka Haider, Aamir Laghari, Robert W. Kirchoff, Allahdad Khan, Adnan Safi
Journal: Journal of Clinical Oncology (2025)

e20520 Background: Cancer and respiratory failure (RF) are amongst leading causes of mortality in adults. This study investigates national trends in age-adjusted mortality rates (AAMRs) for cancer and RF in the United States from 1999 to 2023, focusing on disparities by gender, race, region, and rural-urban residence to inform public health strategies. Methods: This descriptive study analyzed data from the CDC WONDER database, of adults aged 25 and older. Mortality data were identified using ICD-10 codes C00–C97 (cancer) and J96 (RF). AAMRs per 100,000 population were calculated and stratified by gender, race/ethnicity, census region, urban-rural classification, and state. Temporal trends were analyzed using Joinpoint regression to estimate annual percent changes (APCs) with 95% confidence intervals (CIs). Statistical significance was set at p &lt; 0.05. Results: From 1999 to 2023, total deaths of 1,263,368 attributed to cancer and RF (682,141 men, 581,227 women). AAMRs declined from 1999 to 2004 (APC = -1.5, 95% CI: -4.0 to -0.4), stabilized from 2004 to 2012 (APC = 0.8, 95% CI: 0.1 to 2.4), and increased from 2012 to 2023 (APC = 3.2, 95% CI: 2.9 to 3.8). Men experienced a greater initial decline (APC = -2.1, 1999–2004) but significant increases thereafter (APC = 3.0, 2012–2023), while women showed a slower decline followed by sharper increases (APC = 3.5, 2013–2023). Non-Hispanic Black populations initially declined (APC = -1.7, 1999–2003) but later increased significantly (APC = 3.0, 2014–2020). Hispanic/Latino populations declined (APC = -1.2, 1999–2009) before rising sharply (APC = 3.1, 2009–2020). American Indian or Alaska Native populations showed consistent increases (APC = 1.7, 1999–2020). Urban areas experienced initial declines (APC = -1.7, 1999–2004), followed by increases (APC = 2.4, 2011–2020). Non-metropolitan areas exhibited steeper increases (APC = 4.6, 2014–2020). Regionally, the West recorded the highest AAMR (24.0), followed by the Northeast (23.6), South (20.9), and Midwest (18.0). Mississippi had the highest state-level AAMR (36.3), while Wisconsin had the lowest (10.0). States in the top 90th percentile included Mississippi, Arkansas, and California, while Wisconsin, Minnesota, and Oregon were among the lowest. Conclusions: Cancer and RF mortality declined initially but have significantly increased in recent years. Disparities persist across gender, racial, and regional groups, underscoring the need for focused public health efforts and equitable resource distribution to address these trends.
Myocarditis in patients with non-small cell lung cancer treated with immune checkpoint inhibitors: A multicenter study.
Authors: Adnan Saifuddin, Shanawar Ali Waris, Nanda Siva, Nolan Holley, Yashan Thakkar, Salah Ud Din Safi
Journal: Journal of Clinical Oncology (2025)

e20626 Background: Immune checkpoint inhibitors (ICIs) have improved survival in patients with lung cancer; however, their association with immune-related adverse events remains a significant challenge. While rare, ICI-related myocarditis can pose high mortality risk. There is a lack of comprehensive real-world data in the literature on ICI-related myocarditis. Methods: A retrospective cohort study was conducted using TriNetX, a combined claims and electronic health record database of more than 100 healthcare organizations. Patients with non-small cell lung cancer (NSCLC) treated with ICIs were compared to a 1:1 propensity score-matched cohort of patients treated with chemotherapy or targeted therapies. Primary outcomes included attributable risk of myocarditis, mortality, and ICU level care. ICI-associated myocarditis was defined as acute myocarditis occurring within 12 months of initiating ICI therapy. Within the ICI cohort, patients who developed myocarditis were compared to patients who did not develop myocarditis for the presence of major adverse cardiovascular events (MACE), as defined by myocardial infarction (MI), heart failure (HF), or stroke. Results: A total 44,263 non-small cell lung cancer patients who underwent ICI therapy were identified of whom 64 developed ICI-myocarditis. After propensity score matching, the risk of myocarditis attributable to immune checkpoint inhibitors (ICIs) compared to control group treated with chemotherapy/targeted therapies was 0.116% (95% CI, 0.076% to 0.156%) in the first year of therapy. ICI group had no increased risk of requiring critical care services (RR 1.027 (95% CI, 0.991 to 1.065) and had decreased mortality risk at one year (HR 0.909 [95% CI, 0.887 to 0.932]) and five years (0.969 [95% CI, 0.950 to 0.988]), compared to the control group. Within the ICI group, patients that developed myocarditis had a significantly higher risk of major adverse cardiovascular events (MACE) at one year compared to ICI patients that did not develop myocarditis (RR 3.740 [95% CI, 3.167 to 4.417]). Specific cardiovascular events also demonstrated significantly higher risks in the ICI myocarditis group including MI (RR 6.649 [95% CI, 4.672 to 9.464]), HF (RR 4.445 [95% CI, 3.526 to 5.603]), and stroke (RR 3.197 [95% CI, 1.807 to 5.658]). Conclusions: This large multicenter retrospective cohort study of patients with NSCLC from across the USA demonstrates that the risk of myocarditis is marginally higher compared to patients receiving chemotherapy or targeted therapies. Patients who developed ICI-associated myocarditis had a substantially higher risk of MACE, including myocardial infarction, heart failure, and stroke, compared to those receiving ICIs without myocarditis. These findings emphasize the need for careful monitoring of cardiovascular health in patients receiving ICIs.
A phase 3, randomized, double-blind, placebo-controlled study to assess the efficacy and safety of emactuzumab in patients with tenosynovial giant cell tumor (TANGENT).
Authors: Hans Gelderblom, Emanuela Palmerini, Jean-Yves Blay, Michiel van de Sande, Javier Martin Broto, Raul Terés, Madhu Davies, Elyse Seltzer, Sander Veltkamp, Gabriel Tinoco
Journal: Journal of Clinical Oncology (2025)

TPS11584 Background: Tenosynovial giant cell tumor (TGCT) is a rare, non-malignant, locally aggressive tumor of the synovium, primarily affecting knee, hip, and ankle joints. TGCT is caused by excessive production of colony stimulating factor 1 (CSF-1), a cytokine involved in the proliferation, differentiation, and survival of monocytes and macrophages. It is a chronically debilitating disease, causing pain, stiffness, loss of function in the affected joints and a decline in quality of life. The worldwide incidence in digits, localized, and diffuse TGCT is about 29, 10, and 4 per million person-years, respectively. Surgery remains the principal treatment option, at the cost of a high rate of tumor recurrence, and risk of damage to the affected joint and surrounding tissues. Systemic treatment options are limited. Emactuzumab is a novel monoclonal antibody, and potent and specific CSF-1 receptor (CSF-1R) antagonist, that causes apoptosis of M2-type macrophages in the tumor micro-environment, thereby inhibiting tumor growth. In a phase Ia/b study, emactuzumab was administered i.v. at doses varying from 900-2000 mg (cycles ranging 1-14) in advanced diffuse TGCT patients (Cassier et al, EJC, 2020). Emactuzumab was well tolerated and showed rapid and pronounced responses with an objective response rate (ORR) of 71%, which was durable with an ORR of 70% and 64% after one or two years, respectively. Clinical activity was associated with symptomatic improvement. The optimal biological dose of emactuzumab, defined as 1000 mg q2w, is under investigation in the Phase 3 trial. Emactuzumab was granted an Orphan Drug Designation by the European Medicines Agency in March 2022. Methods: TANGENT (NCT05417789) is a randomized, double-blind, placebo-controlled trial designed to confirm the efficacy and safety of emactuzumab in TGCT patients not amenable for surgery. The primary endpoint is efficacy, assessed as ORR at 6 months by MRI per RECIST v1.1. Key secondary endpoints include patient-reported outcomes (PROMIS-PF), range of motion, pain and stiffness, and other antitumor activity (e.g. TVS). In Part 1, subjects will be randomized 2:1 to receive either emactuzumab 1000 mg or placebo i.v. q2w for 5 doses over 10 weeks, followed by an observation period of 3 months. Part 2 is a follow-up phase from 6-24 months post randomization during which subjects whose TGCT worsens may be eligible for emactuzumab. The study is actively recruiting. Assessments include tumor evaluation, physical examination, vital signs, electrocardiograms, questionnaires, urinalyses, and blood tests for hematology, biochemistry, and PK of emactuzumab. Safety will be assessed by laboratory assessments and evaluation of adverse events. Clinical trial information: NCT05417789 .