tbuckley/cabot-search huggingface dataset:
Sex differences in toxicities and survival outcomes among patients with stage III colorectal cancer receiving adjuvant fluoropyrimidine monotherapy: A pooled analysis of four randomized controlled trials (JCOG2310A).
Authors: Hidekazu Hirano, Kozo Kataoka, Toshifumi Yamaguchi, Anna Dorothea Wagner, Yasuhiro Shimada, Masafumi Inomata, Tetsuya Hamaguchi, Yasumasa Takii, Junki Mizusawa, Yusuke Sano, Akio Shiomi, Manabu Shiozawa, Masayuki Ohue, Tomohiro Adachi, Hideki Ueno, Satoshi Ikeda, Koji Komori, Shunsuke Tsukamoto, Atsuo Takashima, Yukihide Kanemitsu
Journal: Journal of Clinical Oncology (2025)

116 Background: Fluoropyrimidine agents are the key component of adjuvant chemotherapy for pathological stage III colorectal cancer (CRC). Western studies have shown that female sex is associated with favorable survival outcomes after surgery, yet a risk factor for fluoropyrimidine-related adverse events (AEs) during adjuvant chemotherapy. However, it remains unclear whether there are sex differences in the treatment outcomes in this setting among the Japanese population. Methods: Patients enrolled in four randomized controlled trials (JCOG0205, JCOG0404, JCOG0910, and JCOG1006) who received adjuvant fluoropyrimidine monotherapy for pathological stage III CRC were analyzed. Incidences of AEs and survival outcomes (relapse-free survival [RFS], and overall survival [OS]) were compared between males and females. Multivariable logistic regression analyses were performed to evaluate associations between sex and the development of AEs. Multivariable Cox regression analyses were performed using Cox proportional hazard models to evaluate associations between sex and survival outcomes. Results: A total of 3170 patients (male, n = 1654; female, n = 1516) were included in the analysis. Compared with male patients, female patients were more likely to require dose reduction (male, 20.4%; female: 28.8%, p &lt; 0.0001) and had low completion proportions of adjuvant chemotherapy (male, 81.7%; female, 77.0%, p = 0.0011). Female patients experienced higher incidences of any-grade hematological and non-hematological AEs (Table). Female sex was associated with higher incidences of grade 3/4 hematological AEs (odds ratio [OR]: 1.702 [95% CI 1.272–2.278], p = 0.0003) and non-hematological AEs (OR: 1.666 [95% CI 1.373–2.020], p &lt; 0.0001). Female sex was identified as a favorable prognostic factor for RFS (hazard ratio [HR]: 0.729 [0.627–0.848], p &lt; 0.0001) and OS (HR: 0.796 [0.653–0.970], p = 0.0238). Conclusions: Sex differences had implications for the development of AEs and survival outcomes of Japanese patients with pathological stage III CRC who received adjuvant fluoropyrimidine monotherapy. Incidences of adverse events. Adverse event Any grade Grade 3/4 Male% (95% CI) Female% (95% CI) p-value Male% (95% CI) Female% (95% CI) p-value Any hematological toxicity 63.7 (61.3–66.0) 83.9 (82.0–85.8) &lt;0.0001 5.0 (4.0–6.1) 8.9 (7.5–10.4) &lt;0.0001 Any non-hematological toxicity 93.3 (92.0–94.5) 96.1 (95.0–97.0) 0.0006 13.3 (11.7–15.1) 20.8 (18.8–22.9) &lt;0.0001
Durvalumab (DUR) effectiveness in advanced biliary tract cancer (aBTC) patients based on real-world data evidence.
Authors: Jesus Rodriguez-Pascual, Gema Hernández, Lisardo Ugidos, Alejandro Parralejo, Juan Diego Rodriguez-Castaño, Juan Jose Serrano, Angel Ayuso
Journal: Journal of Clinical Oncology (2025)

598 Background: Based on TOPAZ-1 trial, Durvalumab (DUR) plus gemcitabine and cisplatin significantly improved overall survival (OS) in advanced biliary tract cancer (aBTC) patients. Real-World data evidence can evaluate the benefit of this combination outside controlled studies comparing patients treated with standard chemotherapy with or without DUR. Methods: Using the TriNetX Global Collaborative Network, a platform that operates globally based on anonymized and aggregated clinical data, a sample of aBTC patients from 128 healthcare organizations (HCOs) who met the initial criteria was selected. 5-year overall survival (OS) was analyzed between these cohorts using a Kaplan-Meier analysis. Hazard Ratio (HR) and its 95% confidence interval (95%CI) were calculated to evaluate the difference between cohorts. Propensity Score Matching (PSM) was used to balance the cohorts based on age, gender, and race mitigating possible cofounding variables. All statistical analyses were conducted utilizing the TriNetX Analytics function in the online research. Results: A total of 1099 patients met the study criteria and were included in our study. 399 received DUR plus chemotherapy and 700 received only chemotherapy. Patients treated with DUR showed a significant better OS compared to patients treated with only chemotherapy, both previous to PSM and before PSM (post-PMS median OS 418 days vs 359 days, HR 0.862, 95%CI 0.759-0.979, p=0.022). Conclusions: This is the largest World-Real Data study exploring the effectiveness of Durvalumab in aBTC patients outside clinical trials, confirming a similar benefit than TOPAZ-1 study.
Efficacy and safety of HER2-targeted therapies in biliary tract cancer: A systematic review and meta-analysis of early phase clinical trials.
Authors: Parth Sharma, Mangesh Kritya, Priyanka Sharma, Vasu Bansal, Marc Thomas Roth
Journal: Journal of Clinical Oncology (2025)

599 Background: Biliary tract cancers (BTC) are a rare type of gastrointestinal malignancy, often presenting in advanced stages and associated with a dismal prognosis. BTC are frequently resistant to conventional chemotherapy, with novel targeted therapies playing a pivotal role in overcoming this challenge. HER2 has recently emerged as an important actionable target in patients with BTC. We aim to evaluate the efficacy and safety of HER2 -directed monoclonal antibodies (MOAs), bispecific antibodies, antibody-drug conjugates (ADCs), and their combinations in BTC. Methods: A systematic literature search was conducted on PubMed, Embase, and Cochrane Central Register of Controlled Trials for clinical trials investigating HER2 -directed MOAs, bispecific antibodies, ADCs, and their combinations in BTC. The study was conducted following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) Guidelines. A random effects model was used to pool the outcomes along with 95% confidence intervals (CI). Statistical analyses were performed using program R version 4.4.1. Results: We included 12 clinical trials with three Phase I and nine Phase II trials. The pooled ORR (objective/overall response rate) was 35.5% (95% CI: 26.2-45.3, I 2 : 69%), and the DCR (disease control rate) was 72.2% (95% CI: 65.3-78.8, I 2 : 37%). The median follow-up period for DCR was four months. Trastuzumab, in combination with gemcitabine-cisplatin as first-line therapy, had the highest median progression-free survival of 7 months (95% CI: 6.2-7.8), whereas the combination of trastuzumab and tucatinib had the longest median overall survival 15.5 months (90% CI: 6.5-16.7) reported. The most common treatment-related ≥grade 3 adverse events reported across the cohort were anemia and neutropenia. Three cases of confirmed grade 5 interstitial lung disease were reported in patients who received trastuzumab deruxtecan. Clinical trials included in this study are summarized in the table. Conclusions: Advances in precision oncology and the emergence of novel targeted therapies have revolutionized cancer management. HER2 -directed therapies have shown promising results for patients inflicted with BTC having HER2 alterations in the early phase clinical trials. Further larger studies are awaited to explore the efficacy of HER2 -directed therapies in BTC. Clinical trials of HER2 -directed therapies in BTC. HER2-directed therapy Number of clinical trials Total number of BTC participants ORR, in % (95% CI) DCR, in % (95% CI) Trastuzumab + chemo 2 124 43.2 (19.4-68.8) 80 (72.3-86.7) Trastuzumab + pertuzumab 2 45 20.9 (9.1-35.3) 53.4 (37.8-68.8) Trastuzumab deruxtecan 4 84 27.2 (6.9-52.6) 71.9 (58.4-84) Trastuzumab + tucatinib 1 30 46.7 (28.5-65.5) 76.7 (57.7-89.7) Zanidatamab 2 101 40.5 (30.9-50.4) 67.6 (57.9-76.6) SHR-A1811 1 16 56.3 (29.9-80.2) 81.3 (54.4-96)
Neoadjuvant immune checkpoint blockade in resectable hepatocellular carcinoma: A systematic review and meta-analyisis.
Authors: Luís Felipe Leite da Silva, Luiz F. Costa Almeida, Anelise Poluboiarinov Cappellaro, Mariana Macambira Noronha, Marcos Belotto, Renata D'Alpino Peixoto
Journal: Journal of Clinical Oncology (2025)

590 Background: Hepatocellular carcinoma (HCC) presents a significant therapeutic challenge due to its high recurrence rates after curative-intent resection. Neoadjuvant immune checkpoint blockade (ICB) has emerged as a promising strategy to improve tumor control by modulating the immune microenvironment prior to surgery. This systematic review and meta-analysis aim to assess the safety and efficacy of neoadjuvant ICB in improving clinical outcomes for patients with resectable HCC. Methods: A systematic search of PubMed, EMBASE, and Cochrane databases was conducted to identify clinical trials examining neoadjuvant ICB in resectable HCC. Primary endpoints included pathological complete response (pCR), major pathological response (mPR), overall response rate (ORR), and grade 3-4 treatment-related adverse events (TRAE). Prespecified subgroup analyses were conducted for studies combining ICB with tyrosine kinase inhibitors (TKIs) or dual ICB therapies. Pooled proportions were calculated using a random-effects model via the R package "meta." Inter-study heterogeneity was assessed using the I² statistic and test for subgroup differences were conducted. Results: Out of 1,321 studies screened, 14 clinical trials involving 252 patients with resectable HCC were included. Most studies were phase II trials (57%), and patient median age ranged from 57.5 to 68.0 years, with 88.3% of patients being male. The pooled prevalence of mPR was 32% (95% CI, 24–42%; I² = 9%)while pCR was achieved in 24% (95% CI, 17–34%; I² = 29%)of patients. The ORR was 27% (95% CI, 18–39%; I² = 49%), and severe adverse events (grade 3-4 TRAE) had a pooled prevalence of 24% (95% CI, 17–34%; I² = 16%). Subgroup analysis of trials combining ICB with TKIs showed an ORR 34% (95% CI, 20–55%; I² = 60%), an mPR rate of 27% (95% CI, 19–40%; I² = 0%), and a pCR rate of 20% (95% CI, 14–30%; I² = 0%). Dual ICB therapies demonstrated a higher mPR rate of 42% (95% CI, 26–67%; I² = 16%) and a pCR rate of 41% (95% CI, 29–59%; I² = 29%), but were associated with a higher incidence of severe TRAE (41%; 95% CI, 29–60%; I² = 0%). Conclusions: Neoadjuvant ICB demonstrates promising efficacy in resectable HCC, particularly when combined with TKIs or dual ICB therapies. While dual ICB enhances pathological response rates, it is associated with higher rates of severe TRAE. These results highlight the need of further studies to optimize combination strategies that balance efficacy and safety for patients with resectable HCC.
The Gastric Cancer Registry: A multi-omic cellular and molecular resource for cancer biomarker and therapeutic discovery.
Authors: Hanlee P. Ji, Rithi Meka, Ignacio Wichmann Perez, Susan M. Grimes, Hojoon Lee, Yan Wang, Anuja Sathe
Journal: Journal of Clinical Oncology (2025)

491 Background: The Gastric Cancer Registry (GCR) is a comprehensive clinical and genomic data resource focused on gastric cancer (GC) patients and individuals with a family history of GC or a germline CDH1 mutation. As part of the GCR’s ongoing enrollment, patients contribute cancer history information, archival tumor samples and other biospecimens. The cancer samples undergo extensive molecular and cellular analysis that includes genomic sequencing and spatial analysis. We have generated a robust dataset, publicly accessible online through the GCR Genome Explorer (GCR-GE). This genomic, molecular and cellular resource provides a rich data set that accelerates multidisciplinary research aimed at improving detection and treatment strategies for GC. GC disproportionately affects Latin American populations - we have included new cohorts from Latin America. The GCR enables researchers, clinicians and patients to address specific questions about the molecular and cellular basis of GC. Methods: GC samples underwent whole genome, whole exome, and bulk RNA sequencing were conducted. The genomic features identified include copy number variation, gene mutations, gene expression, microbiome composition, estimation of tumor-infiltrating immune cells, tumor neoantigens, MSI/MSS status, and HLA subtypes. In addition to genomic data, clinical data was compiled from survey responses and pathology reports and integrated into the GCR-GE. We have incorporated single cell and spatial analysis that includes diverse cell types, single cell gene expression and cellular architecture in native tumor tissues. This data was released to the GCR Genome Explorer website. Results: A total of 817 subjects have enrolled in the GCR including 598 diagnosed with GC and 219 at high-risk for GC through family history of GC and/or a CDH1 mutation. Of the 598 with GC, some met multiple criteria including at least 40 with a family history of GC, 10 with a CDH1 mutation, and 18 with both a family history of GC and a CDH1 mutation. The GCR-GE includes data from 257 gastric tumors in addition to external datasets from TCGA. In the latest data release, clinical and genomic data from 78 gastric tumors from patients in Latin America were integrated into the GCR-GE. Conclusions: The GCR is a comprehensive database of crucial clinical and genomic data necessary for driving forward GC research. Through global expansion, the GCR has generated a more representative dataset by increasing racial diversity and including underrepresented populations that are at higher risk for GC.
Characterization of the real-world first line (1L) use of single dose tremelimumab regular interval durvalumab (STRIDE), for treatment of unresectable hepatocellular carcinoma (uHCC), using two electronic medical record (EMR) databases.
Authors: Aparna Chauhan, Mufiza Farid-Kapadia, Hersh Goel, Stephen J. Valerio, Neel Vaidya
Journal: Journal of Clinical Oncology (2025)

534 Background: In October 2022, the US FDA approved the STRIDE (Single Dose Tremelimumab Regular Interval Durvalumab) regimen, comprising tremelimumab 300 mg for 1 dose plus durvalumab 1500 mg every 4 weeks, for the 1L treatment of uHCC in adults aged ≥18 years. Thus far there is limited data characterizing STRIDE's 1L use in the real world. This observational study aims to describe patient characteristics, and clinical profiles of a 1L STRIDE cohort. Methods: A retrospective cohort study was conducted using EMR data from two community oncology practice networks, Florida Cancer Specialists and American Oncology Network, from January 1, 2018, to March 31, 2024. Adults with HCC who received ≥1 administration of the STRIDE regimen as 1L treatment following diagnosis were included. Patients with evidence of other cancers or systemic therapies pre-index date were excluded, to establish a cancer-naïve cohort at index. Index date was first administration of STRIDE. The analysis described the patient characteristics and clinical profile at index date. Patient demographics, severity indicators (cancer stage, albumin-bilirubin index (ALBI), alpha fetoprotein (AFP), Eastern Cooperative Oncology Group (ECOG)) and lab data were assessed on or closest to index date. Results: 79 patients initiated the 1L STRIDE regimen. The median (P25, P75) age at index was 70 (63.2-76.4) years. 72.2% were males, 64.6% were white, and 69.6% were overweight or obese patients. 95% had their first HCC diagnosis between 2022-2024 and the mean time from diagnosis to index date was 3.8 months (SD: 10.2). Among patients with reported cancer stage (n=57), most (82.5%, n=47) were diagnosed with stages IIIA to IVB. 18% had ECOG scores ≥2. 86% had ALBI grades between 2-3; 42.1% had AFP level ≥400 ng/ml; 30.4% had cirrhosis (among those that reported comorbidities) and 24.1% received any loco-regional therapy. Conclusions: Our study provides a real-world profile of patients on 1L STRIDE. Compared to the HIMALAYA trial, these findings suggest that patients in this real-world study tend to be older, diagnosed at late-stage, have a poor liver profile, and potentially worse prognosis over time. Further research is required to explore treatment pathways after index date, over a long follow-up, which may provide more insight into the continuity and effectiveness of IL STRIDE in the real-world.
Encorafenib and cetuximab with/without binimetinib therapies for patients with <i>BRAF</i> -mutated metastatic colorectal cancer with prognostic factors: The BEETS trial (JACCRO CC-18).
Authors: Yu Sunakawa, Eisuke Inoue, Daisuke Kotani, Tadamichi Denda, Chiaki Inagaki, Tomomi Kashiwada, Yosuke Horita, Akinori Sugaya, Yusuke Suwa, Takashi Ohta, Hidekazu Kuramochi, Kotoe Oshima, Manabu Shiozawa, Satoshi Yuki, Akihito Tsuji, Kei Muro, Wataru Ichikawa, Masashi Fujii
Journal: Journal of Clinical Oncology (2025)

164 Background: BRAF inhibitor combination therapies, triplet (encorafenib, binimetinib and cetuximab) and doublet (encorafenib and cetuximab), have been approved for BRAF -mutated metastatic colorectal cancer (mCRC) in Japan. The treatment with triplet is recommended for patients (pts) with clinical prognostic factors according to the sub-group analysis of the BEACON CRC trial. However, it is unclear whether the treatment strategy is useful. We therefore conducted a study on the use of combination therapy with triplet or doublet based on observational study that accumulated real world data. Methods: The BEETS trial was a multicenter observational study to prospectively evaluate the efficacy and safety of BRAF inhibitor combination therapy as a 2nd- or 3rd-line treatment in pts with BRAF -mutated mCRC in clinical practice [UMIN000045530]. Two hundred pts were assigned to either triplet or doublet therapy based on the physician’s choice. The primary endpoint was overall survival (OS). The secondary endpoints included overall response rate (ORR), disease control rate, progression-free survival (PFS), and safety. The exploratory analysis was performed to evaluate the efficacy of triplet and doublet therapies in all pts and pts with clinical prognostic factors (PS1, 3 or more metastatic sites, elevated CRP value, or primary tumor present) using inverse probability weighting (IPW) analysis based on propensity scores to account for potential cofounding factors. Results: Among 203 pts enrolled from Oct 2021 to Nov 2023, 195 pts were evaluable (median age 67 years old, 52% male, ECOG PS 0/1/2 55%/39%/6%, no. of prior regimens 1/2 85%/15%, right-sided primary 61%, MSI-high 7%, triplet regimen 57%). Median OS was 13.2 months (95%CI 11.4-17.4) with 1y-survival rate of 53%, and median PFS was 4.9 months. Comparing the triplet and doublet using IPW, the median OS and PFS were comparable between the two treatments (triplet vs. doublet; 16.0 months vs. 13.6 months [HR 0.88, 95%CI 0.53-1.48] and 5.7 months vs. 4.8 months [HR 0.87, 95%CI 0.59-1.28]). In 139 pts with any prognostic factors, median OS and 1y-survival rate were 13.2 months vs. 9.6 months [HR 0.80, 95%CI 0.45-1.43] and 54% vs. 42%, median PFS and ORR were 5.3 months vs. 4.2 months [HR 0.75, 95%CI 0.48-1.19] and 34% vs. 42%, in the triplet vs. doublet therapy, respectively. Conclusions: Our study demonstrated that BRAF inhibitor doublet therapy is a reasonable treatment for BRAF -mutated mCRC. However, triplet therapy may be a clinically useful for pts with clinical prognostic factors. Clinical trial information: UMIN000045530 .
A phase II, randomized study of JMT101 in combination with irinotecan and SG001 versus regorafenib in patients with metastatic colorectal adenocarcinoma (mCRC).
Authors: Jianmin Xu, Wentao Tang, Xiugao Yang, Yang Yang, Qiwen Chen, Jianhong Cheng, Xuechao Wan, Yane Song, Mengke Li
Journal: Journal of Clinical Oncology (2025)

TPS314 Background: Epidermal growth factor receptor (EGFR) inhibitorcombined withchemotherapy based on5-FU with oxaliplatin and irinotecanis the first-line treatment of wild-type RAS mCRC.JMT101 is a humanized monoclonal IgG1 antibody targeting EGFR. Previous trials showed that JMT101 monotherapy or in combination with chemotherapy had demonstrated a promising anti-tumor activity in advanced solid tumors with good safety profiles. EGFR inhibitor might have a synergetic effect with immunocheckpoint inhibitor (ICI) by activating innate and adaptive immune response. SG001 is a fully humanized and high-affinity immunoglobulin G4 monoclonal antibody that targets programmed death-1 (PD-1), which also had encouraging efficacy in advanced solid tumors. Therefore, EGFR antibody in combination with chemotherapy plus ICI is worthy exploration in patients with mCRC. Methods: This is a phase II, multicenter, open-label, two-part study. Part I is a safety run-in, followed by part II randomized treatment. Eligible patients are histologically confirmed mCRC without MSI-H/dMMR, wild-type RAS and BRAF, who progressed on at least 2 prior systemic therapy with chemotherapy based on 5-FU with oxaliplatin and irinotecan, with or without cetuximab and bevacizumab (both parts); no prior treatment with regorafenib, fruquintinib, or TAS-102 (part II). Safety run-in data will be analyzed after 3-6 patients have received JMT101 6 mg/kg plus irinotecan 180 mg/m 2 plus SG001 240 mg Q2W. Upon dose confirmation, 90 patients with mCRC will be randomized into three arms (1:1:1) to receive JMT101 plus irinotecan plus SG001, or JMT101 plus irinotecan, or regorafenib monotherapy. Primary endpoints include incidence of dose limiting toxicities (DLT) and adverse events (part I) and objective response rate (ORR) as per RECIST v1.1 by investigator (part II). Secondary endpoints include JMT101 and SG001 pharmacokinetic profile, antidrug antibodies (ADA) (both parts), disease control rate (DCR), duration of response (DOR), progression free survival (PFS), and overall survival (OS), as well as safety (part II). Prespecified goal for safety run-in part was met; randomized treatment part accrual began in February 2024. Clinical trial information: NCT06089330 .