tbuckley/cabot-search huggingface dataset:
The overall safety and short-term efficacy of nivolumab plus ipilimumab for advanced esophageal squamous cell carcinoma.
Authors: Kazuhiro Shiraishi, Shun Yamamoto, Yuri Yoshinami, Akihiro Ohara, Mai Itoyama, Kazuki Yokoyama, Yoshitaka Honma, Tairo Kashiraha, Daisuke Kurita, Koshiro Ishiyama, Junya Oguma, Hiroshi Igaki, Hiroyuki Daiko, Ken Kato
Journal: Journal of Clinical Oncology (2024)

329 Background: Although nivolumab plus ipilimumab (Nivo+Ipi) is strongly recommended as 1st-line treatment for patients with advanced esophageal squamous cell carcinoma (ESCC), tumor proportion score (TPS) should be considered. Despite the efficacy, patients who received Nivo+Ipi often experienced serious immune related adverse events (irAEs). However, there are few data on safety and short-term efficacy of Nivo+Ipi in real world. Methods: We retrospectively collected data of pts who received Nivo+Ipi for advanced ESCC between May 2022 to July 2023 in the National Cancer Center Hospital. We evaluated adverse events by CTCAE v5.0 and multivariate analysis using a logistic regression model. estimated overall response rate (ORR) by RECIST v1.1 and progression-free survival (PFS). Results: Thirty pts were subjects in this study. The characteristics were as follows: median age (range): 63.5 (36-80) years, male/female: 24/6, metastatic/recurrent: 3/27, ECOG PS 0/1≤: 16/14, PD-L1 TPS 1%≤: 17, number of organs with metastases 1/2≤: 13/17, treatment-line 1st/2nd≤ 6/24 Median follow-up time was 5.0 months (mo) (reverse Kaplan-Meier, 95%CI; 3.0-8.3 mo). Any grade and grade 3≤ irAEs were observed in 12 (40.0%) and in 5 pts (17.9%), respectively. In grade 3≤ irAEs, AST/ALT elevation (n=2, 7.1%), adrenal insufficiency (n=1, 3.6%), pneumonitis (n=1, 3.6%), myositis (n=1, 3.6%), encephalopathy (n=1, 3.6%), stevens-Johnson syndrome (n=1, 3.6%) were reported. The pts who received systemic steroid therapy was 8 pts (28.6%). Two pts received high-dose steroid with methyl-prednisolone, 1 g/body for 3 days, four pts needed steroid therapy with prednisolone, 1-2 mg/kg and two pts added mycophenolate mofetil. No treatment-related deaths were reported. For the pts who received Nivo+Ipi as a first-line treatment (n=6), 3 pts (50%) achieved partial response and 2 pts (33.3%) had stable disease. 6-mo PFS rate of the 1st line pts was 63%. For the pts who received Nivo+Ipi in later-line, the ORR and the median PFS were 33.3% and 2.6 mo (95%CI; 1.4-3.9 mo), respectively. Fifteen pts received subsequent systemic therapy, which consisted of taxane (12 pts), fluoropyrimidine plus platinum (2 pts) and 1 pt continued Nivo+Ipi beyond progression. Conclusions: Our study may demonstrate a consistent incident of irAEs in pts who received Nivo+Ipi in the real world, compared to the results of the CheckMate 648. Despite of the short time of follow-up period, 1st-line treatment with Nivo+Ipi appeared to be more efficacious than Nivo+Ipi used as a later-line treatment.
Predicting rapid progression and overall survival in stage II-III pancreatic cancer using a CT-based radiomic signature.
Authors: Qinmei Xu, Diego Augusto Santos Toesca, Emil Schueler, Arash Jamalian, Emel Alkim, Daniel Tandel Chang, George A. Fisher, Lucas Vitzthum, Olivier Gevaert, Haruka Itakura
Journal: Journal of Clinical Oncology (2024)

706 Background: We sought to assess the ability of a computed tomography (CT)-derived radiomic signature (RS) feature set to predict rapid tumor progression and overall survival (OS) in patients diagnosed with stage II-III pancreatic cancer undergoing stereotactic body radiation therapy (SBRT) in sequence with chemotherapy. Methods: We conducted a retrospective study on a cohort of 240 stage II-III pancreatic cancer patients who underwent SBRT in sequence with chemotherapy at a single institution (Stanford Hospital and Clinics). Among them, 83 had pre-SBRT contrast-enhanced CT images with segmented tumors, forming the imaging set, from which we extracted 900 radiomic (quantitative pixel-level imaging characteristic) features from delineated tumor regions-of-interest. For RS development, we divided the imaging set into a training set (n = 53) for model development and a test set (n = 30) for evaluation. We built a binary prediction model on the training set to identify patients at risk of rapid tumor progression within three months after SBRT. We utilized logistic regression with the Least Absolute Shrinkage and Selection Operator algorithm for feature selection and classification. To fine-tune parameters, we performed five-fold cross-validation on the training set, repeating each set of parameters five times. Finally, we assessed the model's performance on the test set (n = 30) using the area under the curve (AUC) value. We selected the model with the best AUC, while also generating the predictive radiomic feature set. For OS prognostication, we conducted both univariate and multivariate Cox proportional-hazards analyses using RS and clinical features (age, sex, stage, vessel involvement, tumor location, performance status, body mass index, biological equivalent dose of radiation) as potential predictors. Results: The enrolled cohort consisted of 127 men (mean age, 69 years ± 12 [SD]) and 113 women (mean age, 69 years ± 13 [SD]). Seventeen textural radiomic features were identified as the RS, which demonstrated a high AUC in the test set for the prediction of rapid progression (AUC 0.850; 95% CI: 0.725, 0.975). Age was associated with OS in the multivariate model while high RS (&gt;0.5) was independently associated with OS in both univariate and multivariate models. Conclusions: CT-derived RS, combined with age, represent the most prognostic factors for stage II-III pancreatic cancer. RS, which likely reflects underlying biology or molecular alterations, contributes to the highest HR of poor OS and provide the strongest indicator of outcome following commonly used treatments in this patient population. [Table: see text]
Development of an improved risk stratification scheme for stage II and III colorectal cancers through incorporation of the digital pathology biomarker QuantCRC.
Authors: Rish Pai, Christina Wu, Heidi E. Kosiorek, Imon Banerjee, Catherine E. Hagen, Christopher P. Hartley, Rondell P. Graham, Bassam Bassam Sonbol, Tanios S. Bekaii-Saab, Hao Xie, Frank A. Sinicrope, Bhavik Patel, Thomas Westerling-Bui, Sameer Shivji, James Conner, Carol Jane Swallow, Paul Savage, David Patrick Cyr, Richard Kirsch, Reetesh Pai
Journal: Journal of Clinical Oncology (2024)

162 Background: There is a need to improve current risk stratification of stage II and III colorectal cancer (CRC) to better inform risk of recurrence and guide adjuvant chemotherapy. The purpose of this study is to examine whether integration of QuantCRC, an AI-based digital pathology biomarker utilizing hematoxylin and eosin-stained slides, provides improved risk stratification over current American Society of Clinical Oncology (ASCO) guidelines. Methods: ASCO and QuantCRC-integrated risk schemes were applied to an observational cohort of 1,068 stage II and III CRCs. The stage II integrated scheme utilizes pT3 vs. pT4 and QuantCRC-derived risk groups. The stage III integrated scheme utilizes pT1-3 vs. pT4, pN1 vs. pN2, and QuantCRC-derived risk groups. Performance metrics included log-rank test, hazard ratios and Somers’ Dxy rank correlation. Results: Integration of QuantCRC provides improved risk stratification compared to the ASCO scheme for stage II and III CRC. The QuantCRC-integrated scheme placed more stage II tumors in the low-risk group compared to the ASCO scheme (69.3% vs. 60.4%) without decreased 3-year RFS. The QuantCRC-integrated scheme provided larger hazard ratios (HR) for both intermediate-risk (3.04, 95%CI 1.81-5.10, P=2.8x10 -5 ) and high-risk (4.62, 95%CI 2.02-10.61, P=0.0003) groups compared to ASCO intermediate-risk (2.09, 95%CI 1.21-3.63, P=0.008) and high-risk (3.08, 95%CI 1.57-6.01, P=0.001) groups. The QuantCRC-integrated scheme for stage III tumors identified a small group of 80/518 (15.4%) CRCs at very high risk of recurrence with HR of 4.08 (95%CI 2.68-6.23, P=6.5x10 -11 ) compared to a HR of 2.42 (95%CI 1.72-3.38, P=3.1x10 -7 ) for 228/518 (44.0%) high-risk CRCs in the ASCO scheme. QuantCRC-integrated risk groups remained prognostic in stage III CRCs when stratified by presence or absence of any adjuvant chemotherapy. No difference in RFS were seen in QuantCRC-integrated low-risk and intermediate-risk stage III CRCs stratified by 3 vs. 6-months of oxaliplatin-based adjuvant chemotherapy suggesting that these two groups can be treated with 3-months of adjuvant therapy. Conclusions: Incorporation of QuantCRC into risk stratification provides a powerful predictor of RFS that has potential to guide subsequent treatment and surveillance.
Neoadjuvant anti-programmed death 1 (PD-1) therapy in patients (pts) with resectable mismatch repair–deficient (dMMR) locally advanced rectal cancer (LARC): EPOC2201.
Authors: Hideaki Bando, Yuichiro Tsukada, Akinobu Taketomi, Satoshi Yuki, Yoshito Komatsu, Takashi Akiyoshi, Eiji Shinozaki, Yukihide Kanemitsu, Atsuo Takashima, Manabu Shiozawa, Akio Shiomi, Kentaro Yamazaki, Nobuhisa Matsuhashi, Hiroko Hasegawa, Takeshi Kato, Eiji Oki, Masashi Wakabayashi, Nozomu Fuse, Masaaki Ito, Takayuki Yoshino
Journal: Journal of Clinical Oncology (2024)

TPS226 Background: Neoadjuvant radiotherapy and chemotherapy followed by surgical resection is a standard treatment for LARC. As anti-PD-1 therapy for patients with dMMR colorectal cancer is responsive in the context of metastatic disease, several clinical trials which evaluate the efficacies of anti-PD-1 therapy in patients with dMMR LARC are on-going and suggested the outstanding responses (Cercek A. et al., N Engl J Med 2022). Methods: We initiated the EPOC 2201 VOLTAGE-2 study, which is an ongoing, non-randomized, single-arm phase II trial. The major eligibility criteria were as follows: treatment-naïve with rectal cancer located 12 cm from the anal verge; confirmed dMMR; clinical stage II/III in primary cohort (N=35) and stage I in exploratory cohort (N=20); age ≥ 18; Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1; and presence of sufficient organ function. The study treatments include 12 cycles of nivolumab (NIVO) monotherapy (240 mg every 2 weeks) followed by assessment using Memorial Sloan Kettering (MSKCC) Regression Schema (Smith J.J. et al., BMC Cancer 2015). If clinical complete response (cCR) or near complete response (nCR) are observed, non-operative management with additional 12 cycles of NIVO will be performed. If incomplete response (IR) is observed, standard chemoradiotherapy with 50.4Gy of radiation plus capecitabine followed by surgery will be performed. The primary endpoint is the 2-year cCR rate in primary cohort. Various survival endpoints including progression-free survival (PFS) and overall survival (OS) are assessed as secondary endpoints. Safety analyses are performed using the Common Terminology Criteria for Adverse Events (CTCAE) ver. 5.0, and the Clavien‒Dindo classification (ver. 2.0) is added for postoperative complications. Assuming null and alternative hypotheses, cCR rates of 23% and 45%, the planned sample size for primary cohort was set at 35, with a one-sided alpha of 5% and power of 80%. An exploratory biomarker study was also conducted using serially collected tumor and blood samples. Whole genome-based minimal residual disease (MRD) assay and whole exome/whole transcriptome-based tumor and immune microenvironment analyses are performed. As of August 2023, patient’s enrollment is ongoing. Clinical trial information: jRCT2031220484 .
Real-world (RW) characteristics, treatment patterns, and outcomes of patients with cholangiocarcinoma (CCA) treated with pemigatinib.
Authors: Kim Saverno, Cherrishe Brown-Bickerstaff, Angele Kotomale, Michael A. Rodriguez, Bruce A. Feinberg, Sarah Gordon, Haobo Ren, Evan Mark Braunstein, Richard D. Kim
Journal: Journal of Clinical Oncology (2024)

444 Background: Pemigatinib demonstrated efficacy in fibroblast growth factor receptor (FGFR)–altered CCA in the FIGHT-202 trial; however, limited RW evidence exists on treatment patterns and outcomes in patients (pts) with CCA treated with pemigatinib. This study assessed characteristics, FGFR2 testing patterns, treatment patterns, and outcomes of pts treated with pemigatinib for locally advanced or metastatic CCA in the United States as part of routine clinical care. Methods: This retrospective, multisite cohort study included pts with a diagnosis of unresectable locally advanced or metastatic CCA who were initially prescribed pemigatinib on or after 04/17/2020. Eligible pts were ≥18 years at pemigatinib prescription and had ≥4 months (mo) of follow-up (unless &lt;4 mo due to death). Pts who received pemigatinib as part of a clinical trial or those who received systemic therapy for another primary malignancy (other than cancer of unknown primary or hepatic cancer) were ineligible. Participating physicians from Cardinal Health’s Oncology Provider Extended Network—approximately 72% from community oncology practices—abstracted data from the medical records of eligible patients into electronic case report forms. Results were summarized using descriptive statistics. Results: Data from 120 pts (49% male; 55% White; 19% Hispanic; median age at pemigatinib prescription, 65 years) were collected from 18 physicians/practices. Testing for FGFR2 alterations was completed in 93% (n=111) of pts; of those, all but one patient (result unknown) tested positive, and 95% were tested using next-generation sequencing. At time of pemi prescription, 90% of pts had metastatic disease. Across all pts, 94% and 6% were prescribed pemigatinib as 2nd and 3rd line of therapy, respectively. The most common starting dosage was 13.5 mg daily for 14 days of 21-day cycle (87.5% of pts). Among the 60 pts who discontinued pemi during the 6.5-month median study follow-up period, 68% discontinued due to disease progression. Median RW progression-free survival (rwPFS) from date of pemigatinib initiation was 7.4 (95% CI: 6.4–8.6) mo. Among the 116 patients with tumor response data available, RW overall response rate (rwORR) was 61% (95% CI: 52% - 71%). Conclusions: This study complements the FIGHT-202 clinical trial by assessing the use of pemigatinib among a diverse population of patients with CCA under RW conditions. Secondarily, the rwORR and rwPFS from this study support the clinical benefit of pemigatinib demonstrated in FIGHT-202.
A phase Ib/II study of ASKB589 (anti-Claudin 18.2 [CLDN18.2] monoclonal antibody) combined with CAPOX and PD-1 inhibitor as first-line treatment for locally advanced, relapsed and metastatic gastric/gastro-esophageal junction (G/GEJ) adenocarcinoma.
Authors: Zhi Peng, Lin Shen, Ying He, Jing Chen, Barbara Hickingbottom, Jianfeng Lu
Journal: Journal of Clinical Oncology (2024)

317 Background: ASKB589 is a humanized IgG1 monoclonal antibody against Claudin 18.2 (CLDN18.2) with high affinity and enhanced antibody-dependent cytotoxicity. We report preliminary safety and efficacy data from an ongoing Phase Ib/II, dose-escalation and expansion study of ASKB589 combined with capecitabine, oxaliplatin(CAPOX) and Sintilimab as first-line treatment of G/GEJ adenocarcinoma (NCT05632939). Methods: The study enrolled G/GEJ adenocarcinoma patients(pts) with CLDN18.2 positive expression. The dose-escalation phase used a 3 + 3 design to determine the maximum tolerated dose (MTD). In expansion, the dose of ASKB589 selected for expansion was based on the safety, tolerability, pharmacokinetics and antitumor activity during escalation phase. Responses were assessed by RECIST 1.1 every 2 cycles (6 weeks). Adverse events (AEs) were graded using CTCAE v5.0. In escalation, pts received ASKB589 intravenously (IV) at doses of 6 mg/kg (n = 3) and 10 mg/kg (n = 6) every 3 weeks (Q3W) combined with CAPOX and Sintilimab. In expansion, all pts received ASKB589 IV at a dose of 6 mg/kg. Results: As of July 20, 2023, 9 pts were enrolled in escalation. No DLT was observed and thus the MTD was not identified. 9(100%)pts had treatment-related adverse events (TRAEs), the most common being nausea (77.8%), hypoproteinemia (66.7%), and hyponatremia (55.6%). While the majority of TRAEs were grade 1 or 2, 1 pt (11.1%) had a grade 3 TRAE (decreased neutrophils [10mg/kg]). In expansion, 26 pts with CLDN18.2 moderate-to-high expression (≥2+ membrane staining intensity in ≥40% of tumor cells) were included in the safety set. 24(92.3%) pts had TRAEs, the most common being nausea (65.4%), vomiting (53.8%), hypoproteinemia (53.8%), anemia (50.0%), fatigue (26.9%) and decreased neutrophils (23.1%). 3 pts (11.5%) had TRAEs of grade ≥3 including hypocalcemia, hypokalemia, decreased neutrophils, fatigue and bone marrow suppression. For the 15 evaluable pts who had at least one post-baseline tumor assessment, 12 pts (80.0%) achieved PR for an unconfirmed objective response rate (ORR) of 80.0%. 3 pts (20.0%) had SD for a disease control rate (DCR) of 100.0%. The PK of ASKB589 at doses of 6mg/kg and 10mg/kg combined with CAPOX and anti-PD1 therapy was consistent with that of monotherapy. Conclusions: ASKB589 combined with CAPOX and PD-1 inhibitor has manageable safety and promising antitumor activity. 6mg/kg is chosen as the recommended dose in subsequent studies. Clinical trial information: NCT05632939 .
Real-world clinical characteristics and treatment patterns among people with hepatocellular carcinoma in the United States (US) treated with resection or ablation.
Authors: Neehar Parikh, Dex L. Underwood, Jenny Hu, Heide A. Stirnadel-Farrant, Nehemiah Kebede, Ravi Patel, Kirema Garcia-Reyes
Journal: Journal of Clinical Oncology (2024)

436 Background: Treatment guidelines for early-stage hepatocellular carcinoma (eHCC) include therapies with curative intent comprising three primary strategies: liver transplantation, surgical resection, or ablation (for small lesions). However, many people experience HCC recurrence, with recurrence rates of up to approximately 80% within 5 years after resection. Furthermore, contemporary insights into the eHCC treatment landscape and post-recurrence treatment patterns in the real-world setting are lacking. This study was designed to assess demographic and clinical characteristics and treatment patterns for people with HCC who received resection or ablation as a proxy for defining early-stage disease. Methods: This was a retrospective observational cohort study of adults with HCC treated with resection or ablation in the US, conducted using linked electronic health records and healthcare claims from Optum’s de-identified Market Clarity Data. Index date was the date of the first observed resection or ablation between July 2016 and March 2021. Baseline characteristics were assessed in the 6-month period prior to index, and patients (pts) were followed until end of continuous enrolment in a medical and pharmacy plan, death, or data cut-off (September 2022), whichever occurred first. Demographic and clinical characteristics and treatment patterns, including subsequent treatments, were described. Results: A total of 649 pts met the study criteria and were included in the analyses. The median duration of follow-up was 23.0 months (range: 0.03–74.55 months). The mean age at index was 64.1 years (median 64.0 years), with a majority male gender (72.9%) and White race (65.5%). A total of 385 pts (59.3%) underwent ablation only, 242 pts (37.3%) underwent resection only, and 22 pts (3.4%) underwent both procedures at index. Transarterial embolization alone was received by 57 (8.8%) pts and was the most common embolization procedure received during follow-up, followed by transarterial chemoembolization alone in 46 (7.1%) pts and transarterial radioembolization in 46 (7.1%) pts. A total of 88 (13.6%) pts received systemic therapies for HCC (tyrosine kinase inhibitors, programmed cell death protein-1/programmed cell death-ligand 1/cytotoxic T-lymphocyte-associated antigen 4 inhibitors, or angiogenesis inhibitors) during follow-up. Conclusions: In this real-world cohort, ablation was the most received curative intent therapy for HCC. Among treatments received during follow-up, locoregional therapies were used most often, followed by systemic therapies. Although limited by its retrospective, observational nature, short duration of follow-up, and availability of data in the database, the results of this analysis provide a contemporary landscape of early-stage treatments for HCC in the real-world setting.
Phase Ib trial of durvalumab plus tremelimumab in combination with particle therapy in advanced hepatocellular carcinoma patients with macrovascular invasion: DEPARTURE trial.
Authors: Sadahisa Ogasawara, Keisuke Koroki, Hirokazu Makishima, Masaru Wakatsuki, Asahi Takahashi, Hiroaki Kanzaki, Kazufumi Kobayashi, Masanori Inoue, Soichiro Kiyono, Masato Nakamura, Naoya Kanogawa, Takayuki Kondo, Shingo Nakamoto, Yuki Shiko, Yoshihito Ozawa, Yosuke Inaba, Tomoya Kurokawa, Hideki Hanaoka, Shigeru Yamada, Naoya Kato
Journal: Journal of Clinical Oncology (2024)

480 Background: The HIMALAYA study established the efficacy and safety of durvalumab combined with tremelimumab (STRIDE) as a first-line treatment for advanced hepatocellular carcinoma (HCC). Carbon ion radiotherapy (C-ion RT), a type of particle therapy, allows precise tumor targeting while sparing nearby normal tissue. In HCC, macrovascular invasion (MVI) signifies aggressive progression with poor outcomes. Our strategy used C-ion RT to target a key tumor with MVI for disease management and potential MVI control, complemented by STRIDE. Recognizing that radiation therapies, including C-ion RT, stimulate immune responses, notably releasing tumor antigens and DAMPs (immune priming), we posited that merging C-ion RT with STRIDE might enhance therapeutic effects. Methods: This is a Phase Ib, multicenter study evaluating durvalumab with particle beam radiotherapy in HCC patients with MVI (Cohort A) and STRIDE (Cohort B). Both cohorts began with patients resistant to standard treatments. After safety confirmation, the study expanded to include systemic therapy-naïve patients, totaling 15. C-ion RT begins after day 8 of the first cycle, following the initial drug dose. The relative biological effectiveness weighted dose is set at 60 Gy in four fractions over one week, targeting one representative intrahepatic nodule with MVI. The primary endpoint is adverse event rates, including dose limiting toxicity (DLT), with secondary endpoints on progression free survival (PFS) and overall survival (OS) (jRCT2031210046). Results: From July 2021 to January 2023, 15 advanced HCC patients were enrolled in our study (Cohort A: 3, Cohort B: 12). Four in Cohort B were systemic therapy-naïve. All cases confirmed MVI radiologically; with tumor invasion observed in the main portal vein for 4 patients and in the inferior vena cava for one. DLT evaluations in 3 from each cohort showed no incidents. While Cohort A had no adverse events, 4 patients in Cohort B (26.7%) experienced serious treatment-related adverse events. Cohort B's median PFS was a significant 2.79 months (95%CI, 1.12–6.64). The 6- and 12-month PFS rates stood at 38.1% and 12.7% respectively. The median OS is still undetermined, but promisingly, the 6- and 12-month survival rates both reached 87.5%. Conclusions: The safety of STRIDE in combination with particle therapy has been confirmed in advanced HCC with MVI. This combination, especially the irradiation of tumors with MVI using C-ion RT, holds promise in managing prognostic determinant tumors and potentially enhancing OS. Clinical trial information: jRCT2031210046 .