tbuckley/cabot-search huggingface dataset:
QL1203 vs placebo plus mFOLFOX6 as first-line therapy in RAS wild-type, metastatic colorectal cancer (mCRC): Interim analysis (IA) of a multicenter, randomized, double-blinded, parallel, phase 3 trial.
Authors: Weijian Guo, Yusheng Wang, Wenhui Yang, Yunfeng Li, Yanqiao Zhang, Zhongtao Zhang, Hailin Xiong, Changzheng Li, Zhiwu Wang, Nanfeng Fan, Xianli Yin, Peng Du, Suxia Luo, Jingdong Zhang, Dajun Yu, Weie Zheng, Xiaoyan Kang, Kaisheng Mao, Zhan Wang, Lin Shen
Journal: Journal of Clinical Oncology (2025)

190 Background: Panitumumab plus FOLFOX or FOLFIRI has been approved as the first-line therapy for RAS wild-type mCRC. QL1203 is a panitumumab biosimilar showing similarity to the originator panitumumab (Vectibix, Amgen) in preclinical studies and phase 1 clinical pharmacokinetic study. Here we present results from interim analysis of a phase 3 trial (NCT04233151) investigating QL1203 vs placebo plus mFOLFOX6 as first-line therapy in Chinese patients (pts) with RAS wild-type mCRC. Methods: Pts with treatment-naïve, RAS and BRAF wild-type, mCRC unsuitable for radical resection and local therapy were enrolled and randomly assigned (2:1) to receive QL1203 (6 mg/kg) plus mFOLFOX6 once every 2 weeks (Q2W) or placebo plus mFOLFOX6 Q2W, stratified by primary tumor site, liver metastases, and previous neoadjuvant/adjuvant therapy. The primary endpoint was PFS assessed by a Blinded Independ Review Committee (BICR) per RECIST v1.1. Key secondary endpoints include PFS by investigator (INV), OS, ORR, DoR, and safety. This planned IA was conducted at 338 (81.25%) of 416 PFS events occurred. Results: From Jan 8, 2020 to Jun 12, 2023, 641 pts were randomized (QL1203/placebo, n=426/215). 551 (86.0%) pts had left-sided tumors (QL1203/placebo, 85.9%/86.0%). 433 (67.6%) pts had liver metastases (QL1203/placebo, 68.1%/66.5%). As of data cutoff of this IA (Mar 22, 2024), median follow-up was 23.8 months. Median PFS by BIRC was 11.20 months for QL1203 and 8.34 months for placebo (hazard ratio [HR], 0.61 [97.42% confidence interval [CI], 0.47-0.79]; stratified one-sided log-rank p&lt;0.0001). Other efficacy results are presented (Table). Incidence of grade≥ 3 adverse events (AEs) related to study drug was 59.9% for QL1203 and 32.9% for placebo. The most common grade≥3 AE related to QL1203 was neutrophil count decreased (20.3%). Conclusions: QL1203 demonstrated significantly improved PFS versus placebo and higher ORR. Clinical trial information: NCT04233151 . QL1203 (n=426) Placebo (n=215) PFS by BIRC mPFS, months (95% CI) 11.20 (9.89-13.11) 8.34 (7.26-8.54) HR (97.42% CI) 0.61 (0.47-0.79) PFS by INV mPFS, months (95% CI) 10.91 (9.69-11.30) 8.41 (7.39-9.07) HR (95% CI) 0.74 (0.60-0.91) mOS, months (95% CI) 27.66 (24.74-32.79) 24.54 (20.17-27.79) HR (95% CI) 0.82 (0.64-1.06) ORR by BIRC, n (%) 68.31% 47.91% 95% CI 63.66-72.70 41.07-54.81 ORR by INV, n (%) 64.08% 49.30% 95% CI 59.33-68.65 42.44-56.19
TAS102 in combination with oxaliplatin (TASOX) for refractory metastatic colorectal cancer.
Authors: Sharon Li, Fan Ling, Christian Misdary, Hao Liu, Manda DiRubbo, Patrick M Boland, Lyudmyla Derby Berim, Pat Gulhati, Seth D. Cohen, Jessica Leland Taff, Ankit Shah, Patrick Lee, Delia Radovich, Stuart P. Leitner, Michael Scoppetuolo, Howard S. Hochster
Journal: Journal of Clinical Oncology (2025)

189 Background: TAS102 (trifluridine/tipiracil hydrochloride) is approved for use alone or with bevacizumab in late line metastatic colorectal cancer (mCRC), with overall survival benefit in phase 3 trials (RECOURSE and SUNLIGHT). Oxaliplatin is frequently reintroduced after progression, resolution of limiting neuropathy, or disease recurrence post adjuvant therapy. In preclinical studies, oxaliplatin combined with TAS102 has shown synergism. We hypothesized TASOX may be an option for patients who have progressed/recurred after FOLFOX. Methods: We assessed safety and efficacy of TAS102 with oxaliplatin, enrolling patients with metastatic CRC progressed on ≥2 lines of therapy including 5FU, oxaliplatin and irinotecan. Patients with recurrence during or within 6 months of adjuvant chemotherapy were allowed. Exclusion: Prior TAS102 exposure, functional impairing peripheral neuropathy, ≥Grade 3 hypersensitivity to oxaliplatin, or uncontrollable grade 1-2 hypersensitivity to oxaliplatin. Treatment continued until disease progression or unacceptable toxicity. Patients received oxaliplatin 85 mg/m2 and TAS-102 35 mg/m2 bid days 1-5 every two weeks, and bevacizumab per MD choice. The primary endpoint was overall response rate (ORR) by RECIST (by independent radiologists). Secondary endpoints included disease control rate (DCR), safety and tolerability. Results: 54 patients enrolled; 53 received treatment on study and 48 had ≥1 disease assessment (median age 59, 58 % male, tumor RAS mutated 69%). Median time on study was 4 months (8 cycles; range 1-37 cycles). ORR was 6% (n=3), with average change in target lesions -45% (range -35 to -67%). 71% (n=34) had SD defined on study, with average change in target lesions -3% (range -29% to +20%). In those treated with bevacizumab (59%; n=28 ), 79% (n=22) had disease control vs. 75% (n=15). The most common reason for study discontinuation was progressive disease (23%, n=11). 68% (n=36) had a treatment-related adverse event (TRAE) ≥Grade 3 at any point during therapy. The most common G3 TRAEs were anemia 19% (n=10) and leukopenia 28% (n=15) at any time. Two (4%) developed grade 3 neuropathy. Conclusions: TASOX is effective as a 3rd line therapy for patients with mCRC. In our study, overall disease control rate was 77% with up to 19 months on study. Anemia and leukopenia are common but manageable. Bevacizumab did not seem to have as great an effect in our trial as observed in SUNLIGHT. Future studies would warrant TASOX in combination to bevacizumab in randomized trials in candidates for oxaliplatin retreatment. Clinical trial information: NCT02848079 .
OP-TNT: Phase II study of total neoadjuvant chemoradiotherapy followed by local resection for early distal rectal carcinoma.
Authors: Zhang Xian, Yang Qian, Ye Wei, Li Ren, Lechi Ye, Yunshi Zhong, Wenju Chang, Qingyang Feng, Shengxiang Rao, Liheng Liu, Lihong Huang, Yuan Ji, Yichen Wang, Jianmin Xu, Jian Wang
Journal: Journal of Clinical Oncology (2025)

177 Background: Surgery is standard of care for pMMR early distal rectal cancer (RC), which can be partially exempted by totally neoadjuvant chemoradiotherapy (TNT) followed by watch and wait. But long-term data showed that 1/3 patients had local growth( mostly in the rectal wall)in two years. This study investigates the efficacy and safety of TNT followed by local excision( LE) for early distal rectal carcinoma (cT1-3N0M0) in order to preserve organs. Methods: In this single-arm, phase 2 prospective trial, patients were eligible if they were aged 18 years or older, with a performance status of 0-1,newly diagnosed, biopsy proven pMMR/MSS RC which located ≤5cm from the anal verge and staged as cT1-3N0M0. Patients were assigned to receive TNT: 6 courses of CapOx(capecitabine 1000 g/m2 PO BID D1-14, oxaliplatin 130 mg/m2 IV QD D1,Q3W), combined with concurrent long-course radiotherapy (LCRT)(45 Gy/25 Fx to the pelvis with an SIB of 50 Gy/25 Fx to the tumor bed). Evaluation was performed 12 weeks after completion of LCRT. Patients who achieved a clinical complete response (cCR) or near clinical complete response (ncCR)were assigned to LE, whereas those with &gt;ypT1, positive margin, or neurovascular invasion after LE were recommended for total mesorectal excision (TME). The primary endpoint is the 3-year organ-preserving rate. Secondary endpoints include the pathological complete response (pCR)(encompassing response after LE and TME), adverse effects rate, 3y-disease-free survival (DFS)and 3y-overall survival (OS)rate. Results: From October 2022 to August 2024, 52 patients had completed therapy. Median age at evaluation and follow-up duration were 58.3 years and 11 months. Of the patients 78.8% (41/52) were defined as MRI stage T3, and 76.9%(40/52) located ≤3cm from the anal verge. Of 52 evaluable patients ,82.7% (43/52) achieved cCR/ncCR and had LE (6 via endoscopic resection and 37 through trans-anal minimally invasive surgery). Among these patients, 25.6% (11/43) were found to have residual tumors after LE, of which 6 were radical-operated while 5 refused this intervention. Nine patients who did not achieve cCR or ncCR received TME resection, and 6 of them were confirmed as pCR. The total pCR rate was 73.1% (38/52). Of all patients, 3 underwent abdominoperineal resection, and sphincter-preserving rate was 94.2%(49/52). No grade 3 or 4 adverse events were reported, and there were no treatment-related deaths. The main adverse event after local resection was the 1-3 months anterior resection syndrome. Conclusions: The results of interim analysis showed that tumor residue was found in patients with cCR/ncCR after TNT, similar to the regrowth rate previously reported. LE strategy may become prevention. Long-term outcomes are being followed up. Clinical trial information: NCT05563922 .
Surufatinib combined with TAS-102 as a late-line therapy in patients with metastatic pancreatic cancer (mPDAC): Updated results of a single-arm, phase II trial.
Authors: Dong-Sheng Zhang, Yun-Xin Lu, Fu-Rong Liu, Bing Bai, Yang Zhang, Zhiqiang Wang, Yu Liu, Jian-Wen Chen, Yu-Hong Li, Feng-Hua Wang, Gui Fang Guo, Feng Wang, Rui-Hua Xu
Journal: Journal of Clinical Oncology (2025)

739 Background: Patients (pts) with mPDAC recurrent after FOLFIRINOX and AG chemotherapies have few treatment options. Previous reports of NCT05481463 showed promising clinical benefits of surufatinib (a small-molecule inhibitor of VEGFR1-3, FGFR1 and CSF-1R) plus TAS-102 (combination of trifluridine and tipiracil hydrochloride) in recurrent mPDAC pts. Here, we report the updated results. Methods: This is a single-arm, phase II trial (NCT05481463). Eligible pts with histologically confirmed mPDAC, who had progressed after ≥ 2 lines of previous therapies were treated with surufatinib (250mg, qd, po, q4w) and TAS-102 (35 mg/m 2 , bid, po, days 1–5 and 8–12, q4w). The primary endpoint was progression-free survival (PFS). Key secondary endpoint was overall survival (OS). Other secondary endpoints included objective response rate (ORR), disease control rate (DCR), and safety. Results: Up to Sep 18, 2024, 20 pts were enrolled (median age 58 years, male 70.0%, TNM stage IV 100.0%, ECOG PS 1 100.0%, liver metastasis 50.0%, peritoneum metastasis 50.0%). Median baseline CA19-9 level of the 20 pts was 996.7u/ml, with a range from 2u/ml to 16612u/ml. 40.0% of pts had received 3L prior therapies before enrollment and 70.0% with primary site on pancreatic body and tail. All pts had received at least one post-baseline tumor assessment (evaluable), among which ORR was 15.0% (3 PRs), DCR was 30.0% (3 PRs, 3SDs). 35.0% pts had stable or shrinking tumors. Median PFS was 2.35m (95% CI 1.91-3.94). Median OS was 6.44m (95% CI 3.81-NR). In subgroup analysis, significantly longer PFS&amp;OS were observed in pts without liver metastasis (mPFS: 3.42m vs 2.01m, p=0.049; mOS: 9.92m vs 3.70m, p=0.026), or with ≤ 2 metastatic organs (mPFS: 3.94m vs 1.91m, p=0.005; mOS: 10.09m vs 3.81m, p=0.003). Additionally, OS was significantly prolonged in pts with baseline CA19-9 level ≤ 996.7u/ml, in contrast with those with baseline CA19-9 level more than 996.7u/ml (9.92m vs 3.70m, p=0.008). All pts experienced treatment emergent adverse events (TEAEs). Most common (≥ 10%) TEAEs (any grade) were anemia (59.1%), neutropenia (54.6%), leukopenia (50.0%), and lymphopenia (45.5%). Grade ≥ 3 TEAEs included neutropenia (31.8%), lymphopenia (13.6%), and anemia (9.1%). Conclusions: Surufatinib plus TAS-102 showed encouraging survival benefits and promising anti-tumor activity with acceptable toxicity in the late-line treatment of refractory mPDAC, especially in patients without liver metastasis, with ≤ 2 metastatic organs, or with baseline CA19-9 level ≤ 996.7u/ml. The results warrant further investigations in a large cohort. Clinical trial information: NCT05481463 .
Survival analysis using neoadjuvant rectal score in patients with locally advanced rectal cancer who underwent surgery after neoadjuvant chemoradiotherapy: An ambispective study.
Authors: Mohammed Sameer, Akhil Thomas Jacob, Madhu Muralee
Journal: Journal of Clinical Oncology (2025)

172 Background: Colorectal cancer, the third most common malignancy and a major cause of cancer deaths, is treated using a standard protocol of neoadjuvant chemoradiotherapy (NACTRT) or short-course radiotherapy (SCRT) followed by total mesorectal excision (TME) for locally advanced rectal cancers (LARC). Long-term follow-up is essential to determine study endpoints, necessitating surrogate markers for short-term outcomes. This study aims to stratify patients into risk groups based on their Neoadjuvant Rectal Cancer (NAR) score and evaluate its predictive value for oncological outcomes, including overall survival, disease-free survival (DFS), locoregional relapse-free interval (LRFI), and distant metastasis-free interval (DMFI), while also correlating clinicopathological characteristics with these outcomes. Methods: This ambispective observational study at the Regional Cancer Centre, Thiruvananthapuram, involved 459 patients with biopsy-proven, locally advanced rectal adenocarcinoma (T3/T4 and/or node positive) who underwent long-course neoadjuvant chemoradiotherapy (NACTRT) followed by curative surgery (Anterior Resection or Abdomino-Perineal Resection) between 2010 and 2015, with a minimum follow-up of three years. Exclusion criteria included previous malignancies, synchronous colorectal cancers, oligometastatic disease, and loss to follow-up. The study aimed to determine the predictive value of the Neoadjuvant Rectal Cancer (NAR) score for oncological outcomes. Clinicopathological details were collected from case records, imaging, and operative notes, and postoperative histopathological records were used to calculate the NAR score. Patients were categorized into three groups based on their NAR scores and followed prospectively for recurrence or death. Data were analyzed using frequency, percentages, mean, standard deviation, Chi-square test, Kaplan-Meier method, log-rank test, and Cox regression analysis, with a significance level set at p &lt; 0.05. Results: 459 patients were included in the study, with 41.4% females, and 44% being less than 60 years. Most of the patients had lesion 5-10 cm from anal verge (46%). 77% of patients had T3 disease prior to the start of NATCTRT. 51.9% had underwent APR, and 80.4% had open surgery. 11.1% had PCR attained. 27% had disease recurrence of which most were distant metastasis. NAR was a significant predictor of overall survival, disease free survival, distant metastasis free interval and locoregional failure free interval. Other significant predictors of overall survival were pre-NACTRT T stage, pN stage, PLNR, CRM status and PCR, but only NAR was found to be significant on multivariate analysis. Conclusions: NAR score is a significant predictor of OS, DFS,LRFI and DMFI and can be used as a short term surrogate for survival data in anticipated trials.
Intra-Stent Thrombosis Secondary to the Allergic Reaction by Contrast in Elective Percutaneous Coronary Intervention, a Rare example of Kounis Syndrome, a Case Report
Authors: Muhammad Muneeb Arshad
Journal: Clinical Cardiology and Cardiovascular Interventions (2024)

Background: Kounis syndrome is the development of ACS secondary to allergic reaction. We are presenting case report of KS that developed due to allergic reaction in patient undergoing elective angiography and resulted in STEMI. Case Presentation 64year old female underwent elective PCI for angina refractory to anti-anginal therapy. CTCA demonstrated severe Diagonal 2 Coronary artery disease. Due to on-going angina she was listed for coronary angiogram +/- PCI. Iodixanol was used as contrast medium.This revealed severe disease in the D2. Initially drug coated balloon to D2 used. But DCB of D2 causes dissection. We decided to deploy 2.25x24mmDES overlapping with 2.5x14mmDES. Final results were satisfactory. In recovery urticarial rash noticed on her back. IV Hydrocortisone 100mg and IV Chlorphenamine 10mg was administered. Shortly after, she developed chest pain with ST elevation in lead 1 and aVL. She was immediately taken for PCI. Iohexol contrast was administered to the patient. There was acute stent thrombosis, which when re wired allowed flow to be restored and ECG changes to resolve. Patient developed severe hypotension. A widespread urticarial rash noted over the body with peri-orbital and facial swelling. Patient stabilised with iv adrenaline infusion and transferred to CCU. She was started on oral prednisolone. Patient developed pain in right Iliac fossae after removal of the femoral line next day. She developed abdominal distension and severe hypotension. Her CT AP showed large retroperitoneal hematoma with extravasation from external iliac artery. Via interventional radiology lower dose of Iohexol was used and a stent was inserted in EIA. Patient was moved to ICU. She was discharged home 4 days later with dual antiplatelet for 1 year followed by lifelong Aspirin. Discussion: This case was diagnosed with KS by Iodixanol as the source of anaphylaxis. There is need to treat KS as a separate entity in ACS guidelines.
The role of stereotactic radiotherapy in brain metastases from gastrointestinal cancer.
Authors: Michele Aquilano, Mauro Loi, Marianna Valzano, Giulio Frosini, Ilaria Morelli, Isacco Desideri, Daniela Greto, Pierluigi Bonomo, Alessandra Galardi, Pietro Garlatti, Luca Visani, Lorenzo Livi
Journal: Journal of Clinical Oncology (2025)

181 Background: The incidence of brain metastases from Gastrointestinal primary tumors (GI-BMs) is approximately of 6%. Appropriate management of these patients, who often presents at advanced disease stage, is poorly defined. Stereotactic Radiotherapy (SRT) could be proposed to improve symptoms and extend disease control. The aim of this study is to assess the impact of SRT in this population. Methods: Data from consecutive patients treated for GI-BMs with SRT from March 2015 to March 2024 were retrospectively collected. Dose was expressed as Equivalent Dose in 2Gy Fractions (EQD2). lntra-Cranial Control (IC) and Overall Survival (OS) were calculated from date of SRT to event (intracranial relapse and death respectively) or last follow-up. Results: Fifty-four patients (median age 68 years, range 46-84) accounting for 98 GI-BMs were included. Primary tumors were colorectal and gastro-oesophageal adenocarcinoma in 37 (68.5%) and 17 (31.5%) patients respectively. Eighteen (33%) patients presented with a single GI-BM. Extra-cranial disease was present in 41 (76%) patients, including unresected/relapsing primary tumor in 9 (17%) cases. Detection of BMs occurred at diagnosis in 8 (15%) patients, as first site of relapse in 27 (50%) or as progression of known metastatic disease in 19 (35%) patients. Before SRT, surgery and/or WBRT were performed in 10 (19%) and 5 (9%) patients respectively. For each SRT course a median of 1 (range 1-5) GI-BMs was treated. Dose regimens consisted of 12-30 Gy in 1-5 fractions, to a median EQD2 of 50 Gy 10 (range 22-68). A second SRT course for out-of-field intracranial progression was performed in 7 patients (13%). First- and further chemotherapy lines were administered in 39 (72%) and 15 (28%) patients respectively. IC rate was 88% at 6 months and 70% at 1 year. At univariate analysis (UVA) no variables were correlated with IC. Median OS was 11 months (IC 95% 9-16), 6-months and 1-year OS rate was respectively 76% and 48%. Only systemic treatment beyond first line was correlated with OS at UVA (4 versus 15 months, p=0.02). Two (4%) patients developed mild symptomatic radionecrosis. Conclusions: Onset of GI-BMs can occur at any stage of disease. Despite poor overall outcome, selected patients may benefit from SRT to improve IC, particularly in association with first-line systemic treatment. Multiple SRT courses can be delivered in case of further intracranial recurrence. Symptomatic radionecrosis may occur in less than 5% of cases.
A phase Ib study of immunotherapy with ex-vivo pre-activated and expanded CBNK cells in combination with cetuximab, in patients with colorectal cancer (CRC) with minimal residual disease (MRD): Final report.
Authors: Maria Pia Morelli, Rafet Basar, David Marin, Ryan W Huey, Pinaki Prosad Banerjee, Jason Willis, Van K. Morris, Hind Rafei, Arvind Dasari, Bryan K. Kee, Brittany E Zeller, Stacy Diao, David Menter, Elizabeth J. Shpall, Scott Kopetz, Katy Rezvani
Journal: Journal of Clinical Oncology (2025)

176 Background: Colorectal cancer (CRC) is the second most common type of cancer. Even following successful curative treatment, patients often relapse, likely because of undetected micro-metastatic foci. Tumor-informed ctDNA testing has helped to identify those patients before they developed radiographic evidence of disease, introducing the concept of minimal residual disease (MRD) in solid tumors. No standard-of-care treatment options are available for MRD patients. Therefore, we have designed a phase IB trial of the combination of in vitro pre-activated and pre-expanded cord blood natural killer (pre-A+E CBNK) cells with cetuximab. We hypothesized that we could achieve CAR-like efficacy without genetic engineering, by pre-activating NK cells with inflammatory cytokines and by using antibodies to redirect NK cell specificity and antibody-dependent cellular cytotoxicity. The highly immunosuppressive CRC tumor microenvironment is understudied, and novel NK-cell therapy could be highly effective in MRD clearance. Methods: 15 patients with CRC-MRD were enrolled in this trial and completed treatment. All the patients received immunodepleting treatment prior to an infusion of pre-A+E CBNK cells, up to a dose of 1x10^8/kg. Patients were monitored inpatient for 24 hours after treatment for infusion-related reaction, and were then seen for toxicity follow-up in the outpatient clinic twice/week for 4 weeks (DLT window). Samples for correlative analysis were collected at different times. Results: 8/15 patients enrolled were female and 7 were male, age range 26-69. They all had no measurable radiographic evidence of disease and a positive ctDNA Signatera test at baseline. 11/15 were previously treated for metastatic disease; 13 patients had a history of metastases (including 7 liver, 2 lymph nodal, 2 peritoneal). All of them received 5-FU-based chemotherapy. 7/15 were RAS/RAF WT, 4/10 were KRAS mut, 1/10 had BRAF mutation, 1/10 had HER2 amplification. They were all pMMR. No DLT was observed, only 1 patient had G2 CRS requiring tocilizumab. 9/15 patients treated so far had ctDNA clearance at some point. One patient had negative ctDNA at 3 and 6 months, 4/15 were negative at d28 and 7/15 at d14. 4/15 patients have not met the 90-day time point yet. 10/12 patients analyzed up to the primary endpoint had decreased ctDNA over baseline CBNK cells in blood peaked 3 hours post-infusion and persisted at 3 days. Phenotype analysis of CBNK pre-post, donor NK and other immune cells is ongoing. Conclusions: Cetuximab in combination with pre-A+E CBNK is safe and showed promising results for the treatment of MRD-CRC. Clinical trial information: NCT050468 .