tbuckley/cabot-search huggingface dataset:
Fruquintinib combined with FOLFIRI/mFOLFOX6 as second-line treatment in patients with RAS-mutant metastatic colorectal cancer (mCRC): A multicenter, open-label, phase II study.
Authors: Yun Xu, Yuchen Wu, Yuedi Dai, Xiaopin Ji, Zhe Cui, Xiaodong Zhu, Ye Xu
Journal: Journal of Clinical Oncology (2025)

151 Background: Anti-angiogenic drugs combined with chemotherapy could bring good clinical benefit to patients (pts) with mCRC, but the efficacy in pts with RAS mutant mCRC was limited. Fruquintinib is a highly selective oral inhibitor of vascular endothelial growth factor receptors (VEGFRs -1, -2, and -3) and was approved for previously treated mCRC. Our study was to explore the efficacy and safety of fruquintinib combined with FOLFIRI/mFOLFOX6 in the second line treatment of RAS-mutant mCRC (NCT05634590). Methods: Eligible pts with histologically confirmed RAS-mutant mCRC who had received first-line standard chemotherapy regimens were included in the study, and pts received Fru (4 mg, p.o. qd, 3 weeks on/1 week off, q4w) plus FOLFIRI/mFOLFOX6 (d1-15, q4w) until disease progression, unacceptable toxicities, or withdrew consent. The primary endpoint was progression-free survival (PFS). Secondary endpoints included objective response rate (ORR), disease control rate (DCR), overall survival (OS)and safety. Results: As of Aug 30, 2024, 25 eligible pts were enrolled and received at least one time treatment. Baseline characteristics included median age (66.0 [range: 35-73]), female/male (56.0% / 44.0%), ECOG PS 1(68.0%), left-sided and right-sided colon (72.0% / 28.0%), liver metastasis (64.0%), prior anti-VEGF therapies (76.0%). 14 pts had received at least one tumor assessment. Five pts achieved partial response (PR), 9 pts achieved stable disease (SD), and the ORR was 35.7% (5/14) (95% confidence interval [CI]: 12.8-64.9), the DCR was 100.0% (14/14) (95% CI: 76.8-100.0). Compared to liver metastases, the ORR was higher without liver metastases (42.9% [95%CI 9.9-81.6]). The median PFS was 6.41 months (95% CI: 6.37 - NA), and median OS was not reached yet. In the subgroup analysis, Median PFS was also longer without liver metastases pts than with liver metastases (8.84 mo vs 6.41 mo; HR=1.230; 95%CI 0.2462-6.148; p=0.7775). Additionally, Grade ≥3 treatment-emergent adverse events (TEAEs) included platelet count decreased (18.2%), hypertension (9.1%) and neutrophil count decreased (9.1%). Conclusions: Fruquintinib combined with FOLFIRI/mFOLFOX6 as second-line in patients with RAS-mutant mCRC achieved a promising clinical benefit, with a manageable safety profile. This trial is ongoing and more updated clinical data will be presented in the future. Clinical trial information: NCT05634590 .
Neoadjuvant therapy in T3 and T4 colon cancer: Is there a promising future?
Authors: Paola Pena, Aryanna Sousa, Qusai AlMasad, Steve Kwon
Journal: Journal of Clinical Oncology (2025)

144 Background: Neoadjuvant chemotherapy (NAC) is increasingly being considered over standard upfront surgery followed by adjuvant chemotherapy for locally advanced colon cancer. Studies have been underpowered to look at the impact of NAC on overall survival (OS) in individual clinical T stages. Methods: A nationwide retrospective analysis using the National Cancer Database to evaluate patients with clinical stage T3 and T4 colon adenocarcinomas from 2010 to 2020. Cox proportional hazards model was used to evaluate the impact of NAC approach compared to upfront surgery on OS. Clinical and pathological T stages were compared among those who underwent upfront surgery to evaluate accuracy of clinical T staging. Results: Total of 60,557 patients were identified - 2,313 patients undergoing NAC and 58,245 undergoing upfront surgery. In the past decade, use of NAC increased from 1.73% to 12.13%. In our multivariable survival analysis combining clinical T3 and T4 patients, we observed a worse OS in the NAC group (HR 1.16, 95% CI 1.07-1.26). We found no OS benefit for patients undergoing NAC approach for clinical stage T3 (HR 1.13, 95% CI 0.99-1.28) but found a significant OS benefit for patients undergoing NAC approach for clinical stage T4 (HR 0.85, 95% CI 0.77-0.95). We observed that clinical T4 stage was accurately staged in 90.48% with overstaging in 9.52%; clinical T3 stage was accurately staged in 95.24% with overstaging in 2.18% of patients. Conclusions: Our analysis demonstrated OS benefit of the NAC approach in T4 colon adenocarcinoma but not in T3. The study highlights the importance of evaluating survival benefit of NAC separately for T3 and T4 colon adenocarcinoma in future studies, and the challenges of accurate clinical staging of colon cancer for NAC planning.
First-line (1L) nivolumab (NIVO) plus chemotherapy (chemo) vs chemo in patients (pts) with advanced gastric cancer, gastroesophageal junction cancer, and esophageal adenocarcinoma (GC/GEJC/EAC): 5-year (y) follow-up of Chinese pts from CheckMate 649.
Authors: Lin Shen, Yuxian Bai, Xiaoyan Lin, Wei Li, Jufeng Wang, Xiaochun Zhang, Hongming Pan, Chunmei Bai, Li Bai, Ying Cheng, Jingdong Zhang, Haijun Zhong, Yi Ba, Wenwei Hu, Rui-Hua Xu, Weijian Guo, Shukui Qin, Nan Hu, Stephen McCraith, Tianshu Liu
Journal: Journal of Clinical Oncology (2025)

392 Background: NIVO + chemo demonstrated clinically meaningful survival benefit and an acceptable safety profile vs chemo in previously untreated Chinese pts with advanced GC/GEJC/EAC from CheckMate 649, consistent with the overall study population. 1L NIVO + chemo is currently approved for pts with advanced non-HER2+ GC/GEJC/EAC in China and other countries. We report 5-y results of NIVO + chemo vs chemo in Chinese pts from CheckMate 649. Methods: Adults with previously untreated, unresectable advanced or metastatic, non-HER2+ GC/GEJC/EAC were enrolled regardless of programmed death ligand 1 (PD-L1) expression. Randomized pts received NIVO + chemo, NIVO + ipilimumab, or chemo. Dual primary endpoints for NIVO + chemo vs chemo were overall survival (OS) and progression-free survival (PFS) by blinded independent central review (BICR) in pts with PD-L1 combined positive score (CPS) ≥ 5. Results: 208 Chinese pts were randomized to NIVO + chemo or chemo. At 61-month (mo) minimum follow-up, NIVO + chemo continued to demonstrate OS and PFS benefit vs chemo in pts with PD-L1 CPS ≥ 5 and all randomized pts (Table). 5-y OS rate was 24% with NIVO + chemo vs 8% with chemo in pts with PD-L1 CPS ≥ 5 and 20% vs 7% in all randomized pts. Objective response rate (ORR) was higher and responses were more durable with NIVO + chemo vs chemo in pts with PD-L1 CPS ≥ 5 and all randomized pts (Table). No new safety signals were identified with longer follow-up. Conclusions: NIVO + chemo continued to demonstrate clinically meaningful long-term survival benefit, more durable responses, and acceptable safety vs chemo in Chinese pts after 5 y of follow-up, consistent with earlier reports and with the overall study population of pts with advanced non-HER2+ GC/GEJC/EAC. These results further support NIVO + chemo as a standard 1L treatment option for Chinese pts. Clinical trial information: NCT02872116 . Efficacy PD-L1 CPS ≥ 5 All randomized NIVO + chemo(n = 75) Chemo (n = 81) NIVO + chemo (n = 99) Chemo (n = 109) mOS (95% CI), mo 15.5(11.9–21.1) 9.6(8.0–12.1) 14.3(11.5–16.5) 10.3(8.1–12.1) HR (95% CI) 0.57 (0.40–0.82) 0.63 (0.46–0.85) mPFS a (95% CI), mo 8.5(6.0–14.0) 4.3(4.1–6.5) 8.3(6.2–12.4) 5.6(4.2–6.8) HR (95% CI) 0.51 (0.34–0.76) 0.57 (0.41–0.80) ORR a,b (95% CI), % 68 (56–79) 48 (36–60) 66 (55–76) 45 (35–56) mDOR a,c (95% CI), mo 12.5 (7.2–23.4) 6.9 (3.9–8.5) 12.5 (7.2–17.7) 5.6 (4.4–8.3) a Per BICR. b In pts with measurable target lesions at baseline. c In responders. DOR, duration of response; m, median.
Short-course radiotherapy-based total neoadjuvant therapy combined with tislelizumab in the treatment of locally advanced rectal cancer (Neo-STAR): Early outcomes of a prospective, randomized phase II trial.
Authors: Fengpeng Wu, Linlin Xiao, Chaoxi Zhou, Wenbo Niu, Haiyan Fan, Hongqing Ma, Guanglin Wang, Jianfeng Zhang, Xuhua Hu, Jitao Hu, Guiying Wang
Journal: Journal of Clinical Oncology (2025)

150 Background: It has been found that radiotherapy possess synergistic anticancer effect with immune checkpoint inhibitors (ICIs). Therefore, this phase II randomized clinical trial (RCT) (ClinicalTrials.gov identifier: NCT05086627) aimed to evaluate the efficacy and safety of SCRT followed by CAPOX and tislelizumab in patients with LARC. Methods: Patients initially diagnosed rectal adenocarcinoma with cT1-2N+M0 or cT3-4NanyM0 were recruited, randomly assigned to receive SCRT (25Gy/5f), followed by four cycles of CAPOX combined with tislelizumab or CAPOX alone, respectively. After total mesorectal excision (TME), two cycles of postoperative adjuvant chemotherapy were given according to the patient's preferences. The pCR rate was set as the primary endpoint, and the major pathological response (MPR) (tumor regression grade (TRG) 0+1), 3-year progression free survival (PFS), 3-year overall survival (OS) and treatment safety were set as the secondary endpoints. R esults: Between September 2021 and March 2024, 118 patients were randomly assigned and 111 patients started allocated treatment, with 53 in the trial group and 58 in the control group. Ninety-six patients (86.5%) completed SCRT and 4 cycles of CAPOX chemotherapy with/without tislelizumab, including 49 patients (92.5%, 49/53) in the trial group and 47 patients (81.0%, 47/58) in the control group. Eighty-two patients (85.4%) had surgical resection, including 42 patients (85.7%, 42/49) in the trial group and 40 patients (85.1%, 40/47) in the control group. Among 82 patients who underwent surgery, 54.8% (23/42) patients in the trial group achieved pCR compared with 37.5% (15/40) in the control group. During the neoadjuvant treatment period, the incidence of grade 3-4 AEs were 9.4% in the trial group and 10.3% in the control group. Conclusions: SCRT-based TNT combined with tislelizumab followed by TME exhibited a favorable pCR rate in LARC. Clinical trial information: NCT05086627 . Surgical and postoperative pathological outcomes. Characteristic Experimental group (n= 42 ) Control group (n=4 0 ) R0 resection Yes 42 (100%) 40 (100%) No 0 (0%) 0 (0%) pCR Yes 23 (54.8%) 15 (37.5%) No 19 (45.2%) 25 (62.5%) TRG score 0 23 (54.8%) 15 (37.5%) 1 3 (7.1%) 2 (5%) 2 14 (33.3%) 15 (37.5%) 3 2 (4.8%) 8 (20%) Pathological T stage T0 24 (57.1%) 15 (37.5%) Tis 1 (2.4%) 0 (0%) T1 0 (0%) 1 (2.5%) T2 9 (21.4%) 6 (15%) T3 6 (14.3%) 10 (25%) T4 2 (4.8%) 8 (20%) Pathological N stage N0 39 (92.9%) 36 (90%) N1 3 (7.5%) 3 (7.5%) N2 0 (0%) 1 (2.5%) Type of surgery Anterior resection 36 (85.7%) 24 (60%) Abdominoperineal resection 6 (14.3%) 13 (32.5%) Hartmann procedure 0 (0%) 3 (7.5%) Anus preservation Yes 36 (85.7%) 27 (67.5%) No 6 (14.3%) 13 (32.5%)
Final analysis of the randomized phase 2 part of the ASPEN-06 study: A phase 2/3 study of evorpacept (ALX148), a CD47 myeloid checkpoint inhibitor, in patients with HER2-overexpressing gastric/gastroesophageal cancer (GC).
Authors: Kohei Shitara, Zev A. Wainberg, Josep Tabernero, Eric Van Cutsem, Clélia Coutzac, Christelle De La Fouchardiere, Jeeyun Lee, Sun Young Rha, Yoon-Koo Kang, Philip Fanning, Grace An, Feng Jin, Alison J Forgie, Jaume Pons, Athanasios Tsiatis, Sophia Randolph, Keun-Wook Lee
Journal: Journal of Clinical Oncology (2025)

332 Background: Evorpacept (Evo) is a high affinity, CD47-blocker with an inactive Fc region designed to safely magnify anticancer antibody dependent cellular phagocytosis. Evorpacept is being evaluated across cancers, in combination with anticancer antibodies and checkpoint inhibitors. Methods: The ASPEN-06 randomized phase 2 trial evaluates Evo in combination with standard trastuzumab (T), ramucirumab (R) and paclitaxel (P) for the treatment of patients with HER2+ GC. Patients with 2 nd or 3 rd line HER2+ advanced or metastatic GC that has progressed on or after prior anti-HER2 therapy were randomized to Evo (30 mg/kg Q2W) plus TRP or TRP. HER2 status was determined in the most recent GC tissue sample. Primary study objectives were to compare confirmed ORR of Evo-TRP to an assumed ORR of RP (=30%) with one-sided alpha error of 0.025 and to identify a clinically meaningful contribution of Evo to TRP in ORR (delta&gt;10%). Results: Among the entire randomized population (N=127) the ORR was 40.3% (Evo-TRP) and 26.6% (TRP), respectively. The difference between Evo-TRP's ORR compared to historical RP's ORR was not statistically significant (p=0.095), but Evo-TRP's ORR demonstrated a meaningful delta of 13.7% over TRP's ORR (p=0.028 in an exploratory analysis). Median DOR for Evo-TRP and TRP was 15.7 and 7.6 months, respectively. In a prespecified population with HER2+ disease in fresh tumor tissues after prior anti-HER2 treatment (N=48), Evo-TRP's ORR (54.8%) compared favorably to historical RP's ORR (p=0.030) with a delta of 31.7% over TRP's ORR of 23.1% (p=0.004 in an exploratory analysis). Evo-TRP was well tolerated with a safety profile consistent with prior experience. Updated results including PFS will be presented at the meeting. Conclusions: The addition of Evo to TRP showed promising activities in HER2+ GC. The magnitude of response was greatest in tumors identified as HER2+ using fresh biopsies emphasizing the importance of biopsies post anti HER2 therapy. Consistent with Evo’s mechanism of enhancing antibody dependent phagocytosis, these data support its ongoing investigation as an adjunct to anti-HER2 gastric cancer therapy. Clinical trial information: NCT05002127 .
Outcome of radiation related esophageal stricture from endoscopic dilation.
Authors: Yinghong Wang, Elliot Baerman, Carolina Colli Cruz, Samuel Black, Saivaroon Gajagowni, Brian Weston
Journal: Journal of Clinical Oncology (2025)

387 Background: Esophageal strictures present a significant challenge, particularly in cases of radiation-induced strictures. Esophageal dilation is a commonly used intervention aimed at improving swallowing function and nutritional status. However, radiation-induced strictures are amongst the most refractory to dilation. Understanding the success and limitations of this procedure is crucial for optimizing patient outcomes in the cancer population. Methods: This was a single-center retrospective chart review of 736 patients who received radiation as well as an EGD between 2014 and 2024. Patients without a radiation-induced stricture that was dilated were excluded. All continuous data are summarized as medians with interquartile ranges (IQR). Independent t-test was used for comparison among different groups. Results: 192 were eligible for this study. Our population was mostly male (58%) with a median age of 66 (IQR 67-74). The leading cancer diagnosis were esophageal (37%), head and neck (30.2%), and lung (17.1%). Radiation targets were head and neck (50.5%), lung (45.3%), both (1.6%), or other (1.6%). Patients were receiving active chemotherapy in 9.9% of cases. Mortality by the end of the study period was 51%. The median radiation dose was 5040 cGy (IQR 5040-6600) in a median of 28 fractions (IQR 26-33). Common indications for dilation were dysphagia (91.1%), weight loss (21.9%), and tube feed dependency (17.2%). Strictures were most often dilated 2 to 4 times (39.6%) to a median dilation size of 14 mm (IQR 12-15). Of note, 18.2% of patients needed 8 or more dilations. Dilation was associated with weight gain in 46.4% of patients, PEG tube removal in 3.1%, both forms of improvement in 9.9%, and no change in 40.6%. Complications included perforation (3.6%), aspiration pneumonia (3.6%), chest pain (0.5%), and hospitalization (0.5%). No significant differences were found in maximum dilation size, number of dilations, initial luminal diameter of the stricture, and initial length of the stricture between those who had clinical improvement as compared to those who did not. Conclusions: Our study reported 59.4% clinical improvement from esophageal dilation for radiation-induced strictures with nearly 20% of patients needing 8 or more dilations. The stricture dilation parameters did not appear to affect the success rate. This is the largest known single study of esophageal dilation for radiation-induced strictures.
Comparative analysis of demographics and outcomes in hospitalized patients with young- versus average-onset colorectal cancer in New York state (2017-2022).
Authors: Mrinalini Ramesh, Yasmin Fakhari-Tehrani, Vaishali Deenadayalan, Guangwei Yuan, Han Yu, Deepak Vadehra, Sarbajit Mukherjee
Journal: Journal of Clinical Oncology (2025)

27 Background: Recent studies have shown an increasing incidence of colorectal cancer (CRC) among young patients. This study investigates clinical outcomes and healthcare utilization among young (&lt;50) versus average onset (≥50) CRC patients admitted to hospitals in New York State (NYS). Methods: We performed a retrospective analysis using the Statewide Planning and Research Cooperative System (SPARCS) database from 2017 to 2022. Patients were divided into two groups: young-onset colorectal cancer patients (YOCRC, &lt;50 years) and average onset colorectal cancer patients (AOCRC, ≥50 years). The study population was further stratified by demographic and clinical characteristics. All associations were compared using the Kruskal-Wallis test, along with multivariate linear and logistic regression in RStudio version 4.4.1, at a significance level of ≤0.05. Clinical characteristics, including severity of illness and risk of mortality, were defined using the All Patient Refined (APR) grading system. Results: A total of 9,904 patients were identified (948 YOCRC and 8,956 AOCRC) with a primary admitting diagnosis of CRC from 2017 to 2022. In comparing the two age groups, AOCRC patients had a higher proportion of White, and female patients, whereas the YOCRC group included a higher proportion of Black and male patients (p&lt;0.001). The median length of stay was greater for AOCRC patients (5 days) compared to YOCRC patients (4 days), p&lt;0.001. Both age groups showed an upward trend in total cost of stay in the recent years. AOCRC patients were more likely to have increased severity of illness graded as major-extreme (60% vs 48%), while a higher proportion of YOCRC patients were classified as minor-moderate disease (51% vs 40%), p&lt;0.001. Similarly, AOCRC patients experienced a higher risk of mortality compared to YOCRC patients (p&lt;0.001). Regarding procedures, AOCRC patients needed more transfusions (13%) than YOCRC patients (9.3%), p&lt;0.001. YOCRC patients were also more likely to be discharged home (71% vs 46%), while AOCRC patients often required home health services or skilled nursing (p&lt;0.001). Notably, while the risk of mortality was higher for AOCRC patients, it has been decreasing overall from 2017 to 2022 [OR 0.92 (95% CI: 0.84-0.99), p=0.039]. Conclusions: AOCRC patients experienced greater severity of disease, higher mortality risk, and required more assistive care at discharge compared to YOCRC patients. The total cost of hospital stays has been rising for both groups. Policies focused on earlier outpatient interventions may help reduce the burden of inpatient care and rising costs.
MUC5AC levels as predictors of adjuvant therapy outcomes in pancreatic ductal adenocarcinoma: A study of post-surgical gemcitabine-based regimens.
Authors: Ashish Manne, Adam Khorasanchi, Amir Sara, Ankur Sheel, Lianbo Yu, Ashwini K. Esnakula
Journal: Journal of Clinical Oncology (2025)

759 Background: The role of tissue mucin 5 AC (MUC5AC) in PDA is not fully understood. In our previous work we showed that mature MUC5AC (MM) detected in the extracellular (EC) space and in apical region has better prognostic value than perinuclear immature MUC5AC (IM). Our previous research demonstrated that mature MUC5AC (MM), present in the extracellular (EC) space and apical region, offers better prognostic value than perinuclear immature MUC5AC (IM). Preclinical studies suggest that MM may confer chemoresistance to gemcitabine (Gem), commonly used in adjuvant therapy (AT) either alone or with capecitabine (Cap) or nab-paclitaxel (NP) in patients not eligible for FOLFIRINOX. This study investigates MM’s effect on outcomes in PDA patients undergoing post-surgical treatment with Gem-only, Gem-NP, and Gem-Cap. Methods: Formalin-fixed, paraffin-embedded tissue samples from resected PDA cases (January 2010 - June 2021) were sourced from the Ohio State University biorepository. Immunohistochemistry using monoclonal antibodies 45M1 (for MM) and CLH2 (for IM) was employed to examine cellular MM and IM expression, with H-scores calculated. Statistical analysis of progression-free survival (PFS) and overall survival (OS) was done using the log-rank test. Results: We had 49 patients available for analysis. The median age of the group was 66 years (range: 38 to 89) with majority Caucasians (90%) and 53% (n=26) females. AT distribution within this group was, 31 Gem-only, 7 Gem-NP, and 11 Gem and capecitabine (Cap). Median expression levels for MM and IM were both 150, and 82% (n=40) were EC-MM positive. Using the median MM H-score as a threshold (&lt; 150 vs. ≥ 150), outcomes were evaluated within each therapy subgroup (Table). Conclusions: This preliminary study suggests that PDA patients with low MM expression may benefit from Gem-Cap therapy. However, larger, prospective studies are needed for definitive conclusions. Comparing outcomes in the sub-groups. Sub-group (n) OS in days (p-value) PFS in days (p-value) MM H-score &lt; 150 vs. ≥ 150 Gem-only (11 vs. 20) 775 vs. 1006 (0.4) 444 vs. 413 (0.4) Gem NP (4 vs. 3) 1409 vs. 551 (0.8) 391 vs. 418 (0.5) Gem-Cap (4 vs. 7) not evaluable (NE) vs. 766 (0.02) NE vs. 415 (0.01)