tbuckley/cabot-search huggingface dataset:
Updated survival results of ALTER-C002: Anlotinib combined with CAPEOX as first-line treatment in RAS/BRAF wild-type unresectable metastatic colorectal cancer.
Authors: Yue Liu, Kefeng Ding, Qian Xiao, Jinjie He, Hanguang Hu, Jinlin Du, Yuping Zhu, Jiaqi Chen, Zhuo Liu, Jianping Wang, Lifeng Sun, Dong Xu, Jun Li, Xiujun Liao, Jianwei Wang, Yibo Cai, Cheng Cai, Zhekang Jin, Ying Yuan
Journal: Journal of Clinical Oncology (2024)

131 Background: Anlotinib is an oral multi-target tyrosine kinase inhibitor, mainly targeting VEGFR 1-3, FGFR 1-4, PDGFR a/b and c-kit. Previous trial had demonstrated that anlotinib monotherapy was effective and safe in advanced colorectal cancer. ALTER-C002 trial is an open-label, single-arm, phase II study, aimed to evaluate the efficacy and safety of anlotinib plus CAPEOX as first-line therapy in patients with RAS/ BRAF wild-type unresectable metastatic colorectal cancer (mCRC). The progression-free survival has been reported, preliminary results demonstrated significant antitumor activity and manageable toxicity, here we reported the overall survival results at the data cutoff of May 29, 2023. Methods: RAS/BRAF wild-type unresectable mCRC patients with no prior systemic treatment received anlotinib (12 mg p.o. qd, d1-d14, q3w), capecitabine (850 mg/m 2 p.o., bid, d1-d14, q3w) and oxaliplatin (130 mg/m 2 i.v., d1, q3w) for 6 cycles followed by anlotinib and capecitabine as maintenance therapy until disease progression. Tumor response was assessed every 6 weeks according to RECIST v1.1 by investigator. The primary endpoint was ORR, and secondary endpoints included safety, DCR, DOR and PFS. Results: From Nov 2019 to February 2021, 30 eligible patients were enrolled, of whom, median age was 60y (range, 32-72y), 26 (86.7%) had left colon or rectal cancer, and 25 (83.3%) had liver metastases. In previous reports, ORR, DCR, and median PFS were 76.7%, 93.3%, and 11.3 months, respectively. At a Median follow-up of 31.7 months (95% CI, 27.8-35.6), the median OS was 29.7 months (95% CI, 21.2-38.2), the 24-month OS rate was 55.0% (95%CI, 35.4-70.9%) and the 30-month OS rate was 40.6% (95%CI:21.6-58.9%). Conclusions: Anlotinib combined with oxaliplatin and capecitabine achieved considerable OS and showed potential efficacy as first-line therapy for mCRC with manageable toxicity profiles. Clinical trial information: NCT04080843 .
The landscape of the comprehensive genomic profile for patients with bowel cancer.
Authors: Tatsuro Yamaguchi, Masachika Ikegami, Tomoyuki Aruga, Yusuke Kanemasa, Shin-ichiro Horiguchi, Akinari Takao, Misato Takao, Kazushige Kawai
Journal: Journal of Clinical Oncology (2024)

189 Background: The aim of study was to clarify the landscape of comprehensive genomic profile in bowel cancer. Methods: This study included 57,103 patients between June 1, 2019 and August 18, 2023 (version 20230821) with a nationwide retrospective design. Patients underwent one of three CGP tests, including OncoGuide, FoundationOne CDx (F1CDx), and FoundationOne Liquid (F1LCDx) CDx, at the physician's choice. We evaluated the pathogenicity of the detected variants based on the public database and gene function. Results: Of the 57,103 patients, 9,595 (16.8%) were bowel cancer, including 911 for OncoGuide, 7,711 for F1CDx and 810 for F1LCDx. In the tumor site, COADREAD was the most common bowel tumor, followed by SBC and APAD. TP53 was the most common gene with SNV/Indels, followed by APC, TP53, KRAS and PIK3CA. FLT3 was the most frequently amplified gene, followed by CDK8 and FLT1. For gene deletions, SMAD4 was the most frequently deleted gene, followed by PTEN and CDKN2A. For genomic rearrangements, EML4-ALK was the most common. A total of 46 (5.0%) germline pathogenic variants were identified in OncoGuide in mismatch repair genes in 12 patients, in BRCA1/2 genes in 11 patients, and in the APC gene in 7 patients. Conclusions: The detected variants should be re-annotated due to the inclusion of several benign variants in the CGP testing, and the landscape of the variants derived from these results in the CGP testing, including FoundationOne CDx, FoundationOne Liquid CDx, and OncoGuide, will help researchers and physicians interpret these results.
Real-world comparison of low- versus high-dose continuous 5FU infusion in patients receiving triplet chemotherapy plus bevacizumab for newly diagnosed metastatic colorectal cancer (mCRC).
Authors: William Joseph Chapin, Wei-Ting Hwang, Ronac Mamtani, Mark H. O'Hara
Journal: Journal of Clinical Oncology (2024)

62 Background: Several randomized trials demonstrated an overall survival (OS) benefit to triplet chemotherapy (5-FU, oxaliplatin, and irinotecan) plus bevacizumab compared to doublet chemotherapy plus bevacizumab in patients with newly diagnosed mCRC, though with higher rates of neutropenic fever and diarrhea. These trials used high-dose continuous infusion 5-FU (3,200 mg/m2/48 hours), but national guidelines suggest low-dose continuous infusion 5-FU (2,400mg/m2/48 hours) due to lower tolerance in U.S. patients. We performed a retrospective cohort study in a U.S. population to compare the effectiveness of low- vs high-dose continuous infusion 5FU in patients undergoing triplet chemotherapy plus bevacizumab for newly diagnosed mCRC. Methods: We used the nationwide Flatiron Health electronic health record-derived database, comprising de-identified patient-level structured and unstructured data curated via technology-enabled abstraction from ~280 cancer clinics. Patients with newly diagnosed mCRC who initiated triplet chemotherapy plus bevacizumab between 10/23/14 and 10/31/22 with non-missing height, weight, and dosing data were included. 5FU infusion doses of 2,000 – 2,799 mg/m2 were categorized as low-dose while those &gt;/= 2,800 mg/m2 were categorized as high-dose. OS from first-line treatment initiation was assessed by dosing group using the Kaplan Meier method with log-rank testing. Multivariable analysis with adjustment for pre-specified variables with imbalance (defined by standardized difference &lt; - 0.10 or &gt; 0.10) was performed using multivariable Cox proportional hazards modeling. Missing data were imputed using multiple imputation with chained equations. Results: Among 320 patients included, 244 received low-dose and 76 patients received high-dose continuous infusion 5FU. Imbalance between low- and high-dose groups was observed in the use of 5FU bolus (23% vs 3%), year of metastatic diagnosis 2018 - 2022 (80% vs 55%), mean irinotecan dose (156.4 vs 160.5 mg/m2), left-sided primary (73% vs 64%), MMR deficiency (3% vs 6%) and mean CEA (478 vs 691 µg/L). In univariate analysis, median OS was 33 months (95% CI 26 – 39) in the low-dose group compared to 34 months (95% CI 24 – 48) in the high-dose group (HR 1.16; 95% CI 0.79 – 1.69; p = 0.44). After adjusting for imbalanced covariates, there was no difference in hazard of death between low- and high-dose groups (HR 0.99; 95% CI 0.64 – 1.53; p = 0.97). Conclusions: In this real-world, U.S. population with newly diagnosed mCRC receiving triplet chemotherapy plus bevacizumab, there was no association with survival between low- vs high-dose continuous infusion 5FU. This supports current guidelines recommending low-dose continuous infusion 5FU (2,400mg/m2/48 hours) for patients with mCRC receiving triplet chemotherapy in the U.S.
Risk of second cancers in long term survivors of neuroendocrine tumors of the large intestine.
Authors: Callie Fort, Chaitra Surapaneni, Rakesh Surapaneni
Journal: Journal of Clinical Oncology (2024)

600 Background: There is an increasing incidence of neuroendocrine tumors (NET) of the colon and rectum likely related to increased screening colonoscopy and availability of better diagnostics. Most of these tumors identified during screening are low grade early-stage tumors with high cure rates. Data on long term risk of recurrence of NET and other second cancers is lacking. We studied the incidence rates of all second malignancies in survivors of NET of the colon and rectum. Methods: We analyzed data from the Surveillance, Epidemiology and End Results (SEER), Research Data 17 Registries, Nov 2022 Sub (2000-2022) to determine the risk of second malignancies in patients with an initial cancer diagnosis of NET of the colon and rectum. With these criteria we had overall 17,907 patients and 157,720 patient years of follow up. The relative risk of subsequent malignancies is reported as a standardized incidence ratio (observed incidence [O]/expected incidence [E]). Incidence ratios are analyzed over time from initial diagnosis to assess long term risk. Results: Survivors of NET of the large intestine are at highest risk of malignancy of the rectum (O/E: 6.4, CI: 7.26 - 5.61, N= 239) and this increased risk of rectal cancer persists even 10 years after the initial diagnosis (0/E: 3.8, CI: 5.37- 2.6, N= 32). There is no increased risk of cancer of the colon excluding rectum (O/E: 0.98, CI: 1.18-0.81, N= 114). Even after 10 years from diagnosis there is increased risk of second cancers for NET of the Colon (O/E: 1.28, CI: 1.55-1.06, N=110) and NET of the Rectum (O/E: 1.12, CI: 1.23- 1.02, N= 433). There is also increased incidence of small intestine cancer (O/E: 2.92, CI: 4.17- 1.97, N=30), Prostate cancer (O/E: 1.28, CI: 1.41- 1.15, N=400), Kidney and renal pelvis cancer (O/E: 1.53, CI: 1.86 -1.25, N= 104), Thyroid cancer (O/E: 1.63, CI: 2.12-1.23, N= 55) and Nodal Non-Hodgkins Lymphoma (O/E: 1.34, CI: 1.71-1.03, N=64). Conclusions: Survivors of NET of the large intestine are at risk of developing subsequent malignancies. The information presented may help physicians in effectively monitoring survivors for second cancers at various timeframes from their initial diagnosis.
Infusional fluorouracil and weekly docetaxel as first-line therapy for gastric cancer with bone marrow metastasis and disseminated intravascular coagulation: A multi-center, phase II trial (Zhen Long).
Authors: Jian Xiao, Xiaohui Zhai, Shanshan Li, Haibo Zhang, Yong Li, Jin Peng, Yisheng Huang, Lishuo Shi, Hailing Liu, Rongqin Zhang, Meiyu Hu, Xiaolin Pang, Xiaoru Lin
Journal: Journal of Clinical Oncology (2024)

337 Background: Gastric cancer (GC) with bone marrow metastasis (BMM) and disseminated intravascular coagulation (DIC) constitute a highly aggressive GC (HAGC) sub-type with distinctive features. The prognosis is poor and most HAGC patients die in weeks without effective treatment. Undue concerns about the myelosuppression mitigate against the application of cytotoxics in HAGC which is characterized by thrombocytopenia. Retrospective analysis showed low dose chemotherapy might relieve the DIC and bring with survival benefit but the standard of care (SOC) has not yet been established without a prospective study available. We completed a multi-center phase II trial evaluating the safety and efficacy of infusional fluorouracil and weekly docetaxel as first-line (1L) treatment for HAGC. Methods: This was a single-arm trial. A Simon's two-stage optimal design was applied. Eligible cases were: 18-75 years old, histologically confirmed GC, established BMM, overt DIC, platelet ≤ 50*10 9 /L and Eastern Cooperative Oncology Group (ECOG) performance status (PS) ≤ 3. Fluorouracil 200mg/m 2 /d continuous infusion on days 1-21 and docetaxel 25mg/m 2 /d on days 1, 8, 15 were given every four weeks. Hematological response (HeR) was defined as the platelet restored to normal range. The primary end point was HeR rate. Secondary end points were time to HeR (TTHeR), one month mortality (OMM), overall survival (OS), adverse events (AEs) and quality of life (QoL). Results: From Jan 2021 to Sep 2022, 24 HAGC cases from three Chinese centers were enrolled (details shown in table below). 20 HeRs were achieved and the HeR rate was 83.3%. Median TTHeR was 13 days and OMM was 12.5%. Till the data cut-off date (Jul 31, 2023), 3 patients were still alive with a median follow-up of 403 days. The median OS was 242 days. Totally, twelve Grade 3 AEs were recorded in 7 (29.2%) patients, among which stomatitis (4, 16.7%) and aminotransferase elevation (3, 12.5%) were the most frequent. No drug-related grade 4 or 5 AEs were observed. QoL outcomes were significantly improved both during and after the treatment. Conclusions: Anti-cancer treatment is the key point to control DIC of HAGC. The Zhen Long regimen was well tolerated and showed promising efficacy in the 1L setting. It should be considered as the SOC in current practice, but further randomized trials are still needed. Clinical trial information: NCT04547153 . [Table: see text]
Quality-adjusted time without symptoms of disease or toxicity (Q-TWiST) analysis of fruquintinib + best supportive care (BSC) compared with placebo + BSC in metastatic colorectal cancer (mCRC): Results from the FRESCO-2 trial.
Authors: Sebastian Stintzing, Josep Tabernero, Taroh Satoh, Arvind Dasari, Sara Lonardi, Cathy Eng, Rocio Garcia-Carbonero, Elena Elez, Takayuki Yoshino, Alberto F. Sobrero, James C. Yao, Stefan Kasper, Dirk Arnold, Edin Basic, Matthias Granold, Marco Petschulies, Liwen Wu, Lucy Chen, Zhao Yang, Eric Van Cutsem
Journal: Journal of Clinical Oncology (2024)

116 Background: As mCRC and its treatment can adversely impact quality of life (QoL), maintaining QoL is an important treatment goal in addition to improving survival outcomes, particularly as patients progress through lines of therapy. In the global, randomized, double-blind, phase 3 FRESCO-2 trial (NCT04322539), fruquintinib (F) + BSC vs placebo (P) + BSC demonstrated significantly improved overall survival (OS) (median 7.4 months vs 4.8 months; HR 0.66, 95% confidence interval [CI] 0.55–0.80) and progression-free survival, with a manageable safety profile and without deterioration of QoL in heavily pretreated patients with refractory mCRC. The objective of this post-hoc Q-TWiST analysis was to assess the quality-adjusted survival benefit of F + BSC in the context of the FRESCO-2 trial. Methods: The Q-TWiST analysis was applied to all 691 randomized patients from FRESCO-2 (F + BSC n=461 vs P + BSC n=230). Survival time of each patient was partitioned into 3 health states: time spent with treatment-emergent adverse events of CTCAE grade 3 or 4 before disease progression (TOX), time before disease progression without toxicity (TWiST), and time between disease progression and death or censoring (REL). Assuming utility coefficients of 1 for TWIST and 0.5 for TOX and REL, Q-TWiST was calculated as the utility-weighted sum of the time spent in each health state. The mean time spent in each of the 3 health states was calculated for each treatment group using Kaplan-Meier analysis, and a 95% CI for the difference between treatment was calculated using the nonparametric bootstrap method. Results: Q-TWiST was 6.25 months for F + BSC and 4.21 months for P + BSC, a difference of 2.04 (95% CI 1.51–2.57) months longer with F + BSC vs P + BSC. This difference in Q-TWiST was mainly driven by the difference in the TWiST component (2.14 months [95% CI 1.78–2.49]; F + BSC 4.06 months vs P + BSC 1.92 months). The relative Q-TWiST gain, calculated as the difference in Q-TWiST divided by the mean OS time of the P + BSC group, was 31.4% in favor of F + BSC. Conclusions: In the FRESCO-2 trial, F + BSC demonstrated a clinically meaningful quality-adjusted survival benefit compared with P + BSC in heavily pretreated patients with refractory mCRC. Clinical trial information: NCT04322539 .
Socioeconomic variables in the National Cancer Database: Utilization and impact of income and education in survival models for patients with resected pancreas cancer.
Authors: Qianyun Luo, Christopher James LaRocca, Jacob Ankeny, Eric Hans Jensen, Schelomo Marmor, David Brauer
Journal: Journal of Clinical Oncology (2024)

607 Background: The National Cancer Database (NCDB) is commonly used for analyzing survival outcomes in pancreatic cancer and has a robust number of patient-specific socioeconomic variables. Although these aggregated variables are commonly collected, their utility and impact on survival has infrequently been assessed. We aim to assess the distribution of income and education variables on their impact on survival models for patients who underwent resection for pancreatic ductal adenocarcinoma (PDAC). Methods: Patients undergoing definitive surgery for PDAC between 2004-2020 were identified from the NCDB. Variables of interest were income and education according to the patient’s ZIP code of residence. Pearson and Spearman correlation was assessed. Overall survival (OS) was calculated using Kaplan Meier method. The effects of income and education was calculated using Cox proportional Hazard (PH) models. Results: 69,362 patients met inclusion criteria. Median age was 66 (IQR 59-73), with 48.9% female. The correlation coefficient between income and education based on the 2020 American Community Survey data was 0.48 (p&lt;0.01). Median OS from the time of diagnosis was 21 months. The 5-year OS was 19.4 and 22.7 months for groups with lowest and highest education (p&lt;0.01). Group with missing education has a 5-year OS of 22.4 month, comparable to the group with highest education (p=0.82). The 5-year OS based on income quartiles was 18.7 and 22.5 months for the Q1 and Q4 (p&lt;0.01). Group with missing income has a 5-year OS of 22.4 month, similar to the highest income group (p=0.85). When including combinations of income, education and their interaction, the concordance of Cox models was changed by less than 0.002. Conclusions: For patients who underwent definitive surgery for PDAC, the income and education variables are only mildly correlated, and their inclusion do not have significant impact on OS models. Investigators should reconsider the utility of the aggregate NCDB measures, as they many not fully elucidate income and education disparities and impact on survival. [Table: see text]
Real-world data of TAS-102 therapy in refractory metastatic colorectal cancer (mCRC): The experience of the University Hospital of Montreal (CHUM).
Authors: Reem El Khoury, Jad Tehfe, Marie Ouellet, Francine Aubin, Rasmy Lougnarath, Jean-Pierre M. Ayoub, Mustapha Tehfe
Journal: Journal of Clinical Oncology (2024)

137 Background: Colorectal cancer poses a substantial healthcare burden due to its elevated rates of diagnosis and mortality. Managing refractory metastatic cases remains a challenge in our practice due to the paucity of therapeutic options. Treatment with Trifluridine-Tipiracil (TAS-102) prolonged overall survival among patients (pts) with mCRC. This study investigates the efficacy of TAS-102 therapy in this patient population and explores various prognostic factors influencing clinical outcomes. Methods: We retrospectively reviewed the data of 53 patients with refractory mCRC treated with at least 1 cycle of TAS-102 at CHUM between March 2018 and January 2023. Multivariate and univariate analyses were employed to evaluate the impact of age, number of prior treatments, presence of KRAS mutation, gender, tumor origin, and Eastern Cooperative Oncology Group (ECOG) performance status on progression-free survival (PFS) and overall survival (OS). Survival analysis was conducted using the Kaplan-Meier method, and Cox regression analysis assessed prognostic factors. Results: The median age was 61 years (23-82), and 27 pts (50.9%) were females. Twenty-two pts (41.5%) had their primary tumor located in the left colon, 17 pts (32.1%) had right-sided tumors, and 14 pts (26.4%) with rectal tumors. 52% of pts received TAS-102 after 2 lines of therapy and 43% beyond third line. The performance status was: ECOG 0/1 in 46 pts (86.8%), and ECOG 2 in 7 pts (13.2%). In our refractory mCRC pts, median PFS was 3 months and median OS 7 months. Univariate analysis demonstrated no significant differences in PFS or OS based on patient sex, KRAS mutation status, tumor sidedness, or the number of prior treatments. In univariate and multivariate analysis ECOG 0/1 pts compared to ECOG 2 pts had a significant improvement in both PFS (HR = 0.33; p = 0.0511) and OS (HR = 0.21; p = 0.0086). Conclusions: In our real-world experience, clinical outcomes were comparable to the findings from the RECOURSE trial, suggesting improved PFS and OS with TAS-102 in heavily pre-treated mCRC patients. ECOG performance status remains a significant prognostic factor and underscores its importance in treatment decisions for this patient population.
Clonal hematopoiesis of indeterminate potential (CHIP), treatment outcomes and adverse events in gastrointestinal cancers: A pooled analysis of clinical trial and real-world data.
Authors: Tharani Krishnan, Joao Paulo Solar Vasconcelos, Emma Titmuss, James Thomas Topham, David F. Schaeffer, Aly Karsan, Howard J Lim, Cheryl Ho, Sharlene Gill, Hagen Fritz Kennecke, Derek J. Jonker, Eric Xueyu Chen, Daniel John Renouf, Christopher J. O'Callaghan, Jonathan M. Loree
Journal: Journal of Clinical Oncology (2024)

169 Background: Clonal hematopoesis of indeterminate potential (CHIP) is the acquisition of somatic mutations leading to clonal expansion of hematopoietic stem cells and is a common incidental finding in circulating tumor DNA (ctDNA). Inflammation from these cells or a reduced marrow reserve may impact treatment outcomes or adverse events. We investigated the incidence of CHIP in ctDNA from patients with gastrointestinal (GI) cancers and explored its association with outcomes and adverse events (AEs). Methods: We collected ctDNA results from a local prospective metastatic colorectal cancer (mCRC) cohort (PREDICT-L) and ctDNA data from two randomized trials: CCTG CO.26 (durvalumab + tremelimumab [D+T] or best supportive care [BSC] in mCRC) and CCTG PA.7 (gemcitabine and nab-paclitaxel [GN] with or without D+T in metastatic pancreatic adenocarcinoma [mPDAC]). CHIP+ was defined as the presence of a variant of ≥2% variant allele frequency annotated in the ctDNA report in any of the genes DNMT3A, TET2, ASXL1 and ATM, and not annotated as germline by respective sequencing platforms. The first line of treatment after ctDNA was reviewed, and grade ≥3 or dose-limiting adverse events were documented. Results: The prevalence of CHIP varied from 10% to 18% (see table). CHIP+ patients were older than CHIP- in the CO.26 cohort (p=0.011), and ECOG was higher in CHIP+ patients in the PREDICT-L cohort. There was no difference between CHIP+/- patients with regards to sex. DNMT3A was the gene most frequently mutated in all three cohorts. There was no significant difference in PFS or OS between the CHIP+/- groups, both in those treated with chemotherapy (Chemo) or immunotherapy (IO). The most common AEs were rash, GI toxicities and bleeding/clotting abnormalities. There was no significant difference in the rates of AEs between the CHIP+/- groups for those treated with Chemo or IO. Conclusions: CHIP is a common alteration in ctDNA but did not impact PFS, OS, or the chance of developing an AE. [Table: see text]