Clinical colorectal cancer最新文献

{"title":"Patient-reported Bowel Function and Bowel-related Quality of Life After Pelvic Radiation for Rectal Adenocarcinoma: The Impact of Radiation Fractionation and Surgical Resection","authors":"Michael K. Rooney ,&nbsp;Brian De ,&nbsp;Kelsey Corrigan ,&nbsp;Grace L. Smith ,&nbsp;Cullen Taniguchi ,&nbsp;Bruce D. Minsky ,&nbsp;Ethan B. Ludmir ,&nbsp;Eugene J. Koay ,&nbsp;Prajnan Das ,&nbsp;Albert C. Koong ,&nbsp;Oliver Peacock ,&nbsp;George Chang ,&nbsp;Y. Nancy You ,&nbsp;Van K. Morris ,&nbsp;Graciela Nogueras-González ,&nbsp;Emma B. Holliday","doi":"10.1016/j.clcc.2023.02.003","DOIUrl":"10.1016/j.clcc.2023.02.003","url":null,"abstract":"<div><h3>Introduction</h3><p><span>Multimodality treatment for locally advanced </span>rectal cancer (LARC) can include long-course radiotherapy (LCRT) or short course radiotherapy (SCRT). Nonoperative management is increasingly pursued for those achieving a complete clinical response. Data regarding long-term function and quality-of-life (QOL) are limited.</p></div><div><h3>Methods</h3><p><span><span>Patients with LARC treated with radiotherapy from 2016 to 2020 completed the Functional Assessment of Cancer Therapy- General (FACT-G7), the Low Anterior Resection Syndrome Score (LARS) and the </span>Fecal Incontinence QOL Scale (FIQOL). Univariate and multivariable </span>linear regression analyses identified associations between clinical variables including radiation fractionation and the use of surgery versus non-operative management.</p></div><div><h3>Results</h3><p>Of 204 patients surveyed, 124 (60.8%) responded. Median (interquartile range) time from radiation to survey completion was 30.1 (18.3-43) months. Seventy-nine (63.7%) respondents received LCRT, and 45 (36.3%) received SCRT; 101 (81.5%) respondents underwent surgery, and 23 (18.5%) pursued nonoperative management. There were no differences in LARS, FIQoL or FACT-G7 between patients receiving LCRT versus SCRT. On multivariable analysis, only nonoperative management was associated with lower LARS score signifying less bowel dysfunction. Nonoperative management and female sex were associated with a higher FIQoL score signifying less disruption and distress from fecal incontinence issues. Finally, lower BMI at the time of radiation, female sex, and higher FIQoL score were associated with higher FACT-G7 scores signifying better overall QOL.</p></div><div><h3>Conclusions</h3><p>These results suggest long-term patient-reported bowel function and QOL may be similar for individuals receiving SCRT and LCRT for the treatment of LARC, but nonoperative management may lead to improved bowel function and QOL.</p></div>","PeriodicalId":10373,"journal":{"name":"Clinical colorectal cancer","volume":"22 2","pages":"Pages 211-221"},"PeriodicalIF":3.4,"publicationDate":"2023-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10213111/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10030906","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Optimizing Screening for Colorectal Cancer: An Algorithm Combining Fecal Immunochemical Test, Blood-Based Cancer-Associated Proteins and Demographics to Reduce Colonoscopy Burden","authors":"Mathias M. Petersen ,&nbsp;Jakob Kleif ,&nbsp;Lars N. Jørgensen ,&nbsp;Jakob W. Hendel ,&nbsp;Jakob B. Seidelin ,&nbsp;Mogens R. Madsen ,&nbsp;Jesper Vilandt ,&nbsp;Søren Brandsborg ,&nbsp;Jørn S. Rasmussen ,&nbsp;Lars M. Andersen ,&nbsp;Ali Khalid ,&nbsp;Linnea Ferm ,&nbsp;Susan H. Gawel ,&nbsp;Frans Martens ,&nbsp;Berit Andersen ,&nbsp;Morten Rasmussen ,&nbsp;Gerard J. Davis ,&nbsp;Ib J. Christensen ,&nbsp;Christina Therkildsen","doi":"10.1016/j.clcc.2023.02.001","DOIUrl":"10.1016/j.clcc.2023.02.001","url":null,"abstract":"<div><h3>Background</h3><p>Fecal Immunochemical Test (FIT) is widely used in population-based screening for colorectal cancer (CRC). This had led to major challenges regarding colonoscopy capacity. Methods to maintain high sensitivity without compromising the colonoscopy capacity are needed. This study investigates an algorithm that combines FIT result, blood-based biomarkers associated with CRC, and individual demographics, to triage subjects sent for colonoscopy among a FIT positive (FIT⁺) screening population and thereby reduce the colonoscopy burden.</p></div><div><h3>Materials and methods</h3><p>From the Danish National Colorectal Cancer Screening Program, 4048 FIT⁺ (≥100 ng/mL Hemoglobin) subjects were included and analyzed for a panel of 9 cancer-associated biomarkers using the ARCHITECT <em>i</em>2000. Two algorithms were developed: 1) a predefined algorithm based on clinically available biomarkers: FIT, age, CEA, hsCRP and Ferritin; and 2) an exploratory algorithm adding additional biomarkers: TIMP-1, Pepsinogen-2, HE4, CyFra21-1, Galectin-3, B2M and sex to the predefined algorithm. The diagnostic performances for discriminating subjects with or without CRC in the 2 models were benchmarked against the FIT alone using logistic regression modeling.</p></div><div><h3>Results</h3><p>The discrimination of CRC showed an area under the curve (AUC) of 73.7 (70.5-76.9) for the predefined model, 75.3 (72.1-78.4) for the exploratory model, and 68.9 (65.5-72.2) for FIT alone. Both models performed significantly better (<em>P</em> &lt; .001) than the FIT model. The models were benchmarked vs. FIT at cutoffs of 100, 200, 300, 400, and 500 ng/mL Hemoglobin using corresponding numbers of true positives and false positives. All performance metrics were improved at all cutoffs.</p></div><div><h3>Conclusion</h3><p>A screening algorithm including a combination of FIT result, blood-based biomarkers and demographics outperforms FIT in discriminating subjects with or without CRC in a screening population with FIT results above 100 ng/mL Hemoglobin.</p></div>","PeriodicalId":10373,"journal":{"name":"Clinical colorectal cancer","volume":"22 2","pages":"Pages 199-210"},"PeriodicalIF":3.4,"publicationDate":"2023-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9728330","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The Role of Immunotherapy in Esophageal and Gastric Cancer","authors":"Hans Dedecker ,&nbsp;Laure-Anne Teuwen ,&nbsp;Timon Vandamme ,&nbsp;Andreas Domen ,&nbsp;Hans Prenen","doi":"10.1016/j.clcc.2023.03.001","DOIUrl":"10.1016/j.clcc.2023.03.001","url":null,"abstract":"<div><p><span><span>Upper gastrointestinal tract tumors<span><span> historically have a poor prognosis. The decision to treat esophageal or gastric cancers by surgery, radiotherapy, systemic therapy, or a combination of these treatment modalities should always be discussed multidisciplinary. The introduction of </span>immunotherapy has drastically transformed the treatment landscape of multiple solid </span></span>malignancies. Emerging data from early and late phase </span>clinical trials<span> suggests that the use of immunotherapies that target immune checkpoint proteins such as PD-1/PD-L1 result in superior overall survival in advanced, metastatic, or recurrent esophageal and gastric cancer, whether or not with specific molecular characteristics such as PD-L1 expression level or microsatellite instability. This review offers an overview of the most recent advances in the field of immunotherapy treatment in esophageal and gastric cancer.</span></p></div>","PeriodicalId":10373,"journal":{"name":"Clinical colorectal cancer","volume":"22 2","pages":"Pages 175-182"},"PeriodicalIF":3.4,"publicationDate":"2023-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9728821","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Napabucasin Plus FOLFIRI in Patients With Previously Treated Metastatic Colorectal Cancer: Results From the Open-Label, Randomized Phase III CanStem303C Study","authors":"Manish A. Shah ,&nbsp;Takayuki Yoshino ,&nbsp;Niall C. Tebbutt ,&nbsp;Axel Grothey ,&nbsp;Josep Tabernero ,&nbsp;Rui-Hua Xu ,&nbsp;Andres Cervantes ,&nbsp;Sang Cheul Oh ,&nbsp;Kensei Yamaguchi ,&nbsp;Marwan Fakih ,&nbsp;Alfredo Falcone ,&nbsp;Christina Wu ,&nbsp;Vi K. Chiu ,&nbsp;Jiri Tomasek ,&nbsp;Johanna Bendell ,&nbsp;Marilyn Fontaine ,&nbsp;Matthew Hitron ,&nbsp;Bo Xu ,&nbsp;Julien Taieb ,&nbsp;Eric Van Cutsem","doi":"10.1016/j.clcc.2022.11.002","DOIUrl":"10.1016/j.clcc.2022.11.002","url":null,"abstract":"<div><h3>Purpose</h3><p><span><span>Napabucasin is an investigational, orally administered </span>reactive oxygen species generator bioactivated by intracellular antioxidant NAD(P)H:quinone oxidoreductase 1 that has been evaluated in various </span>solid tumors<span><span>, including metastatic colorectal cancer (mCRC). Phosphorylated </span>signal transducer and activator of transcription 3 (pSTAT3) is hypothesized to predict response in napabucasin-treated patients with mCRC.</span></p></div><div><h3>Patient and Methods</h3><p><span><span><span>In the multi-center, open-label, phase III CanStem303C (NCT02753127) study, adults with histologically confirmed mCRC that progressed on first-line fluoropyrimidine plus </span>oxaliplatin ± </span>bevacizumab were randomized to twice-daily napabucasin plus FOLFIRI (napabucasin) or FOLFIRI alone (control). The primary endpoint was overall survival (OS) in the general study population and </span>in patients with pSTAT3-positive tumors (biomarker-positive).</p></div><div><h3>Results</h3><p>In the general study population (napabucasin, n = 624; control, n = 629), median OS was 14.3 months for napabucasin and 13.8 months for control (hazard ratio [HR], 0.976, one-sided <em>P</em> = .74). Overall, 44% of patients were biomarker-positive (napabucasin, n = 275; control, n = 272). In the biomarker-positive population, median OS was 13.2 months for napabucasin and 12.1 months for control (HR, 0.969; one-sided <em>P</em> &gt; .99). In the control arm, median OS was shorter for biomarker-positive versus biomarker negative patients (12.1 vs. 18.5 months; HR, 1.518; nominal 2-sided <em>P</em><span> = .0002). The most common treatment-emergent adverse events (TEAEs) were diarrhea (napabucasin, 84.6%; control, 53.9%), nausea (60.5%, 50.5%), vomiting (41.2%, 29.3%), and abdominal pain (41.0%, 25.2%). Grade ≥3 TEAEs occurred in 73.8% of napabucasin-treated and 66.7% of control-treated patients, most commonly diarrhea (21.2%, 7.0%), neutrophil count decreased (13.7%, 19.2%), and neutropenia (13.3%, 15.2%). Safety was similar in biomarker-positive patients.</span></p></div><div><h3>Conclusion</h3><p>In patients with previously treated mCRC, adding napabucasin to FOLFIRI did not improve OS. Results from the control arm indicate that pSTAT3 is an adverse prognostic factor in mCRC.</p></div>","PeriodicalId":10373,"journal":{"name":"Clinical colorectal cancer","volume":"22 1","pages":"Pages 100-110"},"PeriodicalIF":3.4,"publicationDate":"2023-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9522261","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Sarcopenia is Associated With Oncological Prognosis and the Incidence of Secondary Cancer in Patients With Middle/Lower Rectal Cancer","authors":"Shinya Abe,&nbsp;Hiroaki Nozawa,&nbsp;Kazuhito Sasaki,&nbsp;Koji Murono,&nbsp;Shigenobu Emoto,&nbsp;Yuichiro Yokoyama,&nbsp;Hiroyuki Matsuzaki,&nbsp;Yuzo Nagai,&nbsp;Yuichiro Yoshioka,&nbsp;Takahide Shinagawa,&nbsp;Hirofumi Sonoda,&nbsp;Soichiro Ishihara","doi":"10.1016/j.clcc.2022.10.001","DOIUrl":"10.1016/j.clcc.2022.10.001","url":null,"abstract":"<div><h3>Objective</h3><p>This study evaluated the clinical implications of sarcopenia<span> for patients with rectal cancer according to cancer progression.</span></p></div><div><h3>Summary Background Data</h3><p>The negative impact of body composition on long-term outcome has been demonstrated for various malignancies.</p></div><div><h3>Methods</h3><p><span><span>We retrospectively reviewed 708 patients with rectal cancer who underwent curative resection at our institution between 2003 and 2020. Factors contributing to long-term outcomes and the incidence of secondary cancer (ISC) were analyzed. </span>Psoas muscle<span> mass index (PMI) was assessed using preoperative computed tomography. Sarcopenia was defined using the PMI cut-off values for Asian adults (6.36 cm</span></span>²/m² for males and 3.92 cm2/m2 for females).</p></div><div><h3>Results</h3><p><span>Sarcopenia was identified in 306 patients (43.2%). Sarcopenia was associated with advanced age, low body mass index<span>, smoking history, and advanced T-stage. Multivariate analysis<span> showed sarcopenia was an independent poor prognostic factor for OS (HR 1.71; </span></span></span><em>P</em> = .0102) and cancer-specific survival (HR 1.64; <em>P</em><span> = .0490). Patients with sarcopenia had significantly higher mortality due to cancer-related death in stages III and IV, whereas non-rectal cancer-related death, including secondary cancer, was markedly increased in stage 0-II sarcopenic rectal patients. Five-year cumulative ISC in patients<span> with and without sarcopenia was 11.8% and 5.9%, respectively. Multivariate analysis revealed that sarcopenia was an independent predictive factor for ISC (HR 2.05; </span></span><em>P</em> = .0063).</p></div><div><h3>Conclusions</h3><p>Sarcopenia helps predict survival outcomes and cause of death according to cancer stage for patients with middle/lower rectal cancer who underwent radical surgery. Furthermore, sarcopenia increased the development of secondary cancer in those patients.</p></div>","PeriodicalId":10373,"journal":{"name":"Clinical colorectal cancer","volume":"22 1","pages":"Pages 143-152"},"PeriodicalIF":3.4,"publicationDate":"2023-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9152361","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Trajectory for the Regulatory Approval of a Combination of Pertuzumab Plus Trastuzumab for Pre-treated HER2-positive Metastatic Colorectal Cancer Using Real-world Data","authors":"Yasutoshi Sakamoto ,&nbsp;Hideaki Bando ,&nbsp;Yoshiaki Nakamura ,&nbsp;Hiromi Hasegawa ,&nbsp;Takako Kuwaki ,&nbsp;Wataru Okamoto ,&nbsp;Hiroya Taniguchi ,&nbsp;Yoshihiro Aoyagi ,&nbsp;Izumi Miki ,&nbsp;Hiroshi Uchigata ,&nbsp;Naomi Kuramoto ,&nbsp;Nozomu Fuse ,&nbsp;Takayuki Yoshino ,&nbsp;Atsushi Ohtsu","doi":"10.1016/j.clcc.2022.10.003","DOIUrl":"10.1016/j.clcc.2022.10.003","url":null,"abstract":"<div><p><span>Utilizing real-world data (RWD) for effective clinical implementation is becoming more and more appealing as the cost of drug<span><span> development rises, especially for patients with rare diseases and rare molecular subtypes for whom conducting randomized controlled trials<span><span> is challenging. If a regulatory approval methodology based on RWD as an external control group can be established, drug development for rarer fractions can be accelerated by lowering costs and time, as well as reducing physical and emotional burdens on both patients and healthcare professionals. Since 2017, we have been prospectively collecting the clinical data of standard therapies </span>in patients with rare molecular fractions under the SCRUM-Japan Registry platform, which is a qualified registry utilized as external control data for regulatory submission. Based on the results of the phase II TRIUMPH study (UMIN000027887) and the extracted data from the SCRUM-Japan Registry, the pharmaceutical company submitted an application for </span></span>pertuzumab<span> and trastuzumab in patients with HER2-positive </span></span></span>metastatic colorectal cancer<span> in April 2021. Pertuzumab and trastuzumab were approved as expanded indications on March 28, 2022, as 6 cases out of 14 extracted from the SCRUM-Japan Registry were classified and utilized as “evaluation material” under the review process of the Pharmaceuticals and Medical Devices Agency (PMDA). Through the TRIUMPH study and the SCRUM-Japan Registry, we have paved the way for regulatory approval of RWD in Japan. In future, we must define the steps for constructing regulatory-grade registries and the method/process for utilizing RWD by accumulating case experiences.</span></p></div>","PeriodicalId":10373,"journal":{"name":"Clinical colorectal cancer","volume":"22 1","pages":"Pages 45-52"},"PeriodicalIF":3.4,"publicationDate":"2023-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9146209","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Unusual dMMR Phenotype Locally Advanced Pancreatic Ductal Adenocarcinoma with Germline and Somatic BRCA2 Mutation in a Jehovah Witness Patient","authors":"Mehmet Sitki Copur ,&nbsp;Soe Min Tun ,&nbsp;Luciano Vargas ,&nbsp;Shaheed Merani ,&nbsp;Whitney Wedel ,&nbsp;Randy Duckert ,&nbsp;Adam Horn ,&nbsp;Nicholas Lintel ,&nbsp;Daniel Herold ,&nbsp;Swathi Lavudi","doi":"10.1016/j.clcc.2022.10.002","DOIUrl":"10.1016/j.clcc.2022.10.002","url":null,"abstract":"<div><p></p><ul><li><span>•</span><span><p>PDAC<span> is a genetically heterogenous disease with various molecular subtypes which may explain variations in treatment response. Genetic mutations and altered molecular pathways serve as targets in therapy and may improve outcomes.</span></p></span></li><li><span>•</span><span><p>Neoadjuvant systemic therapy with or without radiation followed by evaluation for surgery is an accepted treatment approach for locally advanced disease with the goal of enabling an R0 resection to achieve improved disease-free and overall survival.</p></span></li><li><span>•</span><span><p>In many cancers, including pancreatic cancer<span><span><span><span>, MSI is a predictive biomarker for response to </span>immunotherapy, and a </span>prognostic factor for survival. Treatment with neoadjuvant </span>chemoimmunotherapy in this group of patients usually leads to pathologic complete responses.</span></p></span></li><li><span>•</span><span><p><span>Although rare (15%), an unusual dMMR phenotype, evidenced by discordance between </span>IHC<span> staining of MMR proteins and next gen sequencing, do exist. In this group of patients available data show varying responses to immunotherapy ranging from complete, to partial responses to stable disease.</span></p></span></li><li><span>•</span><span><p>We present successful treatment outcome in a locally advanced PDAC case with dMMR and germline plus somatic BRCA2<span> mutation treated with available chemotherapy immunotherapy and targeted therapy options.</span></p></span></li></ul></div>","PeriodicalId":10373,"journal":{"name":"Clinical colorectal cancer","volume":"22 1","pages":"Pages 160-165"},"PeriodicalIF":3.4,"publicationDate":"2023-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9146692","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"ROCKET: Phase II Randomized, Active-controlled, Multicenter Trial to Assess the Safety and Efficacy of RRx-001 + Irinotecan vs. Single-agent Regorafenib in Third/Fourth Line Colorectal Cancer","authors":"Tony R. Reid ,&nbsp;Nacer Abrouk ,&nbsp;Scott Caroen ,&nbsp;Bryan Oronsky ,&nbsp;Meaghan Stirn ,&nbsp;Christopher Larson ,&nbsp;Keola Beale ,&nbsp;Susan J. Knox ,&nbsp;George Fisher","doi":"10.1016/j.clcc.2022.11.003","DOIUrl":"10.1016/j.clcc.2022.11.003","url":null,"abstract":"<div><h3>Introduction</h3><p>RRx-001 is a novel cysteine-targeted alkylating agent that releases nitric oxide (NO). The primary biological activities of this hybrid molecule include macrophage repolarizing and vascular normalization. The purpose of this clinical trial (ROCKET) (NCT02096354) was to compare the safety and efficacy of the combination therapy RRx-001 + irinotecan vs. regorafenib in third/fourth line colorectal cancer that previously received treatment with irinotecan.</p></div><div><h3>Patients and Methods</h3><p>A total of 34 patients were randomized (24 to RRx-001 + irinotecan (RxI) and 10 to single-agent regorafenib (RegI)) and were the basis for the intention-to-treat analysis (ITT, comprising all 34 patients). RRx-001 treatment was administered as an up-to-2-month “primer” followed by irinotecan for patients randomized to the RRx-001 arm (24). The efficacy and safety data are presented for the 34 patients in the (ITT) efficacy analysis. Therapy consisted of intravenous administration of RRx-001 at 4 mg once weekly for up to 2 months, at which point RRx-001 was discontinued, followed by intravenous infusion of irinotecan at 180 mg/m² on day 1 in a 21-day cycle vs. 160 mg oral regorafenib daily for 3/4 weeks followed at progression, if applicable, by irinotecan 180 mg/m² on day 1 in a 21-day cycle. There were 3 patients (3/24 = 12.5%) with prior single agent irinotecan on the RRx-001 randomized arm and 2 (2/10 = 20%) on the regorafenib randomized arm. Numerous patients had irinotecan combination therapies prior to randomized treatment. There were 15 patients on RRx-001 arm that received irinotecan post-RRx-001 in the randomized trial. There were 5 PRs on RRx-001 plus irinotecan leading to an overall response of 20.8% (5/24). There were 37.5% (9/24) of RRx-001 randomized patients with KRAS mutant type while 60% (6/10) regorafenib randomized patients were of KRAS type mutant. There were only 4 patients with available QOL and Edmonton Symptom Assessment System, an insufficient sample size to allow for any meaningful analysis.</p></div><div><h3>Results</h3><p>Median patient follow-up was approximately 14.5 months (SD 4.5 months). Median overall survival was 8.6 months for RxI and 4.7 months for RegI. Median progression free survival was 6.1 months for RxI vs. 1.7 months for RegI (a statistically significant result, 2-sided log-rank test, <em>P</em> = .0030). The toxicity profile of RxI was substantially improved compared with RegI.</p></div><div><h3>Conclusion</h3><p>The results of this trial demonstrate improved efficacy of RxI compared with RegI in patients with metastatic colorectal cancer after previous treatment with irinotecan, and late-stage clinical development in this indication is planned on the strength of the observed “signal” accompanied by a sufficient safety profile.</p></div>","PeriodicalId":10373,"journal":{"name":"Clinical colorectal cancer","volume":"22 1","pages":"Pages 92-99"},"PeriodicalIF":3.4,"publicationDate":"2023-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9159846","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Molecular Residual Disease-guided Adjuvant Treatment in Resected Colorectal Cancer: Focus on CIRCULATE-Japan","authors":"Seiya Sato ,&nbsp;Yoshiaki Nakamura ,&nbsp;Eiji Oki ,&nbsp;Takayuki Yoshino","doi":"10.1016/j.clcc.2022.12.001","DOIUrl":"10.1016/j.clcc.2022.12.001","url":null,"abstract":"<div><p>The body of evidence supporting the utility of the detection of molecular residual disease (MRD) in resected colorectal cancer (CRC) using circulating tumor DNA (ctDNA) analysis is rapidly growing. Furthermore, this evidence provides the rationale for escalation and de-escalation adjuvant chemotherapy (ACT) strategies using ctDNA MRD analysis. This has led to various randomized clinical trials, and CIRCULATE-Japan is one of the largest of these trial platforms. In this review, we provide an overview of the potential utility of ctDNA-based MRD detection for escalation and de-escalation ACT approaches. Furthermore, we highlight the feasibility using ctDNA clearance as a surrogate endpoint for ACT trials in patients with resected CRC, based on findings of the CIRCULATE-Japan project.</p></div>","PeriodicalId":10373,"journal":{"name":"Clinical colorectal cancer","volume":"22 1","pages":"Pages 53-58"},"PeriodicalIF":3.4,"publicationDate":"2023-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9152880","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"An Exploration of Trifluridine/Tipiracil Monotherapy and in Combination With Bevacizumab or Immune Checkpoint Inhibitors for Patients With Metastatic Colorectal Cancer: A Real-World Study","authors":"Caiyun Nie ,&nbsp;Weifeng Xu ,&nbsp;Beibei Chen ,&nbsp;Huifang Lv ,&nbsp;Jianzheng Wang ,&nbsp;Yingjun Liu ,&nbsp;Yunduan He ,&nbsp;Saiqi Wang ,&nbsp;Jing Zhao ,&nbsp;Xiaobing Chen","doi":"10.1016/j.clcc.2022.11.005","DOIUrl":"10.1016/j.clcc.2022.11.005","url":null,"abstract":"<div><h3>Background</h3><p><span><span>Trifluridine/tipiracil (TAS-102) has achieved modest efficacy in the late-line treatment of </span>metastatic colorectal cancer. The present study aimed to explore the clinical efficacy and </span>drug toxicities of TAS-102 for patients with metastatic colorectal cancer in real-world clinical setting.</p></div><div><h3>Methods</h3><p><span><span>From October 2020 to February 2022, patients with metastatic colorectal cancer who failed from 2 or more lines of prior therapy and treated with TAS-102 monotherapy, in combination with </span>bevacizumab<span> or immune checkpoint inhibitors (ICIs) were analyzed. The evaluation indicators were </span></span>progression free survival (PFS), objective response rate , disease control rate (DCR), overall survival (OS) and drug toxicities.</p></div><div><h3>Results</h3><p>A total of 70 patients were enrolled. The objective response rate and DCR were 1.4% and 68.6%. The median PFS and OS were 6.0 (95% CI: 4.1-7.9) and 10.0 (95% CI: 8.3-11.7) months. Compared with TAS-102 monotherapy and TAS-102 plus ICIs, TAS-102 plus bevacizumab obtained superior DCR (75.9% vs. 50% vs. 40%, <em>P</em> = .047), PFS (6.3m vs. 3.0 m vs. 3.0 m, <em>P</em> = .041) and OS (12.0 m vs. 6.5 m vs. 6.0m, <em>P</em><span><span> = .013). Patients without prior regorafenib or </span>fruquintinib therapy obtained better median PFS (6.3 vs. 4.3 m, </span><em>P</em> = .031) and OS (NR vs. 9.0 m, <em>P</em><span><span> = .036). Other indicators, including age, tumor site, KRAS status and use of fluoropyrimidine as last regimen before TAS-102, did not affect the clinical efficacy of TAS-102. The most frequent adverse events were </span>leukopenia, neutropenia, anemia, fatigue, nausea, and vomiting.</span></p></div><div><h3>Conclusion</h3><p>In real-world clinical setting, TAS-102 showed consistent clinical efficacy and manageable safety with previous prospective clinical studies. Compared with monotherapy and TAS-102 plus ICIs, TAS-102 plus bevacizumab demonstrated better clinical efficacy for metastatic colorectal cancer.</p></div>","PeriodicalId":10373,"journal":{"name":"Clinical colorectal cancer","volume":"22 1","pages":"Pages 76-84"},"PeriodicalIF":3.4,"publicationDate":"2023-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9153556","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}