Clinical colorectal cancer最新文献

{"title":"Immunotherapy Rechallenge After Checkpoint Inhibitor Induced Hemophagocytic Lymphohistiocytosis: A Case Report and Literature Review","authors":"Dorien Geusens ,&nbsp;Daan Dierickx ,&nbsp;Saskia Carton ,&nbsp;Eric Van Cutsem ,&nbsp;Jeroen Dekervel","doi":"10.1016/j.clcc.2024.01.005","DOIUrl":"10.1016/j.clcc.2024.01.005","url":null,"abstract":"<div><p></p><ul><li><span>•</span><span><p>As there are increasingly more indications for immune checkpoint inhibitors (ICI), immune related adverse events will also become more prevalent. ICI induced haemophagocytic lymphohistiocytosis (HLH) has been described in case reports and pharmacovigilance database reviews. Literature regarding rechallenge of ICI after resolution of HLH is limited to a few cases.</p></span></li><li><span>•</span><span><p>With this case report, we want to highlight the need for early diagnosis and treatment. We also showed that ICI may be rechallenged safely, provided close monitoring and discussion with the patient.</p></span></li><li><span>•</span><span><p>This article might impact on clinical practice by increasing awareness about ICI induced HLH and contributing to the body of literature regarding this topic.</p></span></li></ul></div>","PeriodicalId":10373,"journal":{"name":"Clinical colorectal cancer","volume":"23 2","pages":"Pages 194-197"},"PeriodicalIF":3.4,"publicationDate":"2024-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139954084","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":"Plasma Angiogenic Factors as Predictors of the Efficacy of Second-line Chemotherapy Combined with Angiogenesis Inhibitors in Metastatic Colorectal Cancer: Results From the GI-SCREEN CRC-Ukit Study","authors":"Satoshi Yuki ,&nbsp;Kentaro Yamazaki ,&nbsp;Yu Sunakawa ,&nbsp;Hiroya Taniguchi ,&nbsp;Hideaki Bando ,&nbsp;Manabu Shiozawa ,&nbsp;Tomohiro Nishina ,&nbsp;Hisateru Yasui ,&nbsp;Akiyoshi Kanazawa ,&nbsp;Koji Ando ,&nbsp;Yosuke Horita ,&nbsp;Masahiro Goto ,&nbsp;Naohiro Okano ,&nbsp;Toshikazu Moriwaki ,&nbsp;Taroh Satoh ,&nbsp;Akihito Tsuji ,&nbsp;Kaname Yamashita ,&nbsp;Chiharu Asano ,&nbsp;Yukiko Abe ,&nbsp;Shogo Nomura ,&nbsp;Takayuki Yoshino","doi":"10.1016/j.clcc.2024.01.003","DOIUrl":"10.1016/j.clcc.2024.01.003","url":null,"abstract":"<div><h3>Background</h3><p>The significance of angiogenic factors as predictors of second-line (2L) chemotherapy efficacy when combined with angiogenesis inhibitors for metastatic colorectal cancer (mCRC) remains unestablished.</p></div><div><h3>Patients and Methods</h3><p>In this multicenter prospective observational study, 17 angiogenic factors were analyzed in plasma samples collected at pretreatment and progression stages using a Luminex multiplex assay. Patients who received chemotherapy plus bevacizumab (BEV group), FOLFIRI plus ramucirumab (RAM group), or FOLFIRI plus aflibercept (AFL group) as the 2L treatment were included. Interactions between pretreatment and treatment groups for progression-free survival (PFS), overall survival (OS), and response rate (RR) were assessed using the propensity-score weighted Cox proportional hazards model.</p></div><div><h3>Results</h3><p>From February 2018 to September 2020, 283 patients were analyzed in the 2L cohort. A strong interaction was observed for PFS between BEV and RAM with HGF, sNeuropilin-1, sVEGFR-1, and sVEGFR-3. Interactions for RR between the BEV and RAM groups were observed for sNeuropilin-1 and sVEGFR-1. Contrarily, OS, PlGF, sVEGFR-1, and sVEGFR-3 differentiated the treatment effect between BEV and AFL. Plasma samples were evaluable for dynamic analysis in 203 patients. At progression, VEGF-A levels significantly decreased in the BEV group and increased in the RAM and AFL groups.</p></div><div><h3>Conclusion</h3><p>The pretreatment plasma sVEGFR-1 and sVEGFR-3 levels could be predictive biomarkers for distinguishing BEV and RAM when combined with chemotherapy in 2L mCRC treatment. Based on the VEGF-A dynamics at progression, selecting RAM or AFL for patients with significantly elevated VEGF-A levels may be a 2L treatment strategy, with BEV considered for the third-line treatment.</p></div><div><h3>Clinical Trial Number</h3><p>UMIN000028616</p></div>","PeriodicalId":10373,"journal":{"name":"Clinical colorectal cancer","volume":"23 2","pages":"Pages 147-159.e7"},"PeriodicalIF":3.4,"publicationDate":"2024-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S1533002824000033/pdfft?md5=42c498ff6df05eb39c05ab54702a895e&pid=1-s2.0-S1533002824000033-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139506472","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":"Safety and Efficacy of Encorafenib, Binimetinib, and Cetuximab for BRAFV600E-Mutant Metastatic Colorectal Cancer: Results of the Japanese Expanded Access Program","authors":"Daisuke Kotani ,&nbsp;Atsuo Takashima ,&nbsp;Takeshi Kato ,&nbsp;Taroh Satoh ,&nbsp;Toshiki Masuishi ,&nbsp;Yoshito Komatsu ,&nbsp;Manabu Shiozawa ,&nbsp;Taito Esaki ,&nbsp;Naoki Izawa ,&nbsp;Shinji Takeuchi ,&nbsp;Hideaki Bando ,&nbsp;Satoru Iwasa ,&nbsp;Hiroko Hasegawa ,&nbsp;Toshifumi Yamaguchi ,&nbsp;Hiroya Taniguchi ,&nbsp;Yasunori Ushida ,&nbsp;Toshiya Oizaki ,&nbsp;Chiaki Inoue ,&nbsp;Takayuki Yoshino","doi":"10.1016/j.clcc.2024.02.002","DOIUrl":"10.1016/j.clcc.2024.02.002","url":null,"abstract":"<div><h3>Background</h3><p>The phase 3 BEACON CRC study demonstrated the survival benefits of encorafenib and cetuximab, with or without binimetinib (the BEACON triplet or doublet regimen), for <em>BRAF</em>^V600E-mutant metastatic colorectal cancer (mCRC). This expanded access program (EAP) and subsequent follow-up study assessed the efficacy and safety of the BEACON triplet regimen in Japanese patients with <em>BRAF</em>^V600E-mutant mCRC.</p></div><div><h3>Materials and Methods</h3><p>The EAP was an open-label, single-arm study including Japanese patients with <em>BRAF</em>^V600E-mutant mCRC whose disease progressed after 1 to 2 prior regimens. The patients received the BEACON triplet regimen with 28-day cycles. The subsequent follow-up study assessed the survival outcomes following EAP completion. Safety was assessed only during the EAP.</p></div><div><h3>Results</h3><p>Among the 86 enrolled patients, 81 received the BEACON triplet regimen. The objective response rate and median progression-free survival were 27.6% (95% confidence interval [CI], 18.0%-39.1%) and 5.26 (95% CI, 4.14-5.52) months, respectively. Grade 3 to 4 adverse events and treatment-related adverse events occurred in 43.2% and 28.4% of patients, respectively. No new safety signals were observed during the EAP. Among 58 patients with confirmed survival at EAP completion, 57 were included in the follow-up study. With a median observation period of 9.17 months through the EAP and follow-up study, the median overall survival was 10.38 (95% CI, 9.00-16.16) months.</p></div><div><h3>Conclusion</h3><p>The efficacy and safety of the BEACON triplet regimen in Japanese patients with <em>BRAF</em>^V600E-mutant mCRC were consistent with those reported in the BEACON CRC trial, supporting its use as a standard treatment for pretreated patients with <em>BRAF</em>^V600E-mutant mCRC.</p></div>","PeriodicalId":10373,"journal":{"name":"Clinical colorectal cancer","volume":"23 2","pages":"Pages 174-182.e6"},"PeriodicalIF":3.4,"publicationDate":"2024-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S1533002824000227/pdfft?md5=5027cd316a694fe6cd523116d4ee677e&pid=1-s2.0-S1533002824000227-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140149484","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":"The Effect of (Chemo)Radiotherapy on Enlarged Lateral Lymph Nodes in Patients With Locally Advanced Rectal Cancer","authors":"Charlène J. van der Zijden ,&nbsp;Hermien W.H. Schreurs ,&nbsp;Sjoerd van den Hoek ,&nbsp;Anne M. van Geel ,&nbsp;Jan Willem T. Dekker ,&nbsp;Daphne Roos","doi":"10.1016/j.clcc.2024.02.003","DOIUrl":"10.1016/j.clcc.2024.02.003","url":null,"abstract":"<div><h3>Background</h3><p>Standard of care for most patients with locally advanced rectal cancer in The Netherlands consists of neoadjuvant chemoradiotherapy (nCRT) followed by resection. Enlarged lateral lymph nodes (LLNs), especially in the iliac compartment, appears to be associated with an increased risk of local recurrence. Little is known about the risk of local recurrence after nCRT.</p></div><div><h3>Materials and Methods</h3><p>This study included patients with locally advanced rectal cancer and enlarged LLNs on pretreatment MRI-scan located in the internal iliac, obturator, external iliac, or common iliac compartment. Patients were treated with nCRT and response to therapy was evaluated with MRI-scan. The primary endpoint was local lateral recurrence after nCRT. Secondary endpoints included overall survival and postoperative complications.</p></div><div><h3>Results</h3><p>Out of 260 patients treated for rectal cancer, a total of 46 patients with enlarged LLNs (18% of all patients) were included between 2012 and 2019 in 2 Dutch hospitals. No patients had lateral lymph node recurrence (LLNR) after nCRT. Only 1 patient had local recurrence of rectal cancer after radical resection during a median follow up of 3 years. Disseminated disease was seen in 12 patients and 9 patients died during follow-up, which result in an overall survival rate of 80.4%. Postoperative complications were seen in 41% of patients. There was no 90-days postoperative mortality.</p></div><div><h3>Conclusion</h3><p>Enlarged LLNs are rare after nCRT and no LLNR was found after nCRT in our study population. This could suggest that nCRT only with or without an extra radiotherapeutic boost on enlarged LLNs already reduces the risk of LLNR.</p></div>","PeriodicalId":10373,"journal":{"name":"Clinical colorectal cancer","volume":"23 2","pages":"Pages 128-134.e1"},"PeriodicalIF":3.4,"publicationDate":"2024-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140797569","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":"Appropriate Relevancy and Reliability of Real-World Data for the Utilization of Regulatory Submission","authors":"Hideaki Bando ,&nbsp;Toshihiro Misumi ,&nbsp;Yasutoshi Sakamoto ,&nbsp;Yuriko Takeda ,&nbsp;Yoshiaki Nakamura ,&nbsp;Kazuya Mizuguchi ,&nbsp;Yoshihiro Aoyagi ,&nbsp;Izumi Miki ,&nbsp;Tomohiro Kuroda ,&nbsp;Ryu Kasai ,&nbsp;Takuya Suzuki ,&nbsp;Takayuki Yoshino ,&nbsp;Atsushi Ohtsu","doi":"10.1016/j.clcc.2024.04.001","DOIUrl":"10.1016/j.clcc.2024.04.001","url":null,"abstract":"<div><p>The extraction of data that contribute to regulatory approval from real-world data (RWD) is difficult because of the lack of a standardized data format and extraction methodology. Additionally, when real-world evidence (RWE) is used as an external control group, the similarity between internal and external control data is not evaluated. To investigate the data extraction methodology for the external control data of rare molecular subtypes, we have initiated the “REALISE” study. In this study, we aim to elucidate the “relevance” and “reliability” of RWD/RWE necessary for regulatory approval. As most databases are not designed for regulatory use in the creation phase, we will investigate retrospective methodologies to ensure RWD/RWE reliability. This study will compare the “relevance” and “reliability” of the ARCAD global database, SCRUM-Japan Registry, SCRUM-Japan observational study, and Flatiron Health RWD, and statistically analyze the differences and similarities among the four databases. We will also examine the methodology for extracting sufficiently relevant data from the SCRUM-Japan observational study. Additionally, if the reliability of the RWD/RWE does not reach the required level for regulatory approval, we will examine the methodologies to ensure the “reliability” of the SCRUM-Japan observational study for regulatory approval. The obtained results will be submitted to the “Consultation for Development of Registry” in the Pharmaceuticals and Medical Devices Agency, and we will discuss the standard methodology. The procedures and findings identified in the REALISE study will be organized from the perspectives of “database construction,” “data analysis,” and “outcome evaluation” and will be issued as “the draft guidelines.”</p></div>","PeriodicalId":10373,"journal":{"name":"Clinical colorectal cancer","volume":"23 2","pages":"Pages 111-117"},"PeriodicalIF":3.4,"publicationDate":"2024-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140764579","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":"Explanatory Role of Conversion Surgery as a Mediator of the Mortality Risk Difference Between Patients With Unresectable Metastatic Colorectal Cancer Treated With First-Line Anti-EGFR Agents Versus Bevacizumab","authors":"Chien-Chou Su ,&nbsp;Yi-Chia Su ,&nbsp;Chih-Chien Wu ,&nbsp;Pei-Ting Lee","doi":"10.1016/j.clcc.2024.05.008","DOIUrl":"10.1016/j.clcc.2024.05.008","url":null,"abstract":"<div><h3>Introduction</h3><div>Bevacizumab<span> and antiepidermal growth factor receptor-blocking (anti-EGFR) agents plus chemotherapy are first-line therapies for metastatic colorectal cancer<span> (mCRC). Conversion surgery may improve outcomes; however, the extent to which it explains the difference in mortality rates among treatments is unclear. Herein, we aimed to assess the effects of conversion surgery on survival outcomes of patients with unresectable mCRC treated with bevacizumab and anti-EGFR agents.</span></span></div></div><div><h3>Materials and methods</h3><div>This retrospective cohort study<span> included patients with mCRC treated with bevacizumab and anti-EGFR agents as first-line therapy. We estimated the direct and indirect effects of treatments by comparing the mortality risk associated with targeted therapy type. Hazard ratios (HR) and the corresponding confidence intervals (CI) were estimated. Mediation analysis was used to estimate hazard ratio differences, and the proportion mediated.</span></div></div><div><h3>Results</h3><div>A total of 5,106 patients were included. The natural indirect effect of conversion surgery reduced mortality risk (HR: 0.95; 95% CI, 0.93-0.97), with a mediated proportion of 42% after propensity score adjustment. In subgroup analyses, <span><span>KRAS</span></span><span> wild-type (HR: 0.94; 95% CI: 0.91-0.97), left tumor sidedness (HR: 0.94; 95% CI, 0.91-0.96), and liver resection (HR: 0.95; 95% CI, 0.93-0.98) were associated with reduced risks of mortality. The controlled and total direct effects of targeted therapy were associated with reduced mortality risk in the anti-EGFR-treated group compared to those in the bevacizumab-treated group; however, this effect was not statistically significant.</span></div></div><div><h3>Conclusion</h3><div>Conversion surgery may account for the difference in survival outcomes between users of the anti-EGFR agents and bevacizumab.</div></div>","PeriodicalId":10373,"journal":{"name":"Clinical colorectal cancer","volume":"23 4","pages":"Pages 364-371"},"PeriodicalIF":3.3,"publicationDate":"2024-05-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141328232","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":"Survival Outcomes in Patients with Monobloc-Resected Stage IIC (pT4bN0) Colon Cancer: A Retrospective Observational Cohort Study","authors":"Juliette Logeart ,&nbsp;Thomas Samaille ,&nbsp;Antoine Falcoz ,&nbsp;Magali Svrcek ,&nbsp;Olivier Dubreuil ,&nbsp;Dewi Vernerey ,&nbsp;Romain Cohen ,&nbsp;Pascale Cervera ,&nbsp;Alain Valverde ,&nbsp;Yann Parc ,&nbsp;Thierry André","doi":"10.1016/j.clcc.2024.05.005","DOIUrl":"10.1016/j.clcc.2024.05.005","url":null,"abstract":"<div><h3>Background</h3><div>Stage II colon cancer<span> (CC) exhibits considerable prognostic heterogeneous. Our objective was to assess survival but also the prognosis impact of microsatellite instability (MSI) in patients with stage IIC (T4bN0M0) CC.</span></div></div><div><h3>Patients and Methods</h3><div>We conducted a retrospective observational study including all patients who had primary stage IIC CC resection between 2010 and 2020 in 2 expert centers. The primary endpoint was overall survival (OS) and disease-free survival (DFS) and time-to-relapse (TTR) were secondary endpoints.</div></div><div><h3>Results</h3><div><span><span>Sixty-six patients, median age of 74 years [30-95], were included, with 37.9% presenting MSI (n = 25). Organ invasion involved the last ileal loop (n = 17), another colonic segment (n = 15), omentum (n = 13), visceral </span>peritoneum<span> (n = 13), and the bladder (n = 4). Surgical quality criteria showed complete monobloc resection in all patients and 93.9% R0 resection. After a median follow-up of 5 years [3.5-6.6], the entire population showed a 5-year OS of 65.2% [53.0-80.3] and 5-year DFS of 53.5% [41.1-69.6], with 18.9% [6.8-29.4] experiencing relapses at 5 years. The MSI phenotype correlated with improved 5-year OS (75.5% [56.5-100] vs. 59.5% [44.9-79.0], HR 0.41 [0.17-0.99]; </span></span><em>P</em><span><span> = .04), but DFS and TTR did not differ. Adjuvant chemotherapy was administered to 34.9% of patients. </span>Univariate analysis identified age &gt; 65 years, MSI status, and the number of nodes as factors associated with OS.</span></div></div><div><h3>Conclusion</h3><div>These data underline, in relation to a low rate of relapse, the lack of consensus regarding the appropriate indication for adjuvant chemotherapy in this high-risk stage II population.</div></div>","PeriodicalId":10373,"journal":{"name":"Clinical colorectal cancer","volume":"23 4","pages":"Pages 346-353.e1"},"PeriodicalIF":3.3,"publicationDate":"2024-05-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141144365","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":"Peritoneal Carcinomatosis in Colorectal Cancer: Review and Update of Current Clinical Data","authors":"S. Blaj ,&nbsp;H. Leebmann ,&nbsp;M. Babucke ,&nbsp;M. Acs ,&nbsp;P. Piso","doi":"10.1016/j.clcc.2024.05.007","DOIUrl":"10.1016/j.clcc.2024.05.007","url":null,"abstract":"<div><div><span>The peritoneal metastasized colorectal cancer<span> (pmCRC) represents a serious health problem worldwide with a special emphasis in the developed countries. Several guidelines recognize the role of multimodal therapy consisting of cytoreductive surgery (CRS) and hyperthermic </span></span>intraperitoneal chemotherapy<span> (HIPEC) in the treatment of pmCRC. New data suggests that some other factors, eg, tumor biology, immune profile, neoadjuvant chemotherapy may play a predictive role for the oncological outcome of these patients.</span></div></div>","PeriodicalId":10373,"journal":{"name":"Clinical colorectal cancer","volume":"23 4","pages":"Pages 309-317"},"PeriodicalIF":3.3,"publicationDate":"2024-05-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141145619","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":"VIC Regimen (Vemurafenib/Irinotecan/Cetuximab) Versus Bevacizumab Plus Chemotherapy as First-Line Treatment for BRAF V600E-Mutated Unresectable or Metastatic Colorectal Cancer in Asian Patients: A Prospective Cohort Study","authors":"Yijiao Chen ,&nbsp;Dexiang Zhu ,&nbsp;Yiyi Yu ,&nbsp;Wenju Chang ,&nbsp;Lechi Ye ,&nbsp;Qingyang Feng ,&nbsp;Pingping Xu ,&nbsp;Miao Chen ,&nbsp;Meiling Ji ,&nbsp;Ye Wei ,&nbsp;Tianshu Liu ,&nbsp;Jianmin Xu","doi":"10.1016/j.clcc.2024.05.006","DOIUrl":"10.1016/j.clcc.2024.05.006","url":null,"abstract":"<div><h3>Background</h3><div>Colorectal cancers (CRC) with BRAF V600E mutation exhibit limited chemotherapy response and a poor prognosis. Safety and efficacy of the VIC (Vemurafenib/Irinotecan/Cetuximab) regimen in the first-line setting for patients with BRAF V600E-mutated CRC remain undetermined.</div></div><div><h3>Methods</h3><div><span><span>In the prospective cohort study, the untreated, BRAF V600E-mutated, unresectable or </span>metastatic CRC patients were enrolled. The VIC regimen and </span>bevacizumab<span> plus chemotherapy were compared in the first-line setting. The objective response rate (ORR), disease control rate (DCR), conversion resection rate, progression-free survival (PFS), and overall survival (OS) were evaluated.</span></div></div><div><h3>Results</h3><div>In the intent-to-treat analysis, 38 patients received VIC regimen and 40 received bevacizumab plus chemotherapy. The ORR and DCR in the VIC group were significantly higher than in the bevacizumab-therapy group (ORR: 63.2% vs. 37.5%, <em>P</em> = .025; DCR: 94.7% vs. 75.0%, <em>P</em> = .019). The VIC regimen significantly outperformed bevacizumab plus chemotherapy in both PFS (11.9 vs. 7.7 months; hazard ratio [HR] = 0.51, 95% CI, 0.30-0.87; <em>P</em> = .010) and OS (25.3 vs. 14.6 months; HR = 0.43, 95% CI, 0.22-0.82; <em>P</em><span><span> = .011). In the VIC group, the conversion resection rate for liver metastases was 34.8% (8 of 23 patients), and for unresectable local CRC it was 54.5% (6 of 11 patients). The </span>adverse events rates of Grade 3 to 4 were 34.2% and 32.5% for the VIC regimen and bevacizumab plus chemotherapy respectively.</span></div></div><div><h3>Conclusions</h3><div>Among Asian patients with BRAF V600E-mutated CRC, the VIC regimen showed favorable outcomes compared to bevacizumab plus chemotherapy in terms of tumor response and oncological survival, with a tolerable and manageable toxicity profile in the first-line setting.</div></div>","PeriodicalId":10373,"journal":{"name":"Clinical colorectal cancer","volume":"23 4","pages":"Pages 354-363.e4"},"PeriodicalIF":3.3,"publicationDate":"2024-05-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141130844","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":"A Phase 1 Study of Cabozantinib and Trifluridine/Tipiracil in Metastatic Colorectal Adenocarcinoma","authors":"Farshid Dayyani ,&nbsp;Jasmine Balangue ,&nbsp;Jennifer Valerin ,&nbsp;Matthew J. Keating ,&nbsp;Jason A. Zell ,&nbsp;Thomas H. Taylor ,&nbsp;May T. Cho","doi":"10.1016/j.clcc.2023.11.001","DOIUrl":"10.1016/j.clcc.2023.11.001","url":null,"abstract":"<div><h3>Introduction</h3><p><span>This study determined the safety and recommended phase 2 dose (RP2D) of the multikinase inhibitor cabozantinib in combination with trifluridine/tipiracil (FTD/TPI) in refractory metastatic </span>colorectal carcinoma (mCRC).</p></div><div><h3>Patients and Methods</h3><p>Single institution investigator-initiated phase 1 study using 3+3 design. Eligible mCRC patients had received prior standard regimens. Cabozantinib was given orally (p.o.) at 20 mg (dose level [DL] 0) or 40 mg (DL 1) daily on days 1-28, and FTD/TPI p.o. at 35 mg/m² on days 1-5 and 8-12 every 28 days. Prophylactic growth-factor support was allowed.</p></div><div><h3>Results</h3><p>Fifteen patients were enrolled. Median age 56 years (31-80), male (12/15), ECOG<span><span><span> 0/1 = 9/6. Three patients were treated at DL 0 and another nine were treated at DL 1, none exhibiting a DLT. Most common any grade (G) treatment related adverse events (TRAE) were diarrhea (50%), nausea (42%), neutropenia (42%), fatigue (33%), and rash (25%). G3-4 TRAE were neutropenia (25%) and thrombocytopenia, </span>hypokalemia, and weight loss (each 8%). No serious TRAE or G5 were reported. The RP2D was determined to be DL 1. Median </span>PFS was 3.8 months (95% CI 1.9-6.8) and disease control rate was 86.7%.</span></p></div><div><h3>Conclusion</h3><p>The combination of cabozantinib and FTD/TPI is feasible and tolerable at standard doses with the use of growth factors and showed encouraging clinical activity in refractory mCRC.</p></div><div><h3>ClinicalTrials.Gov</h3><p>NCT04868773.</p></div>","PeriodicalId":10373,"journal":{"name":"Clinical colorectal cancer","volume":"23 1","pages":"Pages 67-72"},"PeriodicalIF":3.4,"publicationDate":"2024-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138525565","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}