Clinical colorectal cancer最新文献

{"title":"Treatment of Metastatic Biliary Cancers With Irinotecan and 5-Fluorouracil Based Chemotherapy After Platinum/Gemcitabine Progression: A Systematic Review and Meta-Analysis","authors":"Ioannis A. Voutsadakis ,&nbsp;Stefania Kokkali ,&nbsp;Antonia Digklia","doi":"10.1016/j.clcc.2024.05.009","DOIUrl":"10.1016/j.clcc.2024.05.009","url":null,"abstract":"<div><h3>Background</h3><div>Biliary tract carcinomas<span><span> are cancers that, despite a lower prevalence compared with other gastrointestinal cancers, represent a significant </span>public health burden due to their aggressiveness. The metastatic stage of the disease is highly lethal and difficult to treat. Options of systemic therapies, especially beyond the first line are few and less well established.</span></div></div><div><h3>Methods</h3><div><span>We performed a systematic review<span><span> of literature databases to identify studies of the combination of irinotecan and 5-fluorouracil (5-FU) based chemotherapy as treatment of metastatic biliary tract carcinomas in second line, after first line treatment with platinum/gemcitabine chemotherapy. Both prospective and retrospective designs were admissible. A meta-analysis of identified studies to determine summary estimates for overall response rate (ORR), disease control rate (DCR), </span>progression free survival (PFS) and </span></span>overall survival (OS) was also performed.</div></div><div><h3>Results</h3><div>The search was performed in PubMed/Medline and in Embase databases and identified a total of 339 articles. Manual review resulted in 8 articles that were eligible for inclusion in the meta-analysis. Second line irinotecan/5-FU based combinations produced an ORR of 9.1% (95% CI, 5.5%-12.6%) and DCR of 43.3% (95% CI, 15.8%-70.8%). Summary PFS and OS were 2.7 months (95% CI, 2.3-3.1 months) and 6.8 months (95% CI, 5.6-8.0 months), respectively. Treatments appeared to be feasible with adverse effect profiles as expected from the combination.</div></div><div><h3>Conclusion</h3><div>A moderate activity of second line irinotecan/5-FU based chemotherapy was observed in this meta-analysis. The combination is an option for patients progressing on platinum/gemcitabine chemotherapy, who maintain a sufficient general status to receive active therapy. This combination may also serve as the control arm of second line trials with new targeted agents.</div></div>","PeriodicalId":10373,"journal":{"name":"Clinical colorectal cancer","volume":"23 4","pages":"Pages 318-325.e1"},"PeriodicalIF":3.3,"publicationDate":"2024-06-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141278014","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":"Pembrolizumab Plus mFOLFOX7 or FOLFIRI for Microsatellite Stable/Mismatch Repair-Proficient Metastatic Colorectal Cancer: KEYNOTE-651 Cohorts B and D","authors":"Richard Kim ,&nbsp;Mustapha Tehfe ,&nbsp;Petr Kavan ,&nbsp;Jorge Chaves ,&nbsp;Jeremy S. Kortmansky ,&nbsp;Eric X. Chen ,&nbsp;Christopher H. Lieu ,&nbsp;Lucas Wong ,&nbsp;Marwan Fakih ,&nbsp;Kristen Spencer ,&nbsp;Qing Zhao ,&nbsp;Raluca Predoiu ,&nbsp;Chenxiang Li ,&nbsp;Pierre Leconte ,&nbsp;David Adelberg ,&nbsp;E. Gabriela Chiorean","doi":"10.1016/j.clcc.2024.03.001","DOIUrl":"10.1016/j.clcc.2024.03.001","url":null,"abstract":"<div><h3>Background</h3><p>The phase 1b KEYNOTE-651 study evaluated pembrolizumab plus chemotherapy in microsatellite stable or mismatch repair-proficient metastatic colorectal cancer.</p></div><div><h3>Patients and Methods</h3><p>Patients with microsatellite stable or mismatch repair-proficient metastatic colorectal cancer received pembrolizumab 200 mg every 3 weeks plus 5-fluorouracil, leucovorin, oxaliplatin (previously untreated; cohort B) or 5-fluorouracil, leucovorin, irinotecan (previously treated with fluoropyrimidine plus oxaliplatin; cohort D) every 2 weeks. Primary end point was safety; investigator-assessed objective response rate per RECIST v1.1 was secondary and biomarker analysis was exploratory.</p></div><div><h3>Results</h3><p>Thirty-one patients were enrolled in cohort B and 32 in cohort D; median follow-up was 30.2 and 33.5 months, respectively. One dose-limiting toxicity (grade 3 small intestine obstruction) occurred in cohort D. In cohort B, grade 3 or 4 treatment-related adverse events (AEs) occurred in 18 patients (58%), most commonly neutropenia and decreased neutrophil count (n = 5 each). In cohort D, grade 3 or 4 treatment-related AEs occurred in 17 patients (53%), most commonly neutropenia (n = 7). No grade 5 treatment-related AEs occurred. Objective response rate was 61% in cohort B (<em>KRAS</em> wildtype: 71%; <em>KRAS</em> mutant: 53%) and 25% in cohort D (<em>KRAS</em> wildtype: 47%; <em>KRAS</em> mutant: 6%). In both cohorts, PD-L1 combined positive score and T-cell-inflamed gene expression profiles were higher and HER2 expression was lower in responders than nonresponders. No association between tumor mutational burden and response was observed.</p></div><div><h3>Conclusion</h3><p>Pembrolizumab plus 5-fluorouracil, leucovorin, oxaliplatin/5-fluorouracil, leucovorin, irinotecan demonstrated an acceptable AE profile. Efficacy data appeared comparable with current standard of care (including by <em>KRAS</em> mutation status). Biomarker analyses were hypothesis-generating, warranting further exploration.</p></div><div><h3>ClinicalTrials.gov Identifier</h3><p>ClinicalTrials.gov; NCT03374254</p></div>","PeriodicalId":10373,"journal":{"name":"Clinical colorectal cancer","volume":"23 2","pages":"Pages 118-127.e6"},"PeriodicalIF":3.4,"publicationDate":"2024-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140613984","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":"Consideration of Metastasis-Directed Therapy for Patients With Metastatic Colorectal Cancer: Expert Survey and Systematic Review","authors":"Eric D. Miller ,&nbsp;Brett G. Klamer ,&nbsp;Jordan M. Cloyd ,&nbsp;Timothy M. Pawlik ,&nbsp;Terence M. Williams ,&nbsp;Kathryn E. Hitchcock ,&nbsp;Paul B. Romesser ,&nbsp;Harvey J. Mamon ,&nbsp;Kimmie Ng ,&nbsp;Sepideh Gholami ,&nbsp;George J. Chang ,&nbsp;Christopher J. Anker","doi":"10.1016/j.clcc.2024.01.004","DOIUrl":"10.1016/j.clcc.2024.01.004","url":null,"abstract":"<div><h3>Background</h3><p>A survey of medical oncologists (MOs), radiation oncologists (ROs), and surgical oncologists (SOs) who are experts in the management of patients with metastatic colorectal cancer (mCRC) was conducted to identify factors used to consider metastasis-directed therapy (MDT).</p></div><div><h3>Materials and Methods</h3><p>An online survey to assess clinical factors when weighing MDT in patients with mCRC was developed based on systematic review of the literature and integrated with clinical vignettes. Supporting evidence from the systematic review was included to aid in answering questions.</p></div><div><h3>Results</h3><p>Among 75 experts on mCRC invited, 47 (response rate 62.7%) chose to participate including 16 MOs, 16 ROs, and 15 SOs. Most experts would not consider MDT in patients with 3 lesions in both the liver and lung regardless of distribution or timing of metastatic disease diagnosis (6 vs. 36 months after definitive treatment). Similarly, for patients with retroperitoneal lymph node and lung and liver involvement, most experts would not offer MDT regardless of timing of metastatic disease diagnosis. In general, SOs were willing to consider MDT in patients with more advanced disease, ROs were more willing to offer treatment regardless of metastatic site location, and MOs were the least likely to consider MDT.</p></div><div><h3>Conclusions</h3><p>Among experts caring for patients with mCRC, significant variation was noted among MOs, ROs, and SOs in the distribution and volume of metastatic disease for which MDT would be considered. This variability highlights differing opinions on management of these patients and underscores the need for well-designed prospective randomized trials to characterize the risks and potential benefits of MDT.</p></div>","PeriodicalId":10373,"journal":{"name":"Clinical colorectal cancer","volume":"23 2","pages":"Pages 160-173"},"PeriodicalIF":3.4,"publicationDate":"2024-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S1533002824000045/pdfft?md5=b73b78ab7b7a93a7f10dda6c37cb59c4&pid=1-s2.0-S1533002824000045-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139646133","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":"Pembrolizumab Plus Binimetinib With or Without Chemotherapy for MSS/pMMR Metastatic Colorectal Cancer: Outcomes From KEYNOTE-651 Cohorts A, C, and E","authors":"Eric X. Chen ,&nbsp;Petr Kavan ,&nbsp;Mustapha Tehfe ,&nbsp;Jeremy S. Kortmansky ,&nbsp;Michael B. Sawyer ,&nbsp;E. Gabriela Chiorean ,&nbsp;Christopher H. Lieu ,&nbsp;Blase Polite ,&nbsp;Lucas Wong ,&nbsp;Marwan Fakih ,&nbsp;Kristen Spencer ,&nbsp;Jorge Chaves ,&nbsp;Chenxiang Li ,&nbsp;Pierre Leconte ,&nbsp;David Adelberg ,&nbsp;Richard Kim","doi":"10.1016/j.clcc.2024.03.002","DOIUrl":"10.1016/j.clcc.2024.03.002","url":null,"abstract":"<div><h3>Background</h3><p>Cohorts A, C, and E of the phase Ib KEYNOTE-651 study evaluated pembrolizumab + binimetinib ± chemotherapy in microsatellite stable/mismatch repair-proficient metastatic colorectal cancer.</p></div><div><h3>Patients and Methods</h3><p>Patients received pembrolizumab 200 mg every 3 weeks plus binimetinib 30 mg twice daily alone (cohort A; previously treated with any chemotherapy) or with 5-fluorouracil, leucovorin, oxaliplatin (cohort C; previously untreated) or 5-fluorouracil, leucovorin, irinotecan (cohort E; previously treated with 1 line of therapy including fluoropyrimidine + oxaliplatin-based regimen) every 2 weeks. Binimetinib dose-escalation to 45 mg twice daily was planned in all cohorts using a modified toxicity probability interval design (target dose-limiting toxicity [DLT], 30%). The primary endpoint was safety; investigator-assessed objective response rate was secondary.</p></div><div><h3>Results</h3><p>In cohort A, 1/6 patients (17%) had DLTs with binimetinib 30 mg; none occurred in 14 patients with 45 mg. In cohort C, 3/9 patients (33%) had DLTs with binimetinib 30 mg; dose was not escalated to 45 mg. In cohort E, 1/5 patients (20%) had DLTs with binimetinib 30 mg; 5/10 patients (50%) had DLTs with 45 mg. Enrollment was stopped in cohort E binimetinib 45 mg and deescalated to 30 mg; 2/4 additional patients (50%) had DLTs with binimetinib 30 mg (total 3/9 [33%] had DLTs with binimetinib 30 mg). Objective response rate was 0% in cohort A, 9% in cohort C, and 15% in cohort E.</p></div><div><h3>Conclusion</h3><p>Per DLT criteria, binimetinib + pembrolizumab (cohort A) was tolerable, binimetinib + pembrolizumab + 5-fluorouracil, leucovorin, oxaliplatin (cohort C) did not qualify for binimetinib dose escalation to 45 mg, and binimetinib + pembrolizumab + 5-fluorouracil, leucovorin, irinotecan (cohort E) required binimetinib dose reduction from 45 to 30 mg. No new safety findings were observed across cohorts. There was no apparent additive efficacy when binimetinib + pembrolizumab was added to chemotherapy. Data did not support continued enrollment in cohorts C and E.</p></div>","PeriodicalId":10373,"journal":{"name":"Clinical colorectal cancer","volume":"23 2","pages":"Pages 183-193"},"PeriodicalIF":3.4,"publicationDate":"2024-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140614047","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":"Complete Obstruction, a Real Risk Factor: A Comprehensive Study on Obstruction in Stage IIA Colon Cancer With Propensity Score Matching Analysis","authors":"Soo Young Oh ,&nbsp;Chan Wook Kim ,&nbsp;Seonok Kim ,&nbsp;Min Hyun Kim ,&nbsp;Young Il Kim ,&nbsp;Jong Lyul Lee ,&nbsp;Yong Sik Yoon ,&nbsp;In Ja Park ,&nbsp;Seok-Byung Lim ,&nbsp;Chang Sik Yu","doi":"10.1016/j.clcc.2024.04.002","DOIUrl":"10.1016/j.clcc.2024.04.002","url":null,"abstract":"<div><h3>Microabstract</h3><p>This study evaluates the prognostic significance of obstructions in stage IIA colon cancer, distinguishing between partial and complete obstructions. It employs a retrospective review of 1914 patients with propensity score matching to analyze oncologic outcomes. Findings reveal complete obstruction as a significant risk factor for poorer outcomes, emphasizing the necessity for further research to refine treatment strategies, particularly regarding the efficacy of adjuvant chemotherapy across obstruction types.</p></div><div><h3>Background</h3><p>This study examined the prognostic impact of obstructions in stage IIA colon cancer. The analysis specifically differentiated partial and complete obstructions, analyzing their distinct influences of both on oncologic outcomes.</p></div><div><h3>Materials and Methods</h3><p>A retrospective review was conducted of stage IIA colon cancer cases with the presence of an obstruction. Patients were stratified by whether it was partial or complete based on the severity of obstruction. Propensity score matching was employed to control for confounders.</p></div><div><h3>Results</h3><p>Among 1914 consecutive patients diagnosed with stage IIA colon cancer, 758 patients (597 patients with partial obstruction, 161 patients with complete obstruction) exhibited obstruction, while 1156 patients had no obstruction. The median follow-up period was 126 months. Complete obstruction was associated with poorer disease-free survival (Hazard ratio (HR) = 1.785, <em>P</em> &lt; .001) and overall survival (HR = 1.853, <em>P</em> = .001). This trend persisted after propensity score matching, patients with complete obstruction showing a worsened disease-free survival (HR = 1.666, <em>P</em> = .028) and overall survival (HR = 1.732, <em>P</em> = .041). Adjuvant chemotherapy showed improved outcomes overall, but its efficacy varied across obstruction types.</p></div><div><h3>Conclusion</h3><p>Differentiating between complete and partial obstructions in stage IIA colon cancer is an important clinical distinction, as our findings suggest that complete obstruction is a significant risk factor for poorer oncologic outcomes. While adjuvant chemotherapy generally improves prognosis in stage IIA colon cancer, the correlation of obstruction type with its efficacy remains uncertain, necessitating further research to refine treatment strategies.</p></div>","PeriodicalId":10373,"journal":{"name":"Clinical colorectal cancer","volume":"23 2","pages":"Pages 135-146.e3"},"PeriodicalIF":3.4,"publicationDate":"2024-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140762548","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":"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}