ESMO Gastrointestinal Oncology最新文献

{"title":"BAYONET trial: staged combination with encorafenib, binimetinib, plus cetuximab following encorafenib plus cetuximab for BRAF V600E-mutant metastatic colorectal cancer","authors":"Y. Matsubara ,&nbsp;H. Bando ,&nbsp;D. Kotani ,&nbsp;Y. Kagawa ,&nbsp;K. Harada ,&nbsp;H. Osumi ,&nbsp;N. Izawa ,&nbsp;T. Kawakami ,&nbsp;S. Boku ,&nbsp;T. Matsumoto ,&nbsp;M. Wakabayashi ,&nbsp;T. Yoshino","doi":"10.1016/j.esmogo.2024.100066","DOIUrl":"https://doi.org/10.1016/j.esmogo.2024.100066","url":null,"abstract":"<div><h3>Background</h3><p>While the triplet combination of encorafenib (ENCO), binimetinib (BINI), plus cetuximab (CET) yielded a higher response rate compared with the doublet combination of ENCO plus CET, no significant survival benefits of the triplet combination were observed in patients with <em>BRAF</em> V600E-mutant metastatic colorectal cancer (mCRC), according to the BEACON CRC study. Although ENCO plus CET is the standard second-line therapy, poor prognoses are expected after disease progression.</p></div><div><h3>Trial design</h3><p>BAYONET is a single-arm multicenter phase II trial designed to evaluate the efficacy and safety of staged combination with ENCO, BINI, plus CET for patients with <em>BRAF</em> V600E-mutant mCRC refractory to ENCO plus CET. The main inclusion criteria are as follows: <em>RAS</em> wild-type/<em>BRAF</em> V600E-mutant mCRC; &lt;4 weeks from the last administration of previous ENCO or CET; no administration of other systemic therapy after refractoriness to ENCO plus CET; and complete response, partial response, or ≥4 months of stable disease in the previous ENCO plus CET. The primary endpoint of this trial is the 12-week progression-free survival rate. As a translational analysis, circulating tumor DNA for next-generation sequencing using Guardant360 is collected at two time points (before and after study treatment) to investigate potential mechanisms of resistance.</p></div>","PeriodicalId":100490,"journal":{"name":"ESMO Gastrointestinal Oncology","volume":"4 ","pages":"Article 100066"},"PeriodicalIF":0.0,"publicationDate":"2024-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S294981982400027X/pdfft?md5=b67d1599e4ccac70c939e9503027a495&pid=1-s2.0-S294981982400027X-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141243474","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Efficacy and safety of short-course radiotherapy versus total neoadjuvant therapy in older rectal cancer patients: a randomised pragmatic trial (SHAPERS)","authors":"R. Saúde-Conde ,&nbsp;T. Vandamme ,&nbsp;M. De Backer ,&nbsp;P. Martinive ,&nbsp;A. Covas ,&nbsp;A. Deleporte ,&nbsp;A. Dermine ,&nbsp;F. Forget ,&nbsp;K. Geboes ,&nbsp;Q. Gilliaux ,&nbsp;Y. Gokburun ,&nbsp;E. Gonne ,&nbsp;I. Joye ,&nbsp;S. Lecomte ,&nbsp;G. Liberale ,&nbsp;W. Lybaert ,&nbsp;L. Moretti ,&nbsp;L. Mortier ,&nbsp;S. Mupingu Mwanawa ,&nbsp;F. Puleo ,&nbsp;F. Sclafani","doi":"10.1016/j.esmogo.2024.100067","DOIUrl":"https://doi.org/10.1016/j.esmogo.2024.100067","url":null,"abstract":"<div><p>Although total neoadjuvant therapy (TNT) is a new standard of care for locally advanced rectal cancer (LARC), there are no data to confirm the safety and efficacy of this approach in older patients. SHAPERS is a multicentre, open-label, randomised pragmatic trial, aiming to assess whether neoadjuvant short-course radiotherapy (SCRT) is a better trade-off between safety and efficacy than TNT in LARC patients aged ≥70 years. Eligible patients are randomised in a 1 : 1 ratio to SCRT followed by surgery [or watch &amp; wait (w&amp;w)] ± adjuvant chemotherapy or TNT (either SCRT followed by 12-18 weeks of chemotherapy, or long-course chemoradiotherapy followed or preceded by 16 weeks of chemotherapy, based on the investigator’s choice) followed by surgery (or w&amp;w). The primary endpoint is the net treatment benefit, a multicomponent measure of treatment effect based on generalised pairwise comparisons, and defined by four prioritised outcome measures: (i) overall survival at 3 years; (ii) progression-free survival at 3 years; (iii) increased-grade peripheral sensory neuropathy at 3 years; (iv) grade ≥3 toxicities during treatment. The study sample size includes 230 eligible patients, to be recruited at 15-20 centres in Belgium. The trial is registered with <span>ClinicalTrials.gov</span><svg><path></path></svg> (NCT06052332).</p></div>","PeriodicalId":100490,"journal":{"name":"ESMO Gastrointestinal Oncology","volume":"4 ","pages":"Article 100067"},"PeriodicalIF":0.0,"publicationDate":"2024-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2949819824000281/pdfft?md5=94ffabe32898c394b2577b266ed40d19&pid=1-s2.0-S2949819824000281-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141264006","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Clinical impact of circulating tumor DNA to track minimal residual disease in colorectal cancer patients. Hopes and limitations","authors":"C. Soueidy ,&nbsp;A. Zaanan ,&nbsp;M. Gelli ,&nbsp;E. Moati ,&nbsp;C. Gallois ,&nbsp;V. Taly ,&nbsp;P. Laurent-Puig ,&nbsp;L. Benhaim ,&nbsp;J. Taieb","doi":"10.1016/j.esmogo.2024.100068","DOIUrl":"https://doi.org/10.1016/j.esmogo.2024.100068","url":null,"abstract":"<div><p>Circulating tumor DNA (ctDNA) has been studied as a non-invasive tool for disease monitoring in different cancer types. Despite advances in colorectal cancer (CRC) management, it remains a leading cause of mortality and there is an unmet need for new biomarkers to guide therapeutic approaches and improve patient’s outcome after surgical resection of the primary tumor or its metastatic sites. This review summarizes the different clinical results and ongoing studies on the performances of ctDNA as a prognostic marker for disease recurrence, both in non-metastatic patients with resection of the primary tumor and in those with full resection of metastatic disease.</p></div>","PeriodicalId":100490,"journal":{"name":"ESMO Gastrointestinal Oncology","volume":"4 ","pages":"Article 100068"},"PeriodicalIF":0.0,"publicationDate":"2024-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2949819824000293/pdfft?md5=e9e60d244502fe23cae10f54db5ff97c&pid=1-s2.0-S2949819824000293-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141243475","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Sidedness and addition of chemotherapy associated with treatment outcomes of regorafenib for metastatic colorectal cancer: a population-wide cohort study","authors":"T.-C. Wu ,&nbsp;Y.-H. Liang ,&nbsp;K.-H. Chen ,&nbsp;Y.-Y. Shao","doi":"10.1016/j.esmogo.2024.100052","DOIUrl":"https://doi.org/10.1016/j.esmogo.2024.100052","url":null,"abstract":"<div><h3>Background</h3><p>Regorafenib is a salvage option for metastatic colorectal cancer (mCRC). Understanding the prognostic factors for mCRC patients undergoing regorafenib treatment can help optimize therapeutic strategies.</p></div><div><h3>Materials and methods</h3><p>We searched Taiwan’s National Health Insurance database for patients who began regorafenib treatment for mCRC between 1 September 2015 and 31 December 2018. Taiwan’s National Death Registry and the Taiwan Cancer Registry were examined for data on survival and clinicopathological variables, respectively.</p></div><div><h3>Results</h3><p>In total, 3643 patients were included in the analysis. The median time to treatment discontinuation (TTD) was 2.3 months, and the median overall survival (OS) was 7.2 months. Compared with the patients with a right-sided tumor, those with a left-sided primary tumor exhibited a significantly longer TTD (2.4 versus 2.1 months, <em>P</em> &lt; 0.001) and OS (7.6 versus 6.1 months, <em>P</em> &lt; 0.001). The patients who received chemotherapy with regorafenib also exhibited a longer TTD (2.6 versus 2.2 months, <em>P</em> &lt; 0.001) and OS (8.3 versus 6.7 months, <em>P</em> &lt; 0.001) than did the patients who did not. In multivariate analysis, left-sidedness and chemotherapy addition were confirmed as predictors of longer TTD and OS. Because of the interaction between sidedness and <em>KRAS</em> mutation, we established separate Cox models and identified that left-sidedness was an independent predictor of longer TTD and OS for <em>KRAS</em> wild-type tumors but not for <em>KRAS</em>-mutant tumors.</p></div><div><h3>Conclusions</h3><p>In this population-wide cohort study, left-sidedness of the primary tumor and the addition of chemotherapy were associated with a longer OS and TTD for regorafenib treatment for mCRC.</p></div>","PeriodicalId":100490,"journal":{"name":"ESMO Gastrointestinal Oncology","volume":"4 ","pages":"Article 100052"},"PeriodicalIF":0.0,"publicationDate":"2024-04-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S294981982400013X/pdfft?md5=00dcd942d92f29c61d3ec7a6b7269081&pid=1-s2.0-S294981982400013X-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140815525","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Age-related outcomes in MSI/dMMR gastrointestinal cancers treated by immune checkpoint inhibitors and toxicity’s impact on efficacy: an immunoMSI cohort study","authors":"L. Mailly-Giacchetti ,&nbsp;R. Colle ,&nbsp;T. Samaille ,&nbsp;D. Lopez-Trabada Ataz ,&nbsp;L. Faucheux ,&nbsp;A. Duval ,&nbsp;T. Andre ,&nbsp;R. Cohen","doi":"10.1016/j.esmogo.2024.100047","DOIUrl":"https://doi.org/10.1016/j.esmogo.2024.100047","url":null,"abstract":"<div><h3>Background</h3><p>Immune-checkpoint inhibitors (ICIs) are the standard of care for microsatellite instability (MSI) metastatic gastrointestinal cancer (mGIC) patients in first- and later-treatment lines. We compared tolerability and efficacy of ICIs in elderly (aged ≥75 years) versus non-elderly MSI mGIC patients and analyzed the correlation between immune-related adverse events (irAEs) and efficacy.</p></div><div><h3>Patients and methods</h3><p>This single-center prospective cohort study included MSI mGIC patients treated with ICIs, excluding chemotherapy. Assessments covered grade ≥3 irAEs and ≥2 endocrine irAEs (E-irAEs).</p></div><div><h3>Results</h3><p>Among 201 patients, 24 were elderly (mean age 75–90 years) and 177 non-elderly (mean age 22-74 years). In the overall population, grade ≥3 irAEs and E-irAEs incidence was 40% with the anti-programmed cell death protein 1 + anti-cytotoxic T lymphocyte-associated antigen 4 and 23% with anti-programmed cell death protein 1 monotherapy (<em>P</em> = 0.011). Treatment combination was administered to 29% of elderly and 40% of non-elderly patients. The incidence of grade ≥3 irAEs and E-irAEs was 37%/29% with monotherapy (<em>P</em> = 0.48) and 57%/39% with combination (<em>P</em> = 0.43) in elderly/non-elderly patients. No significant difference was observed in progression-free survival [hazard ratio (HR) = 1.15, 95% confidence interval (CI) 0.57-2.32, <em>P</em> = 0.7] and OS (HR = 1.61, 95% CI 0.75-3.43, <em>P</em> = 0.25) between elderly and non-elderly. Cox regression analysis with a time-dependent variable showed no survival difference between patients with/without grade ≥3 irAEs and E-irAEs (progression-free survival: HR = 1.19, 95% CI 0.64-2.19, <em>P</em> = 0.59; overall survival: HR = 0.91, 95% CI 0.44-1.92, <em>P</em> = 0.81). A positive association was found, however, between objective response rate and immune treatment-related adverse event occurrence [77%/59%, immune treatment-related adverse event patients/others (<em>P</em> = 0.0012)].</p></div><div><h3>Conclusion</h3><p>This study reveals comparable tolerability and efficacy of ICIs in elderly and non-elderly patients with MSI mGIC. Survival outcomes did not differ significantly between patients with and without grade ≥3 irAEs and E-irAEs.</p></div>","PeriodicalId":100490,"journal":{"name":"ESMO Gastrointestinal Oncology","volume":"4 ","pages":"Article 100047"},"PeriodicalIF":0.0,"publicationDate":"2024-04-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2949819824000086/pdfft?md5=22095c708d9461a88ec4143d6a67f5ef&pid=1-s2.0-S2949819824000086-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140815560","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Role of the microbiome in the development and treatment of gastric cancer: an overview of the biological and clinical landscape","authors":"C.A. Cella ,&nbsp;D. Ciardiello ,&nbsp;L. Gervaso ,&nbsp;H. van Laarhoven ,&nbsp;L. Nezi ,&nbsp;C. Catozzi ,&nbsp;F. Lordick ,&nbsp;E. Smyth ,&nbsp;S. de Pascale ,&nbsp;L. Benini ,&nbsp;V. Carmine ,&nbsp;L. Guidi ,&nbsp;U. Fumagalli Romario ,&nbsp;N. Fazio","doi":"10.1016/j.esmogo.2024.100048","DOIUrl":"https://doi.org/10.1016/j.esmogo.2024.100048","url":null,"abstract":"<div><p>For decades, the stomach was considered a sterile organ, due to the acid environment. However, starting from the discovery of <em>Helicobacter pylori</em>, this concept has progressively refined. By damaging the hydrochloric acid-secreting glands, <em>H. pylori</em> infection primes the progression from acute to chronic inflammation in gastric mucosa resulting in atrophic gastritis, intestinal metaplasia, dysplasia and ultimately gastric cancer (GC). Due to the challenging identification of culturing bacteria, the carcinogenic role of gastric microbial community, other than <em>H. pylori</em>, remains underestimated. More recently, a growing body of evidence has pointed out the dynamism of gastric microbiota as a crucial step for GC development, besides elucidating some additional activity in modulating the efficacy of cancer treatments. In turn, anticancer therapies can shape gastric microbiota with consequent dysbiosis and a potential correlation with drug-related toxicity. In conclusion, the current review aims to deepen the role of gut microbiota as a key factor in gastric disease at multiple levels, from carcinogenesis to the metastatic phase. It also provides novel insights on gastric microbiota as potential target for tailoring multimodal strategies, either surgical or oncological, to finally provide our patients with more individualized treatment options.</p></div>","PeriodicalId":100490,"journal":{"name":"ESMO Gastrointestinal Oncology","volume":"4 ","pages":"Article 100048"},"PeriodicalIF":0.0,"publicationDate":"2024-04-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2949819824000098/pdfft?md5=c0d7f56166d27540f5de4dd136e41015&pid=1-s2.0-S2949819824000098-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140650081","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"HER2-directed therapy following ctDNA-identified ERBB2 amplification in patients with advanced gastroesophageal cancer: exploration of real-world outcomes","authors":"S. Chakrabarti ,&nbsp;L. Bucheit ,&nbsp;J. Saha ,&nbsp;K. Clemens ,&nbsp;R. Barnett ,&nbsp;N. Zhang ,&nbsp;A. Mahipal","doi":"10.1016/j.esmogo.2024.100056","DOIUrl":"https://doi.org/10.1016/j.esmogo.2024.100056","url":null,"abstract":"<div><h3>Background</h3><p>Data on patient outcomes with human epidermal growth factor receptor 2 (HER2)-directed therapy after detection of <em>ERBB2</em> amplification (<em>ERBB2</em> amp) by circulating tumor DNA (ctDNA) are lacking in advanced gastroesophageal adenocarcinoma (aGEA). We report real-world outcomes in aGEA patients who received HER2-directed therapy following ctDNA-identified <em>ERBB2</em> amp.</p></div><div><h3>Materials and methods</h3><p>Real-world evidence was sourced from the GuardantINFORM (Guardant Health) database which includes aggregated health claims and de-identified results from patients undergoing ctDNA testing [Guardant360 (G360)]. Patients with aGEA, <em>ERBB2</em> amp, and one or more claims for treatment after index G360 were included; those with prior HER2-directed therapy were excluded. Real-world time to treatment discontinuation (rwTTD), real-world time to next treatment (rwTTNT), and real-world overall survival (rwOS) were assessed in months. The Cox regression model adjusted for age, gender, and lines of treatment since diagnosis assessed differences in outcomes.</p></div><div><h3>Results</h3><p>We identified 215 patients with <em>ERBB2</em> amp, out of which 135 (63%) received HER2-directed therapy following ctDNA-identified <em>ERBB2</em> amp. rwTTD and rwTTNT were significantly improved in patients receiving HER2-directed therapy compared with those who did not [rwTTD: 5.8 versus 1.9 months, hazard ratio (HR) 0.47, 95% confidence interval (CI) 0.34-0.65, <em>P</em> &lt; 0.01; rwTTNT: 9.4 versus 6.3 months, HR 0.55, 95% CI 0.37-0.81, <em>P</em> &lt; 0.01]. No differences in rwOS were observed (rwOS: not reached versus 22 months, HR 0.67, 95% CI 0.41-1.08, <em>P</em> = 0.10).</p></div><div><h3>Conclusions</h3><p>Detection of <em>ERBB2</em> amp by ctDNA testing is feasible and may confer improved outcomes in patients receiving HER2-directed therapy, presenting an opportunity to increase HER2-directed therapy utilization in patients with aGEA.</p></div>","PeriodicalId":100490,"journal":{"name":"ESMO Gastrointestinal Oncology","volume":"4 ","pages":"Article 100056"},"PeriodicalIF":0.0,"publicationDate":"2024-04-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2949819824000177/pdfft?md5=10e7c8b95f331750200841d73cd351a5&pid=1-s2.0-S2949819824000177-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140641323","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Second-line FOLFOX chemotherapy for patients with advanced biliary tract cancers pretreated with cisplatin/gemcitabine: a systematic review and meta-analysis","authors":"A. Digklia ,&nbsp;D. Arnold ,&nbsp;I.A. Voutsadakis","doi":"10.1016/j.esmogo.2024.100055","DOIUrl":"https://doi.org/10.1016/j.esmogo.2024.100055","url":null,"abstract":"<div><h3>Background</h3><p>Biliary cancers are aggressive carcinomas frequently diagnosed at an advanced stage. Palliative combination systemic therapy provides survival benefits in the first-line setting of advanced and metastatic disease. FOLFOX chemotherapy is one of the few options in the second-line therapy.</p></div><div><h3>Materials and methods</h3><p>The medical literature was searched through the Medline/PubMed and Embase databases to acquire clinical reports or trials of FOLFOX treatment for biliary cancers in the second-line metastatic setting after first-line cisplatin/gemcitabine chemotherapy. Eligible prospective and retrospective studies were reviewed and included in a meta-analysis with overall response rate (ORR), disease control rate (DCR), progression-free survival (PFS), and overall survival (OS) as outcomes of interest.</p></div><div><h3>Results</h3><p>Six clinical studies were eligible and included in the meta-analysis. The ORR with second-line FOLFOX chemotherapy in this population was 10.42% [95% confidence interval (CI) 4.55% to 16.3%]. Two-fifths of the patients had stable disease for a DCR of 50.65% (95% CI 38.4% to 62.9%). The median PFS was 3.03 months (95% CI 1.38-4.09 months) and the median OS was 6.43 months (95% CI 5.43-7.43 months). The main grade 3/4 adverse effects observed in &gt;10% of patients were neutropenia (21.2%) and asthenia/fatigue (10.3%).</p></div><div><h3>Conclusions</h3><p>The meta-analysis observed a moderate efficacy of the FOLFOX combination in this setting. These results may be used as a benchmark to compare gains obtained in this setting with novel treatments, including recently introduced targeted therapies in appropriately selected patients.</p></div>","PeriodicalId":100490,"journal":{"name":"ESMO Gastrointestinal Oncology","volume":"4 ","pages":"Article 100055"},"PeriodicalIF":0.0,"publicationDate":"2024-04-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2949819824000165/pdfft?md5=c8d52ffa2793b1b75e9b284b1ac2b435&pid=1-s2.0-S2949819824000165-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140641299","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Safety and efficacy of perioperative FLOT regimen in Japanese patients with gastric, esophagogastric junction, or esophageal adenocarcinoma: a single-institution experience","authors":"S. Takei ,&nbsp;A. Kawazoe ,&nbsp;A. Jubashi ,&nbsp;M. Komatsu ,&nbsp;K. Sato ,&nbsp;S. Mishima ,&nbsp;D. Kotani ,&nbsp;M. Yura ,&nbsp;N. Sakamoto ,&nbsp;S. Sakashita ,&nbsp;T. Kuwata ,&nbsp;T. Kojima ,&nbsp;T. Fujita ,&nbsp;T. Kinoshita ,&nbsp;K. Shitara","doi":"10.1016/j.esmogo.2024.100050","DOIUrl":"https://doi.org/10.1016/j.esmogo.2024.100050","url":null,"abstract":"<div><h3>Background</h3><p>Although the common treatment strategy for localized gastric cancer in Japan is gastrectomy followed by adjuvant chemotherapy, several randomized studies in non-Japanese populations have established perioperative chemotherapy as the standard treatment of localized gastric or gastroesophageal junction adenocarcinoma. Therefore, we have implemented this strategy in our institution.</p></div><div><h3>Patients and methods</h3><p>We retrospectively reviewed the medical records of patients with resectable gastric cancer, gastroesophageal junction cancer, and esophageal adenocarcinoma who had received perioperative FLOT (5-fluorouracil plus docetaxel plus oxaliplatin plus leucovorin) from February 2020 to February 2023.</p></div><div><h3>Results</h3><p>In this study, a total of 91 patients were analyzed, with a median age of 70 years (range: 29-82). At the time of diagnosis, 83 patients (91.2%) had T3 or higher-grade primary lesions, and 85 (93.4%) had lymph node metastasis. A total of 10 patients had resection before completing four cycles of preoperative chemotherapy, and 77 of 91 (84.6%) completed four cycles with 74 of them receiving radical resection. Among the 84 patients who had radical resection after FLOT, 82 (97.6%) achieved R0 resection, including 8 (9.5%) with a pathological complete response. After resection, 60 patients (65.9%) received at least one cycle of post-operative FLOT, and 47 (51.6%) completed eight cycles of FLOT treatment. Chemotherapy-related adverse events of grade 3 or higher occurred during the pre- and post-operative FLOT in 60 patients (65.9%), including leukopenia (30.8%), neutropenia (50.5%), febrile neutropenia (5.5%), and anorexia (7.7%). No treatment-related deaths occurred.</p></div><div><h3>Conclusions</h3><p>These findings were comparable to those in the pivotal FLOT 4 trial, suggesting acceptable feasibility of the FLOT regimen in Japanese clinical practice.</p></div>","PeriodicalId":100490,"journal":{"name":"ESMO Gastrointestinal Oncology","volume":"4 ","pages":"Article 100050"},"PeriodicalIF":0.0,"publicationDate":"2024-04-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2949819824000116/pdfft?md5=9d254b4410a3bc07ae52e33909ef7b25&pid=1-s2.0-S2949819824000116-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140604722","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Benefits from early trial involvement in metastatic colorectal cancer: outcomes from the phase I unit at the Sarah Cannon Research Institute UK","authors":"R. Woodford ,&nbsp;S. Luo ,&nbsp;E. Ignatova ,&nbsp;A. Cammarota ,&nbsp;J. Choy ,&nbsp;R. Grochot ,&nbsp;A. Williams ,&nbsp;T. Arkenau ,&nbsp;E. Fontana","doi":"10.1016/j.esmogo.2024.100054","DOIUrl":"https://doi.org/10.1016/j.esmogo.2024.100054","url":null,"abstract":"<div><h3>Background</h3><p>Metastatic colorectal cancer (CRC) is associated with poor overall survival (OS) and limited activity of approved therapeutics following two standard lines of chemotherapy. Participation in phase I trials could offer an alternative treatment option; however, benefit from participation remains unclear.</p></div><div><h3>Materials and methods</h3><p>Medical records of patients enrolled in phase I trials at the Sarah Cannon Research Institute UK between October 2011 and July 2022 were reviewed. Patients who had received at least one dose of investigational therapy were included. Patient demographics, tumor histopathologic and molecular characteristics, clinical outcomes, including objective response rate (ORR) and clinical benefit rate (CBR), and drug details were assessed using descriptive statistics and univariable and multivariable analyses.</p></div><div><h3>Results</h3><p>Of 1796 patients screened for phase I trials, 80 CRC patients from 31 phase I trials of 27 distinct investigational agents were included in the analysis. Overall, 53.8% were men, median age was 59 years (range 31-80 years) and median number of prior lines was 2 (range 1-6 prior lines). Median follow-up was 7 months (range 0.3-70.8 months). ORR was 7% [95% confidence interval (CI) 3.3% to 15.7%] and CBR 47% (95% CI 40.3% to 62%) across all trials. Median OS was 16.8 months (95% CI 8.8-22.0 months). The 12-month survival rate was 58%. Subgroup assessment demonstrated better outcomes for subjects receiving immunotherapies, while multivariable logistical regression demonstrated increased OS for surgery on the primary tumor [hazard ratio (HR) 0.05 (95% CI 0.00-0.69), <em>P</em> = 0.03], low lymphocyte/monocyte ratio [HR 0.45 (95% CI 0.20-0.95), <em>P</em> = 0.04] and left-sidedness [HR 0.10 (95% CI 0.14-0.70), <em>P</em> = 0.02].</p></div><div><h3>Conclusions</h3><p>Phase I trials may provide relevant benefits for patients with refractory CRC with comparable survival to third-line therapies. Early consideration of phase I involvement may provide expedited access to potential future standard-of-care options.</p></div>","PeriodicalId":100490,"journal":{"name":"ESMO Gastrointestinal Oncology","volume":"4 ","pages":"Article 100054"},"PeriodicalIF":0.0,"publicationDate":"2024-04-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2949819824000153/pdfft?md5=01a3e34fd6a3d76cc7ae61bf66a08e71&pid=1-s2.0-S2949819824000153-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140604721","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}