Targeted Oncology最新文献

{"title":"Enfortumab Vedotin Following Platinum Chemotherapy and Avelumab Maintenance in Patients with Metastatic Urothelial Carcinoma: A Retrospective Data from the ARON-2^EV Study.","authors":"Ondřej Fiala, Francesco Massari, Umberto Basso, Patrizia Giannatempo, Enrique Grande, Sebastiano Buti, Zin W Myint, Ugo De Giorgi, Renate Pichler, Francesco Grillone, Yüksel Ürün, Fabio Calabrò, Maria T Bourlon, Luca Galli, Ravindran Kanesvaran, Giandomenico Roviello, Jakub Kucharz, Mimma Rizzo, Se Hoon Park, Linda Cerbone, Emmanuel Seront, Carlo Messina, Javier Molina-Cerrillo, Daniele Santini, Akihiro Yano, Lorena Incorvaia, Martina Catalano, Alvaro Pinto, Luigi Formisano, Andrey Soares, Gaetano Facchini, Giuseppe Fornarini, Alexandr Poprach, Sara Elena Rebuzzi, Cecilia Nasso, Gian Paolo Spinelli, Martin Angel, Marco Stellato, Deniz Tural, Gaetano Aurilio, Ilana Epstein, Francesco Carrozza, Fernando Sabino Marques Monteiro, Giovanni Benedetti, Tomáš Büchler, Cinzia Ortega, Roubini Zakopoulou, Nicola Battelli, Camillo Porta, Joaquin Bellmunt, Shilpa Gupta, Matteo Santoni","doi":"10.1007/s11523-024-01099-0","DOIUrl":"10.1007/s11523-024-01099-0","url":null,"abstract":"<p><strong>Background: </strong>Enfortumab vedotin (EV) has been approved for the treatment of patients with locally advanced/metastatic urothelial carcinoma (la/mUC) who previously received platinum-based chemotherapy followed by immune checkpoint inhibitors. However, the pivotal clinical trials did not include patients previously treated with avelumab maintenance therapy.</p><p><strong>Objective: </strong>The aim of the present retrospective analysis was to assess the effectiveness of EV following avelumab in patients with mUC enrolled in the ARON-2^EV study.</p><p><strong>Patients and methods: </strong>The study included 182 patients with mUC treated with EV following avelumab maintenance. The primary objective was to assess clinical outcomes, including progression-free survival (PFS), overall survival (OS), overall response rate (ORR), and duration of response (DoR). Statistical analysis involved Fisher exact test, Kaplan-Meier method, log-rank test, and univariate/multivariate Cox proportional hazard regression models.</p><p><strong>Results: </strong>Median OS and PFS were 12.7 (95% CI 10.2-14.1) and 7.9 (95% CI 6.4-9.9) months, respectively. Complete response (CR) was achieved in 5% and partial response (PR) in 34% of patients, with an ORR of 39%. The DoR in patients who achieved CR/PR was 10.9 months (95% CI 8.1-11.4). The incidence of grade ≥ 3 peripheral neuropathy and skin rash was 9%, followed by 8% of grade ≥ 3 diarrhea and 4% of grade ≥ 3 hyperglycemia.</p><p><strong>Conclusions: </strong>The results of our large international retrospective study confirm the effectiveness of EV and endorse its use in the population of patients with mUC treated with EV following the frontline platinum-based chemotherapy and subsequent maintenance treatment with avelumab.</p>","PeriodicalId":22195,"journal":{"name":"Targeted Oncology","volume":" ","pages":"905-915"},"PeriodicalIF":4.4,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11557677/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142362122","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":"Acknowledgement to Referees.","authors":"","doi":"10.1007/s11523-024-01112-6","DOIUrl":"10.1007/s11523-024-01112-6","url":null,"abstract":"","PeriodicalId":22195,"journal":{"name":"Targeted Oncology","volume":" ","pages":"819-822"},"PeriodicalIF":4.4,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142591141","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":"Impact of Etiology on Efficacy Outcomes with Atezolizumab Plus Bevacizumab in Patients with Advanced Hepatocellular Carcinoma: A Multinational Retrospective Analysis in Asia-Pacific.","authors":"Sejin Kim, Suat Ying Lee, Jaekyung Cheon, Hyung-Don Kim, Young Gyu Park, Joycelyn Jie Xin Lee, Min-Hee Ryu, Baek-Yeol Ryoo, David Tai, Changhoon Yoo","doi":"10.1007/s11523-024-01103-7","DOIUrl":"10.1007/s11523-024-01103-7","url":null,"abstract":"<p><strong>Background: </strong>Atezolizumab-bevacizumab is a standard first-line treatment for unresectable hepatocellular carcinoma (uHCC). Given the diversity in HCC etiology and its potential impact on the tumor microenvironment, understanding how different liver disease etiologies affect treatment efficacy is important.</p><p><strong>Objective: </strong>We assessed the influence of liver disease etiology on the efficacy of atezolizumab-bevacizumab and evaluated changes in liver function during treatment with atezolizumab-bevacizumab.</p><p><strong>Patients and methods: </strong>This study included 390 patients with uHCC treated with first-line atezolizumab-bevacizumab from Asan Medical Center, South Korea, and National Cancer Centre Singapore, Singapore from July 2016 to March 2023. Patients were classified to viral, metabolic dysfunction-associated liver disease (MASLD) and nonviral/non-MASLD groups. Albumin-bilirubin (ALBI) scores were recorded at baseline and every two cycles up to cycle six and at the time of disease progression.</p><p><strong>Results: </strong>The majority of patients presented with viral etiologies (74.1%), and 17.2% had MASLD. Across etiological groups (viral versus MASLD versus nonviral/non-MASLD) no significant differences in objective response rate (23.2% versus 29.9% versus 23.5%, respectively; p = 0.515), progression-free survival (median 5.4 versus 7.7 versus 6.0 months; p = 0.320), and overall survival (18.1 versus 18.9 versus 14.4 months; p = 0.400) were observed. Among the patients with disease progression, ALBI scores at the time of progression were significantly higher than at baseline. Subsequent therapy was administered significantly less often to patients with ALBI grade 3 at disease progression compared with those with ALBI grades 1 or 2 (48.4% versus 78.8%, p = 0.002) CONCLUSIONS: Atezolizumab-bevacizumab demonstrates consistent efficacy regardless of HCC etiology, supporting its use as a first-line treatment across diverse patient populations. Liver function assessments remain crucial for managing therapy and predicting outcomes.</p>","PeriodicalId":22195,"journal":{"name":"Targeted Oncology","volume":" ","pages":"917-923"},"PeriodicalIF":4.4,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142366624","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":"Real-Life Experience with Entrectinib in Neurotrophic Tyrosine Receptor Kinase Fusion-Positive Solid Tumors: A Multicenter Retrospective Trial.","authors":"Feride Yılmaz, Serkan Yaşar, Nil Molinas Mandel, Turgut Kaçan, Melek Özdemir, Gamze Gököz Doğu, Nilay Şengül, Nezih Meydan, Fatma Buğdaycı Başal, Pınar Kubilay Tolunay, Melda Berber Hamamcı, Oğuz Salih Dinçer, Aykut Bahçeci, Leyla Özer, Miraç Ajredini, Önder Kırca, Özlem Yersal, Orçun Can, Meral Günaldı, Gökhan Demir, Şuayib Yalçın","doi":"10.1007/s11523-024-01095-4","DOIUrl":"10.1007/s11523-024-01095-4","url":null,"abstract":"<p><strong>Background: </strong>Neurotrophic tyrosine receptor kinase (NTRK) gene fusions represent rare somatic mutations in many types of cancer and have enabled the use of promising targeted therapies. In clinical studies, increased response rates to tropomyosin receptor kinase inhibitors have been demonstrated in NTRK fusion-positive cancer types; however, real-world experiences on these targeted agents are scarce.</p><p><strong>Objective: </strong>We evaluated the clinical characteristics and treatment responses of NTRK fusion-positive patients who received entrectinib treatment within the scope of an early access program in Turkey.</p><p><strong>Patients and methods: </strong>This multicenter, retrospective analysis involved 17 patients with solid tumors harboring NTRK fusions or rearrangements from 14 oncology centers between June 2019 and 31 March 2024. Demographic and clinical data were obtained via retrospective review of medical records with a cutoff date of 31 March 2024.</p><p><strong>Results: </strong>The median age at diagnosis of the patients in our study was 42 [interquartile range (IQR) 33-60] years. Nine different types of solid tumors were diagnosed in these patients. The most common NTRK gene rearrangements involved NTRK1 (n = 8), followed by NTRK3 (n = 7). The median duration of entrectinib usage was 6.9 (IQR 3.1-16.1) months. Dose reductions due to side effects were performed in four patients: two due to leukopenia, one due to visual disturbance, and one due to troponin elevation. Leukopenia was the most commonly observed side effect. The objective response rate (ORR) was 35.3% (95% confidence interval (CI) 14.2-62.7), with complete response (CR) achieved in four patients. The duration of response (DOR) in patients who responded after initiating entrectinib was 9.8 (95% CI 0-30.7) months, the median overall survival (mOS) in all patients was 20.8 (95% CI 0-48.5) months, and the time-to-treatment failure (TTF) was 6.4 (95% CI 0-13.5) months.</p><p><strong>Conclusions: </strong>In this retrospective study, we aimed to obtain real-world data concerning the use of entrectinib in patients with solid tumors harboring NTRK fusion genes. Although our findings are partially similar to the results of clinical studies, prospective studies in larger patient groups with more diverse tumor types and different demographic characteristics are needed to confirm the findings.</p>","PeriodicalId":22195,"journal":{"name":"Targeted Oncology","volume":" ","pages":"957-964"},"PeriodicalIF":4.4,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142354332","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":"Taiwan Nationwide Study of First-Line ALK-TKI Therapy in ALK-Positive Lung Adenocarcinoma.","authors":"Zhe-Rong Zheng, Jia-Jun Wu, Chun-Ju Chiang, Tzu-I Chen, Kun-Chieh Chen, Cheng-Hsiang Chu, Sheng-Yi Lin, Sung-Liang Yu, Wen-Chung Lee, Tsang-Wu Liu, Gee-Chen Chang","doi":"10.1007/s11523-024-01104-6","DOIUrl":"10.1007/s11523-024-01104-6","url":null,"abstract":"<p><strong>Background: </strong>The clinical outcomes of patients with anaplastic lymphoma kinase-positive (ALK+) advanced lung adenocarcinoma vary according to real-world data.</p><p><strong>Objective: </strong>In this study, we aimed to investigate the treatment discontinuation (TTD) and overall survival (OS) of patients with ALK+ advanced lung adenocarcinoma treated with first-line ALK-TKIs in Taiwan.</p><p><strong>Patients and methods: </strong>This retrospective study evaluated all advanced lung adenocarcinoma patients registered in the National Taiwan Cancer Registry from 2017 to 2020 who had ALK rearrangement and received ALK-TKI treatment, using data from Taiwan's National Health Insurance Research Database (NHIRD). The TKI treatment sequences were classified into first generation (G1: crizotinib), second generation (G2: ceritinib, alectinib, brigatinib), and third generation (G3: lorlatinib).</p><p><strong>Results: </strong>A total of 587 patients were analyzed, with a median age of 60.0 years, 91 (15.5%) aged ≥ 74 years, 293 (49.9%) female, 397 (67.6%) never smoked, and 534 (91.0%) with stage IV disease. Patients who received next-generation ALK-TKIs during the treatment course had longer median time to ALK-TKI TTD and OS. The TTD of the G1, G1+2, G1+2+3, G2, and G2+3 groups was 7.5 (5.4-11.1), 40.6 (29.4-not calculated (NC)), 50.3 (41.3-NC), 34.3 (29.2-43.0), and 36.3 (22.4-NC) months, respectively (p < 0.001). The median OS of the patients in the G1, G1+2, G1+2+3, G2, and G2+3 groups was 10.6 (7.5-14.6), not reached (NR) (NC-NC), NR (NC-NC), 43.0 (36.3-NC), and NR (30.3-NC) months, respectively (p < 0.001). Compared with treatment with crizotinib alone, the multivariate analysis revealed that treatment with next-generation TKIs was independently associated with longer TTD (G1+2 (hazard ratio (HR), 0.24; 95% CI 0.17-0.33; p < 0.001), G1+2+3 or G1+3 (HR, 0.17; 95% confidence interval (CI), 0.10-0.28; p < 0.001), G2 (HR, 0.26; 95% CI 0.19-0.36; p < 0.001), and G2+3 (HR, 0.25; 95% CI 0.14-0.44; p < 0.001)) and median OS (G12 (HR, 0.24; 95% CI 0.17-0.35; p < 0.001), G1+2+3 or G1+3 (HR, 0.09; 95% CI 0.04-0.21; p < 0.001), G2 (HR, 0.22; 95% CI 0.15-0.31; p < 0.001), and G2+3 (HR, 0.20; 95% CI 0.10-0.42; p < 0.001)).</p><p><strong>Conclusions: </strong>For patients with ALK+ NSCLC, treatments including next-generation ALK-TKIs were independently associated with longer survival outcomes.</p>","PeriodicalId":22195,"journal":{"name":"Targeted Oncology","volume":" ","pages":"941-955"},"PeriodicalIF":4.4,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142401405","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":"Adavosertib in Combination with Olaparib in Patients with Refractory Solid Tumors: An Open-Label, Dose-Finding, and Dose-Expansion Phase Ib Trial.","authors":"Erika P Hamilton, Gerald S Falchook, Judy S Wang, Siqing Fu, Amit M Oza, Esteban Rodrigo Imedio, Sanjeev Kumar, Lone Ottesen, Ganesh M Mugundu, Elza C de Bruin, Mark J O'Connor, Suzanne F Jones, David R Spigel, Bob T Li","doi":"10.1007/s11523-024-01102-8","DOIUrl":"10.1007/s11523-024-01102-8","url":null,"abstract":"<p><strong>Background: </strong>Adavosertib is a first-in-class, selective small-molecule inhibitor of Wee1. Olaparib is an inhibitor of poly(ADP-ribose) polymerase (PARP). Preclinical data suggest that adavosertib enhances the antitumor effect of PARP inhibitors.</p><p><strong>Objective: </strong>The safety, tolerability, and efficacy of adavosertib plus olaparib were evaluated in patients with refractory solid tumors to define the maximum tolerated dose (MTD) and recommended phase II dose (RP2D).</p><p><strong>Patients and methods: </strong>Eligible patients in part A (dose finding) had a refractory solid tumor for which there is no established treatment and had received ≥ 1 prior course of systemic therapy; in part B (dose expansion), patients had platinum-sensitive extensive-stage or relapsed small-cell lung cancer (SCLC). Patients received adavosertib [once (qd) or twice daily (bid)] for 3 consecutive days with 4 days off treatment (3/4), or 5 consecutive days with 2 days off (5/2), plus olaparib (bid) for 14 or 21 days of a 21-day cycle.</p><p><strong>Results: </strong>A total of 130 patients were enrolled in the study, 120 in part A and 10 in part B. The MTD for adavosertib bid was 175 mg (days 1-3, 8-10/21-day cycle) plus continuous olaparib 200 mg bid; the once-daily MTD (and RP2D) was adavosertib 200 mg (days 1-3, 8-10/21-day cycle) plus continuous olaparib 200 mg bid. In the MTD/RP2D cohort, one patient (7%) experienced a dose-limiting toxicity (DLT) of thrombocytopenia. The most common treatment-related adverse events (TRAEs) in the cohorts in which MTD/RP2D for bid dosing and RP2D for qd dosing were determined were fatigue (64.3% and 15.4%, respectively), diarrhea (42.9% and 30.8%), decreased appetite (35.7% and 23.1%), nausea (35.7% and 15.4%), and anemia (35.7% and 38.5%). In the SCLC dose-expansion cohort, TRAEs occurred in eight patients (88.9%), including thrombocytopenia (66.7%) and anemia (55.6%). In part A, objective response rate (ORR) was 14.8% [95% confidence interval (CI) 8.7-22.9] overall; for the cohorts in which MTD/RP2D for bid dosing and RP2D for qd dosing were determined, ORR was 30.8% (9.1-61.4) and 9.1% (0.2-41.3), respectively. ORR was 11.1% [95% CI 0.3-48.2; one partial response (PR)], disease control rate was 22.2% (2.8-60.0; one PR, one stable disease), and median progression-free survival was 1.5 months (1.3-4.2) in the SCLC dose-expansion cohort.</p><p><strong>Conclusions: </strong>Adverse events and DLTs observed in the bid MTD and once-daily MTD/RP2D dosing schedules were manageable and consistent with known adavosertib and olaparib safety profiles. Limited antitumor activity was observed with adavosertib plus olaparib combination therapy.</p><p><strong>Trial registration: </strong>ClinicalTrials.gov, NCT02511795 (registration: 28 July 2015).</p>","PeriodicalId":22195,"journal":{"name":"Targeted Oncology","volume":" ","pages":"879-892"},"PeriodicalIF":4.4,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11557630/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142565214","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":"Pancreatitis in Patients with Cancer Receiving Immune Checkpoint Inhibitors: A Systematic Review and Meta-analysis.","authors":"Mako Koseki, Yoshito Nishimura, Evelyn Elias, Jonathan Estaris, Fnu Chesta, Kensuke Takaoka, Theresa Shao, Nobuyuki Horita, Yu Fujiwara","doi":"10.1007/s11523-024-01098-1","DOIUrl":"10.1007/s11523-024-01098-1","url":null,"abstract":"<p><strong>Background: </strong>Immune checkpoint inhibitors (ICIs) occasionally cause immune-related adverse events (AEs), which pose challenges to the continuation of treatment. Although ICIs are widely used in patients with cancer, studies reporting immune-mediated pancreatitis remain scarce.</p><p><strong>Objectives: </strong>We performed a systematic review and meta-analysis to address current knowledge gaps and provide clinical guidance for ICI-associated pancreatitis and lipase elevation.</p><p><strong>Patients and methods: </strong>We searched PubMed/Medline, Embase, and Web of Science for phase 3 randomized controlled trials (RCTs) evaluating ICIs. The incidence of any-grade and grade 3-5 pancreatitis/lipase elevation was calculated. Then, we performed a random-effect model meta-analysis to pool the odds ratios (ORs) of these outcomes using RCTs evaluating the addition of an ICI to systemic therapy to assess the effect of ICIs on pancreatic AEs. A systematic review of the treatment of ICI-related pancreatitis was also conducted.</p><p><strong>Results: </strong>The incidence analysis included 81 articles (79 RCTs) comprising 36,871 patients. The incidence of treatment-related pancreatitis was 0.68% (any-grade) and 0.32% (grade 3-5). Meta-analysis revealed that the addition of ICI therapy significantly increased any-grade (OR 2.12, 95% confidence interval [CI] 1.45-3.11, p < 0.001) and grade 3-5 pancreatitis (OR 1.76, 95% CI 1.01-3.08, p < 0.05) with low heterogeneity among ICI subtype subgroups (any-grade: I² = 0%, p = 0.99; grade 3-5: I² = 0%, p = 0.63). In analysis of treatment outcome among 146 patients from 53 articles, glucocorticoids were used in 80.6% (n = 108/134) and ICIs were discontinued in 76.5% (n = 101/132; permanent discontinuation: 62.5% [n = 35/56]).</p><p><strong>Conclusions: </strong>The overall rate of pancreatitis appears low, but the addition of ICI therapy significantly increased the incidence of pancreatitis. These findings provide insight into the incidence and treatment of pancreatitis associated with ICIs.</p>","PeriodicalId":22195,"journal":{"name":"Targeted Oncology","volume":" ","pages":"867-877"},"PeriodicalIF":4.4,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142401404","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 Epidemiology of Biliary Tract Cancer and Associated Prevalence of MDM2 Amplification: A Targeted Literature Review.","authors":"Jeremy David Kratz, Alyssa Barchet Klein, Courtney Beth Gray, Angela Märten, Hanna-Liisa Vilu, Jennifer Francesca Knight, Alexandra Kumichel, Makoto Ueno","doi":"10.1007/s11523-024-01086-5","DOIUrl":"10.1007/s11523-024-01086-5","url":null,"abstract":"<p><p>Biliary tract cancer (BTC) is a rare and aggressive malignancy that is anatomically classified as gallbladder cancer (GBC), extra- and intra-hepatic cholangiocarcinoma (eCCA and iCCA) and ampullary cancer (AC). BTC is often diagnosed at an advanced stage when treatment options are limited and patients have a poor prognosis, so the identification of new drug targets is of critical importance. BTC is molecularly diverse and harbours different therapeutically actionable biomarkers, including mouse double minute 2 homolog (MDM2), which is currently being investigated as a drug target. The aim of this targeted review was to evaluate and synthesise evidence on the epidemiology of BTC and its subtypes in different geographic regions and on the frequency of MDM2 amplifications in BTC tumours. Epidemiological studies (N = 33) consistently demonstrated high incidence rates in South and Central Asia for BTC overall (up to 9.00/100,000) and for all subtypes, with much lower rates in Europe and the US. Among the different types of BTC, the highest global incidence was observed for CCA, mainly driven by iCCA (1.4/100,000), followed by GBC (1.2/100,000) and AC (0.18-0.93 per 100,000). Studies of MDM2 in BTC (N = 19) demonstrated variable frequency of MDM2 amplification according to subtype, with consistently high MDM2 amplification rates in GBC (up to 17.5%), and lower rates in CCA (up to 4.4%). The results from this literature review highlight the geographic heterogeneity of BTC and the need for standardised clinicopathologic assessment and reporting to allow cross-study comparisons.</p>","PeriodicalId":22195,"journal":{"name":"Targeted Oncology","volume":" ","pages":"833-844"},"PeriodicalIF":4.4,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11557622/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142296036","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":"Risk and Benefit for Basket Trials in Oncology: A Systematic Review and Meta-Analysis.","authors":"Katarzyna Klas, Karolina Strzebonska, Lucja Zaborowska, Tomasz Krawczyk, Alicja Włodarczyk, Urszula Bąk-Kuchejda, Maciej Polak, Simon Van Wambeke, Marcin Waligora","doi":"10.1007/s11523-024-01107-3","DOIUrl":"https://doi.org/10.1007/s11523-024-01107-3","url":null,"abstract":"<p><strong>Background: </strong>Oncology research is increasingly adopting new clinical trial models that implement the concept of precision medicine. One of these is the basket clinical trial design. Basket clinical trials allow new treatments to be evaluated across multiple tumor types. Patients recruited to basket clinical trials share certain molecular characteristics of their cancer that are predictive of clinical benefit from the experimental treatment.</p><p><strong>Objective: </strong>Our aim was to describe the risks and benefits of basket clinical trials in oncology.</p><p><strong>Methods: </strong>Our study was prospectively registered in PROSPERO (CRD42023406401). We systematically searched PubMed, Embase, and ClinicalTrials.gov for reports of basket clinical trials in oncology published between 1 January, 2001, and 14 June, 2023. We measured the risk by treatment-related adverse events (grades 3, 4, and 5), and the benefit by objective response rate. We also extracted and analyzed data on progression-free survival and overall survival. When possible, data were meta-analyzed.</p><p><strong>Results: </strong>We included 126 arms of 75 basket clinical trials accounting for 7659 patients. The pooled objective response rate was 18.0% (95% confidence interval [CI] 14.8-21.1). The rate of treatment-related death was 0.7% (95% CI 0.4-1.0), while 30.4% (95% CI 24.2-36.7) of patients experienced grade 3/4 drug-related toxicity. The median progression-free survival was 3.1 months (95% CI 2.6-3.9), and the median overall survival was 8.9 months (95% CI 6.7-10.2).</p><p><strong>Conclusions: </strong>Our results provide an empirical basis for communicating about the risks and benefits of basket clinical trials and for refining new models of clinical trials applied in precision medicine.</p>","PeriodicalId":22195,"journal":{"name":"Targeted Oncology","volume":" ","pages":""},"PeriodicalIF":4.4,"publicationDate":"2024-10-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142508407","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":"Correction: Ivosidenib: A Review in Advanced Cholangiocarcinoma.","authors":"James E Frampton","doi":"10.1007/s11523-024-01106-4","DOIUrl":"https://doi.org/10.1007/s11523-024-01106-4","url":null,"abstract":"","PeriodicalId":22195,"journal":{"name":"Targeted Oncology","volume":" ","pages":""},"PeriodicalIF":4.4,"publicationDate":"2024-10-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142508406","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}